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  • Articles  (18,506)
  • Elsevier  (10,037)
  • National Academy of Sciences  (3,915)
  • American Association for the Advancement of Science (AAAS)  (2,384)
  • Oxford University Press  (1,747)
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  • International Union of Crystallography
  • 2020-2023
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  • 1980-1984
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  • Articles  (18,506)
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  • 2020-2023
  • 2000-2004  (15,986)
  • 1980-1984
  • 1965-1969  (2,520)
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  • 1
    Electronic Resource
    Electronic Resource
    CORTICAL NEURONAL MIGRATION MUTANTS SUGGEST SEPARATE BUT INTERSECTING PATHWAYS (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 593-618 
    Details
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: During brain development, neurons migrate great distances from proliferative zones to generate the cortical gray matter. A series of studies has identified genes that are critical for migration and targeting of neurons to specific brain regions. These genes encode three basic groups of proteins and produce three distinct phenotypes. The first group encodes cytoskeletal molecules and produces graded and dosage-dependent effects, with a significant amount of functional redundancy. This group also appears to play important roles during the initiation and ongoing progression of neuronal movement. The second group encodes signaling molecules for which homozygous mutations lead to an inverted cortex. In addition, this group is responsible for movement of neurons through anatomic boundaries to specific cortical layers. The third group encodes enzymatic regulators of glycosylation and appears to delineate where neuronal migration will arrest. There is significant cross-talk among these different groups of molecules, suggesting possible points of pathway convergence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.20.082503.103047
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  • 2
    Electronic Resource
    Electronic Resource
    FUNDAMENTALS OF PLANARIAN REGENERATION (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 725-757 
    Details
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The principles underlying regeneration in planarians have been explored for over 100 years through surgical manipulations and cellular observations. Planarian regeneration involves the generation of new tissue at the wound site via cell proliferation (blastema formation), and the remodeling of pre-existing tissues to restore symmetry and proportion (morphallaxis). Because blastemas do not replace all tissues following most types of injuries, both blastema formation and morphallaxis are needed for complete regeneration. Here we discuss a proliferative cell population, the neoblasts, that is central to the regenerative capacities of planarians. Neoblasts may be a totipotent stem-cell population capable of generating essentially every cell type in the adult animal, including themselves. The population properties of the neoblasts and their descendants still await careful elucidation. We identify the types of structures produced by blastemas on a variety of wound surfaces, the principles guiding the reorganization of pre-existing tissues, and the manner in which scale and cell number proportions between body regions are restored during regeneration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.20.010403.095114
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  • 3
    Electronic Resource
    Electronic Resource
    MEMBRANE TRAFFICKING IN PLANTS (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 481-504 
    Details
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Plant membrane trafficking shares many features with other eukaryotic organisms, including the machinery for vesicle formation and fusion. However, the plant endomembrane system lacks an ER-Golgi intermediate compartment, has numerous Golgi stacks and several types of vacuoles, and forms a transient compartment during cell division. ER-Golgi trafficking involves bulk flow and efficient recycling of H/KDEL-bearing proteins. Sorting in the Golgi stacks separates bulk flow to the plasma membrane from receptor-mediated trafficking to the lytic vacuole. Cargo for the protein storage vacuole is delivered from the endoplasmic reticulum (ER), cis-Golgi, and trans-Golgi. Endocytosis includes recycling of plasma membrane proteins from early endosomes. Late endosomes appear identical with the multivesiculate prevacuolar compartment that lies on the Golgi-vacuole trafficking pathway. In dividing cells, homotypic fusion of Golgi-derived vesicles forms the cell plate, which expands laterally by targeted vesicle fusion at its margin, eventually fusing with the plasma membrane.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.20.082503.103057
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  • 4
    Electronic Resource
    Electronic Resource
    DORSAL-VENTRAL PATTERNING AND NEURAL INDUCTION IN XENOPUS EMBRYOS (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 285-308 
    Details
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: We review the current status of research in dorsal-ventral (D-V) patterning in vertebrates. Emphasis is placed on recent work on Xenopus, which provides a paradigm for vertebrate development based on a rich heritage of experimental embryology. D-V patterning starts much earlier than previously thought, under the influence of a dorsal nuclear -Catenin signal. At mid-blastula two signaling centers are present on the dorsal side: The prospective neuroectoderm expresses bone morphogenetic protein (BMP) antagonists, and the future dorsal endoderm secretes Nodal-related mesoderm-inducing factors. When dorsal mesoderm is formed at gastrula, a cocktail of growth factor antagonists is secreted by the Spemann organizer and further patterns the embryo. A ventral gastrula signaling center opposes the actions of the dorsal organizer, and another set of secreted antagonists is produced ventrally under the control of BMP4. The early dorsal -Catenin signal inhibits BMP expression at the transcriptional level and promotes expression of secreted BMP antagonists in the prospective central nervous system (CNS). In the absence of mesoderm, expression of Chordin and Noggin in ectoderm is required for anterior CNS formation. FGF (fibroblast growth factor) and IGF (insulin-like growth factor) signals are also potent neural inducers. Neural induction by anti-BMPs such as Chordin requires mitogen-activated protein kinase (MAPK) activation mediated by FGF and IGF. These multiple signals can be integrated at the level of Smad1. Phosphorylation by BMP receptor stimulates Smad1 transcriptional activity, whereas phosphorylation by MAPK has the opposite effect. Neural tissue is formed only at very low levels of activity of BMP-transducing Smads, which require the combination of both low BMP levels and high MAPK signals. Many of the molecular players that regulate D-V patterning via regulation of BMP signaling have been conserved between Drosophila and the vertebrates.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.20.011403.154124
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  • 5
    Electronic Resource
    Electronic Resource
    NUCLEAR RECEPTORS IN MACROPHAGE BIOLOGY: At the Crossroads of Lipid Metabolism and Inflammation (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 455-480 
    Details
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Macrophages are essential modulators of lipid metabolism and the innate immune system. Lipid and inflammatory pathways induced in activated macrophages are central to the pathogenesis of human diseases including atherosclerosis. Recent work has shown that expression of genes involved in lipid uptake and cholesterol efflux in macrophages is controlled by peroxisome proliferator-activated receptors (PPARs) and liver X receptors (LXRs). Other studies have implicated these same receptors in the modulation of macrophage inflammatory gene expression. Together, these observations position PPARs and LXRs at the crossroads of lipid metabolism and inflammation and suggest that these receptors may serve to integrate these pathways in the control of macrophage gene expression. In this review, we summarize recent work that has advanced our understanding of the roles of PPARs and LXRs in macrophage biology and discuss the implication of these results for cardiovascular physiology and disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.20.012103.134432
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  • 6
    Electronic Resource
    Electronic Resource
    BI-DIRECTIONAL PROTEIN TRANSPORT BETWEEN THE ER AND GOLGI (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 87-123 
    Details
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The endoplasmic reticulum (ER) and the Golgi comprise the first two steps in protein secretion. Vesicular carriers mediate a continuous flux of proteins and lipids between these compartments, reflecting the transport of newly synthesized proteins out of the ER and the retrieval of escaped ER residents and vesicle machinery. Anterograde and retrograde transport is mediated by distinct sets of cytosolic coat proteins, the COPII and COPI coats, respectively, which act on the membrane to capture cargo proteins into nascent vesicles. We review the mechanisms that govern coat recruitment to the membrane, cargo capture into a transport vesicle, and accurate delivery to the target organelle.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.20.010403.105307
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  • 7
    Electronic Resource
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    ASYMMETRIC CELL DIVISION IN C. ELEGANS: Cortical Polarity and Spindle Positioning (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 427-453 
    Details
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The one-cell Caenorhabditis elegans embryo divides asymmetrically into a larger and smaller blastomere, each with a different fate. How does such asymmetry arise? The sperm-supplied centrosome establishes an axis of polarity in the embryo that is transduced into the establishment of anterior and posterior cortical domains. These cortical domains define the polarity of the embryo, acting upstream of the PAR proteins. The PAR proteins, in turn, determine the subsequent segregation of fate determinants and the plane of cell division. We address how cortical asymmetry could be established, relying on data from C. elegans and other polarized cells, as well as from applicable models. We discuss how cortical polarity influences spindle position to accomplish an asymmetric division, presenting the current models of spindle orientation and anaphase spindle displacement. We focus on asymmetric cell division as a function of the actin and microtubule cytoskeletons, emphasizing the cell biology of polarity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.19.111301.113823
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  • 8
    Electronic Resource
    Electronic Resource
    SIGNALING PATHWAYS IN INTESTINAL DEVELOPMENT AND CANCER (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 695-723 
    Details
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The study of the epithelium of the adult mammalian intestine touches upon many modern aspects of biology. The epithelium is in a constant dialogue with the underlying mesenchyme to control stem cell activity, proliferation in transit-amplifying compartments, lineage commitment, terminal differentiation and, ultimately, cell death. There are spatially distinct compartments dedicated to each of these events. The Wnt, TGF-beta, BMP, Notch, and Par polarity pathways are the major players in homeostatic control of the adult epithelium. Several hereditary cancer syndromes deregulate these same signaling cascades through mutational (in)activation. Moreover, these mutations often also occur in sporadic tumors. Thus symmetry exists between the roles that these signaling pathways play in physiology and in cancer of the intestine. This is particularly evident for the Wnt/APC pathway, for which the mammalian intestine has become one of the most-studied paradigms. Here, we integrate recent knowledge of the molecular inner workings of the prototype signaling cascades with their specific roles in intestinal epithelial homeostasis and in neoplastic transformation of the epithelium.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.20.010403.092805
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  • 9
    Electronic Resource
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    PLASMODIUM SPOROZOITE MOLECULAR CELL BIOLOGY (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 29-59 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Plasmodium sporozoites display complex phenotypes including gliding motility and invasion of and transmigration through cells in the mosquito vector and the vertebrate host. Sporozoite studies have been difficult to perform because of technical concerns. Nevertheless, they have already provided insights into several aspects of sporozoite biology, shared in part with other apicomplexan invasive stages. Structure/function analysis of the thrombospondin-related anonymous protein paved the way to the understanding of the molecular mechanisms of apicomplexan gliding motility and host cell invasion. Functional studies of circumsporozoite protein revealed its role in Plasmodium sporozoite morphogenesis in addition to its well-known function in host cell invasion. Transcriptional surveys, which facilitate the investigation of gene expression programs that control sporozoite phenotypes, have revealed a high degree of previously unappreciated complexity and novel proteins that mediate sporozoite host cell infection.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.20.011603.150935
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  • 10
    Electronic Resource
    Electronic Resource
    THE BUDDING YEAST SPINDLE POLE BODY: Structure, Duplication, and Function (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 1-28 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Nucleation of microtubules by eukaryotic microtubule organizing centers (MTOCs) is required for a variety of functions, including chromosome segregation during mitosis and meiosis, cytokinesis, fertilization, cellular morphogenesis, cell motility, and intracellular trafficking. Analysis of MTOCs from different organisms shows that the structure of these organelles is widely varied even though they all share the function of microtubule nucleation. Despite their morphological diversity, many components and regulators of MTOCs, as well as principles in their assembly, seem to be conserved. This review focuses on one of the best-characterized MTOCs, the budding yeast spindle pole body (SPB). We review what is known about its structure, protein composition, duplication, regulation, and functions. In addition, we discuss how studies of the yeast SPB have aided investigation of other MTOCs, most notably the centrosome of animal cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.20.022003.114106
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  • 11
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    THE ROLE OF KNOX GENES IN PLANT DEVELOPMENT# (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 125-151 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: knox genes encode homeodomain-containing transcription factors that are required for meristem maintenance and proper patterning of organ initiation. In plants with simple leaves, knox genes are expressed exclusively in the meristem and stem, but in dissected leaves, they are also expressed in leaf primordia, suggesting that they may play a role in the diversity of leaf form. This hypothesis is supported by the intriguing phenotypes found in gain-of-function mutations where knox gene misexpression affects leaf and petal shape. Similar phenotypes are also found in recessive mutations of genes that function to negatively regulate knox genes. KNOX proteins function as heterodimers with other homeodomains in the TALE superclass. The gibberellin and lignin biosynthetic pathways are known to be negatively regulated by KNOX proteins, which results in indeterminate cell fates.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.20.031803.093824
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  • 12
    Electronic Resource
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    SPECIFICATION OF TEMPORAL IDENTITY IN THE DEVELOPING NERVOUS SYSTEM (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 619-647 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The nervous system of higher organisms exhibits extraordinary cellular diversity owing to complex spatial and temporal patterning mechanisms. The role of spatial patterning in generating neuronal diversity is well known; here we discuss how neural progenitors change over time to contribute to cell diversity within the central nervous system (CNS). We focus on five model systems: the vertebrate retina, cortex, hindbrain, spinal cord, and Drosophila neuroblasts. For each, we address the following questions: Do multipotent progenitors generate different neuronal cell types in an invariant order? Do changes in progenitor-intrinsic factors or progenitor-extrinsic signals regulate temporal identity (i.e., the sequence of neuronal cell types produced)? What is the mechanism that regulates temporal identity transitions; i.e., what triggers the switch from one temporal identity to the next? By applying the same criteria to analyze each model system, we try to highlight common themes, point out unique attributes of each system, and identify directions for future research.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.19.111301.115142
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  • 13
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    THE ADENOMATOUS POLYPOSIS COLI PROTEIN: The Achilles Heel of the Gut Epithelium (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 337-366 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The Adenomatous Polyposis coli (APC) gene is mutated or lost in most colon cancers, and the APC protein has emerged as a multifunctional protein that is not only involved in the Wnt-regulated degradation of -catenin, but also regulates cytoskeletal proteins and thus plays a role in cell migration, cell adhesion, and mitosis. The gut epithelium is uniquely dependent on an intricate balance between a number of fundamental cellular processes including migration, differentiation, adhesion, apoptosis, and mitosis. In this review, I discuss the molecular mechanisms that govern the various functions of APC and their relationship to the role of APC in colon cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.20.012103.094541
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  • 14
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    G PROTEIN CONTROL OF MICROTUBULE ASSEMBLY (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 867-894 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Microtubules are dynamic polymers required for many aspects of eukaryotic cell function. The interphase microtubule network is essential for intracellular transport, organization, and cell polarization, whereas the mitotic spindle is required for chromosome segregation and cell division. Studies in different areas such as cell migration, mitosis, and asymmetric cell division have shown that Ran, Rho, and heterotrimeric G proteins regulate many aspects of microtubule functions. This review surveys how G protein-signaling coordinates microtubule polymerization and organization with specific cellular activities.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.20.012103.094648
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  • 15
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    CELLULAR LENGTH CONTROL SYSTEMS (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 677-693 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The problem of organelle size control can be addressed most simply by considering cellular structures that are linear, so that their size can be defined by a single parameter: length. We compare existing studies on several linear biological structures including prokaryotic flagella and flagellar hooks, eukaryotic flagella, sarcomere thin filaments, and microvilli. In some cases, existing evidence strongly supports the idea that length control involves a molecular ruler, in which the size of the overall structure is compared with the size of an individual molecule. In other cases, length control is likely to involve a steady-state balance of assembly and disassembly, in which one or the other rate is inherently length dependent. The lessons learned from size control in linear structures should be applicable to organelles with more complex three-dimensional structures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.20.012103.094437
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  • 16
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    NEW DEVELOPMENTS IN MITOCHONDRIAL ASSEMBLY (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 309-335 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The mitochondrion has developed an elaborate translocation system for the import of nuclear-coded proteins and the export of proteins coded on the mitochondrial genome. Precursor proteins contain targeting and sorting information to reach the mitochondrion, whereas the translocons recognize the information and direct the precursor to the correct compartment. The outer membrane contains the TOM (translocase of the outer membrane) complex for translocation and the SAM (sorting and assembly machinery) complex for assembly of outer membrane proteins with complex topologies. At the inner membrane, the TIM23 (translocase of the inner membrane) mediates the import of mitochondrial proteins with a typical N-terminal targeting sequence, and the TIM22 complex mediates the import of polytopic inner membrane proteins. Based on its prokaryotic origin, the inner membrane also contains several components that mediate the export and assembly of proteins from within the matrix. Together the translocation and assembly complexes coordinate assembly of the mitochondrion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.20.010403.105057
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  • 17
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    THE GENETICS AND MOLECULAR BIOLOGY OF THE SYNAPTONEMAL COMPLEX (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 525-558 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The synaptonemal complex (SC) is a protein lattice that resembles railroad tracks and connects paired homologous chromosomes in most meiotic systems. The two side rails of the SC, known as lateral elements (LEs), are connected by proteins known as transverse filaments. The LEs are derived from the axial elements of the chromosomes and play important roles in chromosome condensation, pairing, transverse filament assembly, and prohibiting double-strand breaks (DSBs) from entering into recombination pathways that involve sister chromatids. The proteins that make up the transverse filaments of the SC also play a much earlier role in committing a subset of DSBs into a recombination pathway, which results in the production of reciprocal meiotic crossovers. Sites of crossover commitment can be observed as locations where the SC initiates and as immunostaining foci for a set of proteins required for the processing of DSBs to mature crossovers. In most (but not all) organisms it is the establishment of sites marking such crossover-committed DSBs that facilitates completion of synapsis (full-length extension of the SC). The function of the mature full-length SC may involve both the completion of meiotic recombination at the DNA level and the exchange of the axial elements of the two chromatids involved in the crossover. However, the demonstration that the sites of crossover formation are designated prior to SC formation, and the finding that these sites display interference, argues against a role of the mature SC in mediating the process of interference. Finally, in at least some organisms, modifications of the SC alone are sufficient to ensure meiotic chromosome segregation in the complete absence of meiotic recombination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.19.111301.155141
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  • 18
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    CONNEXINS AND CELL SIGNALING IN DEVELOPMENT AND DISEASE1 (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 811-838 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Gap junctions contain hydrophilic membrane channels that allow direct communication between neighboring cells through the diffusion of ions, metabolites, and small cell signaling molecules. They are made up of a hexameric array of polypeptides encoded by the connexin multi-gene family. Cell-cell communication mediated by connexins is crucial to various cellular functions, including the regulation of cell growth, differentiation, and development. Mutations in connexin genes have been linked to a variety of human diseases, including cardiovascular anomalies, peripheral neuropathy, deafness, skin disorders, and cataracts. In addition to their coupling function, recent studies suggest that connexin proteins may also mediate signaling. This could involve interactions with other protein partners that may play a role not only in connexin assembly, trafficking, gating and turnover, but also in the coordinate regulation of cell-cell communication with cell adhesion and cell motility. The integration of these cell functions is likely to be important in the role of gap junctions in development and disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.19.111301.144309
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  • 19
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    ADAPTORS FOR CLATHRIN COATS: Structure and Function (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 153-191 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Clathrin-coated vesicles (CCVs) are responsible for the transport of proteins between various compartments of the secretory and endocytic systems. Clathrin forms a scaffold around these vesicles that is linked to membranes by clathrin adaptors. The adaptors simultaneously bind to clathrin and to transmembrane proteins and/or phospholipids and can also interact with each other and with other components of the CCV formation machinery. The result is a collection of proteins that can make multiple, moderate strength (M Kd) interactions and thereby establish the dynamic regulatable networks to drive vesicle genesis at the correct time and place in the cell. This review focuses on the structure of clathrin adaptors and how these structures provide functional information on the mechanism of CCV formation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.20.010403.104543
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  • 20
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    MECHANISMS OF POLARIZED GROWTH AND ORGANELLE SEGREGATION IN YEAST (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 559-591 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Cell polarity, as reflected by polarized growth and organelle segregation during cell division in yeast, appears to follow a simple hierarchy. On the basis of physical cues from previous cell cycles or stochastic processes, yeast cells select a site for bud emergence that also defines the axis of cell division. Once polarity is established, rho protein-based signal pathways set up a polarized cytoskeleton by activating localized formins to nucleate and assemble polarized actin cables. These serve as tracks for the transport of secretory vesicles, the segregation of the trans Golgi network, the vacuole, peroxisomes, endoplasmic reticulum, mRNAs for cell fate determination, and microtubules that orient the nucleus in preparation for mitosis, all by myosin-Vs encoded by the MYO2 and MYO4 genes. Most of the proteins participating in these processes in yeast are conserved throughout the kingdoms of life, so the emerging models are likely to be generally applicable. Indeed, several parallels to cellular organization in animals are evident.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.20.010403.103108
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  • 21
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    THE ENGULFMENT PROCESS OF PROGRAMMED CELL DEATH IN CAENORHABDITIS ELEGANS (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 193-221 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Programmed cell death involves the removal of cell corpses by other cells in a process termed engulfment. Genetic studies of the nematode Caenorhabditis elegans have led to a framework not only for the killing step of programmed cell death but also for the process of cell-corpse engulfment. This work has defined two signal transduction pathways that act redundantly to control engulfment. Signals expressed by dying cells probably regulate these C. elegans pathways. Components of the cell-corpse recognition system of one of the C. elegans pathways include the CED-7 ABC transporter, which likely presents a death ligand on the surface of the dying cell; the CED-1 transmembrane receptor, which recognizes this signal; and the CED-6 adaptor protein, which may transduce a signal from CED-1. The second C. elegans pathway acts in parallel and involves a novel Rac GTPase signaling pathway, with the components CED-2 CrkII, CED-5 DOCK180, CED-12 ELMO, and CED-10 Rac. The cell-corpse recognition system that activates this pathway remains to be characterized. In C. elegans, and possibly in mammals, the process of cell-corpse engulfment promotes the death process itself. The known mechanisms for cell-corpse engulfment leave much to be discovered concerning this fundamental aspect of metazoan biology.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.20.022003.114619
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    CELL BIOLOGY OF MYCOBACTERIUM TUBERCULOSIS PHAGOSOME (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 367-394 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Phagocytosis and phagolysosome biogenesis represent fundamental biological processes essential for proper tissue homeostasis, development, elimination of invading microorganisms, and antigen processing and presentation. Phagosome formation triggers a preprogramed pathway of maturation into the phagolysosome, a process controlled by Ca2+ and the regulators of organellar trafficking centered around the small GTP-binding proteins Rabs and their downstream effectors, including lipid kinases, organellar tethering molecules, and membrane fusion apparatus. Mycobacterium tuberculosis is a potent human pathogen parasitizing macrophages. It interferes with the Rab-controlled membrane trafficking and arrests the maturing phagosome at a stage where no harm can be done to the pathogen while the delivery of nutrients and membrane to the vacuole harboring the microorganism continues. This process, referred to as the M. tuberculosis phagosome maturation arrest or inhibition of phagosome-lysosome fusion, is critical for M. tuberculosis persistence in human populations. It also provides a general model system for dissecting the phagolysosome biogenesis pathways. Here we review the fundamental trafficking processes targeted by M. tuberculosis and the mycobacterial products that interfere with phagosomal maturation.
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    CHEMOATTRACTANT SIGNALING IN DICTYOSTELIUM DISCOIDEUM (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 223-253 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Dictyostelium is an accessible organism for studies of signaling via chemoattractant receptors. Chemoattractant-mediated signaling events and components are reviewed and presented as a series of connected modules, including excitation, inhibition, G protein-independent responses, early gene expression, inositol lipids, PH domain-containing proteins, cyclic AMP signaling, polarization acquisition, actin polymerization, and cortical myosin. The network incorporates information from biochemical, genetic, and cell biological experiments carried out on living cells. The modules and connections represent current understanding, and future information is expected to modify and build upon this structure.
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    MEMBRANE DOMAINS (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 839-866 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Considerable evidence shows that lateral inhomogeneities in lipid composition and physical properties exist in biological membranes. These membrane lipid domains are proposed to play important roles in processes such as signal transduction and membrane traffic. However, there is not at present an adequate description of the nature of these lipid domains in terms of their size, abundance, composition, or dynamics. We discuss the current analyses of the properties and function of membrane domains in cells and compare their properties with chemically simpler model membrane systems that can be understood in greater detail.
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    URL: http://dx.doi.org/10.1146/annurev.cellbio.20.010403.095451
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    DYNACTIN (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 759-779 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Dynactin is a multisubunit protein complex that is required for most, if not all, types of cytoplasmic dynein activity in eukaryotes. Dynactin binds dynein directly and allows the motor to traverse the microtubule lattice over long distances. A single dynactin subunit, p150Glued, is sufficient for both activities, yet dynactin contains several other subunits that are organized into an elaborate structure. It is currently believed that the bulk of the dynactin structure participates in interactions with a wide range of cellular structures, many of which are cargoes of the dynein motor. Genetic studies verify the importance of all elements of dynactin structure to its function. Although dynein can bind some membranous cargoes independently of dynactin, establishment of a fully functional dynein-cargo link appears to depend on dynactin. In this review, I summarize what is presently known about dynactin structure, the cellular structures with which it associates, and the intermolecular interactions that underlie and regulate binding. Although the molecular details of dynactin's interactions with membranous organelles and other molecules are complex, the framework provided here is intended to distill what is presently known and to be of use to dynactin specialists and beginners alike.
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    THE WNT SIGNALING PATHWAY IN DEVELOPMENT AND DISEASE (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 781-810 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Tight control of cell-cell communication is essential for the generation of a normally patterned embryo. A critical mediator of key cell-cell signaling events during embryogenesis is the highly conserved Wnt family of secreted proteins. Recent biochemical and genetic analyses have greatly enriched our understanding of how Wnts signal, and the list of canonical Wnt signaling components has exploded. The data reveal that multiple extracellular, cytoplasmic, and nuclear regulators intricately modulate Wnt signaling levels. In addition, receptor-ligand specificity and feedback loops help to determine Wnt signaling outputs. Wnts are required for adult tissue maintenance, and perturbations in Wnt signaling promote both human degenerative diseases and cancer. The next few years are likely to see novel therapeutic reagents aimed at controlling Wnt signaling in order to alleviate these conditions.
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    RNA TRANSLATION IN AXONS (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 505-523 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The cell body has classically been considered the exclusive source of axonal proteins. However, significant evidence has accumulated recently to support the view that protein synthesis can occur in axons themselves, remote from the cell body. Indeed, local translation in axons may be integral to aspects of synaptogenesis, long-term facilitation, and memory storage in invertebrate axons, and for growth cone navigation in response to environmental stimuli in developing vertebrate axons. Here we review the evidence supporting mRNA translation in axons and discuss the potential roles that local protein synthesis may play during development and subsequent neuronal function. We advance the view that local translation provides a rapid supply of nascent proteins in restricted axonal compartments that can potentially underlie long-term responses to transient stimuli.
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    REGULATION OF MUSCLE MASS BY MYOSTATIN (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 61-86 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Myostatin is a secreted protein that acts as a negative regulator of skeletal muscle mass. During embryogenesis, myostatin is expressed by cells in the myotome and in developing skeletal muscle and acts to regulate the final number of muscle fibers that are formed. During adult life, myostatin protein is produced by skeletal muscle, circulates in the blood, and acts to limit muscle fiber growth. The existence of circulating tissue-specific growth inhibitors of this type was hypothesized over 40 years ago to explain how sizes of individual tissues are controlled. Skeletal muscle appears to be the first example of a tissue whose size is controlled by this type of regulatory mechanism, and myostatin appears to be the first example of the long-sought chalone.
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    LAMININ FUNCTIONS IN TISSUE MORPHOGENESIS (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 255-284 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Significant advances have been made in the application of genetics to probe the functions of basement membrane laminins. These studies have shown that different laminin subunits profoundly affect tissue morphogenesis, starting around the time of embryonic implantation and extending through organogenesis and into the postnatal period. Collectively they have revealed common functions that include the induction and maintenance of cell polarity, the establishment of barriers between tissue compartments, the organization of cells into tissues, and the protection of adherent cells from detachment-induced cell death, anoikis. Interpreted in light of what is known about laminin structure and self-assembly and binding activities, these advances have begun to provide insights into mechanisms of action. In this review we focus on the contributions of the laminins in invertebrate and vertebrate tissue morphogenesis.
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    RETROVIRUS BUDDING (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 395-425 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Human immunodeficiency virus (HIV) and other retroviruses acquire their envelopes and spread infection by budding through the limiting membranes of producer cells. To facilitate budding, retroviruses usurp a cellular pathway that is normally used to create vesicles that bud into late endosomal compartments called multivesicular bodies (MVB). Research on yeast and human MVB biogenesis has led to the identification of 25 human proteins that are required for vesicle formation and for HIV-1 budding, and has produced a working model for sequential recruitment of these proteins during MVB vesicle formation. Retroviruses can redirect this machinery to the plasma membrane and leave the cell in a single step or, alternatively, can bud directly into MVB compartments and then exit cells via the exosome pathway. Remarkably, virus release from both the plasma membrane and MVB compartments can occur directionally into specialized sites of cell-to-cell contact called virological synapses. Thus retroviruses have evolved elaborate mechanisms for escaping the cell and maximizing their chances of infecting a new host.
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    MYOSIN VI: Cellular Functions and Motor Properties (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 20 (2004), S. 649-676 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Myosin motor proteins use the energy derived from ATP hydrolysis to move cargo along actin tracks. Myosin VI, unlike almost all other myosins, moves toward the minus end of actin filaments and functions in a variety of intracellular processes such as vesicular membrane traffic, cell migration, and mitosis. These diverse roles of myosin VI are mediated by interaction with a number of different binding partners present in multi-protein complexes. Myosin VI can work in vitro as a processive dimeric motor and as a nonprocessive monomeric motor, each with a large working stroke. The possibility that both monomeric and dimeric forms of myosin VI operate in the cell may represent an important regulatory mechanism for controlling the multiple steps in transport pathways where nonprocessive and processive motors are required.
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    CD1: Antigen Presentation and T Cell Function (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 22 (2004), S. 817-890 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: This review summarizes the major features of CD1 genes and proteins, the patterns of intracellular trafficking of CD1 molecules, and how they sample different intracellular compartments for self- and foreign lipids. We describe how lipid antigens bind to CD1 molecules with their alkyl chains buried in hydrophobic pockets and expose their polar lipid headgroup whose fine structure is recognized by the TCR of CD1-restricted T cells. CD1-restricted T cells carry out effector, helper, and adjuvant-like functions and interact with other cell types including macrophages, dendritic cells, NK cells, T cells, and B cells, thereby contributing to both innate and adaptive immune responses. Insights gained from mice and humans now delineate the extensive range of diseases in which CD1-restricted T cells play important roles and reveal differences in the role of CD1a, CD1b, and CD1c in contrast to CD1d. Invariant TCRalpha chains, self-lipid reactivity, and rapid effector responses empower a subset of CD1d-restricted T cells (NKT cells) to have unique effector functions without counterpart among MHC-restricted T cells. This review describes the function of CD1-restricted T cells in antimicrobial responses, antitumor immunity, and in regulating the balance between tolerance and autoimmunity.
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    The Three Es of Cancer Immunoediting (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 22 (2004), S. 329-360 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: After a century of controversy, the notion that the immune system regulates cancer development is experiencing a new resurgence. An overwhelming amount of data from animal models-together with compelling data from human patients-indicate that a functional cancer immunosurveillance process indeed exists that acts as an extrinsic tumor suppressor. However, it has also become clear that the immune system can facilitate tumor progression, at least in part, by sculpting the immunogenic phenotype of tumors as they develop. The recognition that immunity plays a dual role in the complex interactions between tumors and the host prompted a refinement of the cancer immunosurveillance hypothesis into one termed "cancer immunoediting." In this review, we summarize the history of the cancer immunosurveillance controversy and discuss its resolution and evolution into the three Es of cancer immunoediting-elimination, equilibrium, and escape.
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    CD40/CD154 Interactions at the Interface of Tolerance and Immunity (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 22 (2004), S. 307-328 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Development of the acquired immune response is dependent on the signaling of CD40 by its ligand, CD154. These molecules govern both the magnitude and quality of humoral- and cell-mediated immunity. A litany of studies have conclusively documented that blockade of this ligand-receptor pair can prevent, and also intervene in, the progression of antibody- and cell-mediated autoimmune diseases, and can instill long-lived allogeneic and xenogeneic graft tolerance. Many effector mechanisms of inflammation are abolished as a result of CD154 blockade, but we are now beginning to understand that CD154 blockade may, in some instances, engender long-lived, antigen-specific tolerance. In the context of transplantation tolerance, we present a hypothesis that alphaCD154 blockade is most effective at inducing long-lived allospecific tolerance if anergy and regulation can be elicited prior to the onslaught of inflammation that is induced by grafting (preemptive tolerance). This facet of alphaCD154-induced tolerance appears to co-opt the normal processes of peripheral tolerance induced by immature DCs and can be exploited to induce long-lived antigen-specific tolerance. The underlying science and the prospects for inducing long-lived antigen-specific tolerance in a model of allograft tolerance through CD154 blockade are presented and discussed.
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    Ligands for L-Selectin: Homing, Inflammation, and Beyond (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 22 (2004), S. 129-156 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Understanding the molecular basis of lymphocyte homing to lymphoid organs was originally a problem of concern only to immunologists. With the discovery of l-selectin and its ligands, interested scientists have expanded to include glycobiologists, immunopathologists, cancer biologists, and developmental biologists. Going beyond its first discovered role in homing to lymph nodes, the l-selectin system is implicated in such diverse processes as inflammatory leukocyte trafficking in both acute and chronic settings, hematogenous metastasis of carcinoma cells, effector mechanisms for inflammatory demyelination of axons, and implantation of the early mammalian embryo. This review focuses on the ligands for l-selectin that are found on vascular endothelium, leukocytes, carcinoma cells, and at various extravascular sites. The discovery of selectins and their ligands has validated the long-predicted hypothesis that carbohydrate-directed cell adhesion is relevant in eukaryotic systems. Emphasis will be given to the carbohydrate and sulfation modifications of the ligands, which enable recognition by l-selectin. The rapid "homing" of labeled cells into the lymph nodes presumably had its basis in the special affinity of small lymphocytes for the endothelium of the postcapillary venules. Gowans & Knight (1)
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    Interleukin-10 and Related Cytokines and Receptors (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 22 (2004), S. 929-979 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The Class 2 alpha-helical cytokines consist of interleukin-10 (IL-10), IL-19, IL-20, IL-22, IL-24 (Mda-7), and IL-26, interferons (IFN-alpha, -beta, -e, -kappa, -omega, -delta, -tau, and -gamma) and interferon-like molecules (limitin, IL-28A, IL-28B, and IL-29). The interaction of these cytokines with their specific receptor molecules initiates a broad and varied array of signals that induce cellular antiviral states, modulate inflammatory responses, inhibit or stimulate cell growth, produce or inhibit apoptosis, and affect many immune mechanisms. The information derived from crystal structures and molecular evolution has led to progress in the analysis of the molecular mechanisms initiating their biological activities. These cytokines have significant roles in a variety of pathophysiological processes as well as in regulation of the immune system. Further investigation of these critical intercellular signaling molecules will provide important information to enable these proteins to be used more extensively in therapy for a variety of diseases.
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    Drosophila: The Genetics of Innate Immune Recognition and Response (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 22 (2004), S. 457-483 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Because of the evolutionary conservation of innate mechanisms of host defense, Drosophila has emerged as an ideal animal in which to study the genetic control of immune recognition and responses. The discovery that the Toll pathway is required for defense against fungal infection in Drosophila was pivotal in studies of both mammalian and Drosophila immunity. Subsequent genetic screens in Drosophila to isolate additional mutants unable to induce humoral responses to infection have identified and ordered the function of components of two signaling cascades, the Toll and Imd pathways, that activate responses to infection. Drosophila blood cells also contribute to host defense through phagocytosis and signaling, and may carry out a form of self-nonself recognition that is independent of microbial pattern recognition. Recent work suggests that Drosophila will be a useful model for dissecting virulence mechanisms of several medically important pathogens.
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    Physiological Control of Immune Response and Inflammatory Tissue Damage by Hypoxia-Inducible Factors and Adenosine A2A Receptors* (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 22 (2004), S. 657-682 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Immune cell-mediated destruction of pathogens may result in excessive collateral damage to normal tissues, and the failure to control activated immune cells may cause immunopathologies. The search for physiological mechanisms that downregulate activated immune cells has revealed a critical role for extracellular adenosine and for immunosuppressive A2A adenosine receptors in protecting tissue from inflammatory damage. Tissue damage-associated deep hypoxia, hypoxia-inducible factors, and hypoxia-induced accumulation of adenosine may represent one of the most fundamental and immediate tissue-protecting mechanisms, with adenosine A2A receptors triggering "OFF" signals in activated immune cells. In these regulatory mechanisms, oxygen deprivation and extracellular adenosine accumulation serve as "reporters," while A2A adenosine receptors serve as "sensors" of excessive tissue damage. The A2A receptor-triggered generation of intracellular cAMP then inhibits activated immune cells in a delayed negative feedback manner to prevent additional tissue damage. Targeting A2A adenosine receptors may have important clinical applications.
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    Autoimmune and Inflammatory Mechanisms in Atherosclerosis (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 22 (2004), S. 361-403 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The present review focuses on the concept that cellular and humoral immunity to the phylogenetically highly conserved antigen heat shock protein 60 (HSP60) is the initiating mechanism in the earliest stages of atherosclerosis. Subjecting arterial endothelial cells to classical atherosclerosis risk factors leads to the expression of HSP60 that then may serve as a target for pre-existent cross-reactive antimicrobial HSP60 immunity or bona fide autoimmune reactions induced by biochemically altered autologous HSP60. Endothelial cells can also bind microbial or autologous HSP60 via Toll-like receptors, providing another possibility for targetting adaptive or innate immunological effector mechanisms.
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    Field Physiology: Physiological Insights from Animals in Nature (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 66 (2004), S. 209-238 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Whereas comparative physiology documents the range of physiological variation across a range of organisms, field physiology provides insight into the actual mechanisms an organism employs to maintain homeostasis in its everyday life. This requires an understanding of an organism's natural history and is prerequisite to developing hypotheses about physiological mechanisms. This review focuses on a few areas of field physiology that exemplify how the underlying physiology could not have been understood without appropriate field measurements. The examples we have chosen highlight the methods and inference afforded by an application of this physiological analysis to organismal function in nature, often in extreme environments. The specific areas examined are diving physiology, the thermal physiology of large endothermic fishes, reproductive physiology of air breathing vertebrates, and endocrine physiology of reproductive homeostasis. These areas form a bridge from physiological ecology to evolutionary ecology. All our examples revolve around the central issue of physiological limits as they apply to organismal homeostasis. We view this theme as the cornerstone of physiological analysis and supply a number of paradigms on homeostasis that have been tested in the context of field physiology.
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    Biochemical Indicators of Stress and Metabolism: Applications for Marine Ecological Studies (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 66 (2004), S. 183-207 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Studies investigating the effects of temperature, food availability, or other physical factors on the physiology of marine animals have led to the development of biochemical indicators of growth rate, metabolic condition, and physiological stress. Measurements of metabolic enzyme activity and RNA/DNA have been especially valuable as indicators of condition in studies of marine invertebrates and fishes, groups for which accurate determination of field metabolic rates is difficult. Properly calibrated and applied, biochemical indicators have been successfully used in studies of rocky intertidal ecology, where two decades of experimentation have generated rigorous, testable models for determining the relative influences of biotic and abiotic factors on species distribution, abundance, and interaction. Biochemical indicators of condition and metabolic activity (metabolic enzymes, RNA/DNA) have been used to test nutrient-productivity models by demonstrating tight linkages between nearshore oceanographic processes (such as upwelling) and benthic rocky intertidal ecosystems. Indices of condition and heat stress (heat shock proteins, or Hsps) have begun to be used to test environmental stress models by comparing condition, activity, and Hsp expression of key rocky intertidal predator and prey species. Using biochemical indicators of condition and stress in natural systems holds great promise for understanding mechanisms by which organisms respond to rapid environmental change.
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    Developmental Regulation of Lung Liquid Transport (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 66 (2004), S. 77-101 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: The developing distal lung epithelium displays an evolving liquid transport phenotype, reflecting a changing and dynamic balance between Cl- ion secretion and Na+ ion absorption, which in turn reflects changing functional requirements. Thus in the fetus, Cl--driven liquid secretion predominates throughout gestation and generates a distending pressure to stretch the lung and stimulate growth. Increasing Na+ absorptive capacity develops toward term, anticipating the switch to an absorptive phenotype at birth and beyond. There is some empirical evidence of ligand-gated regulation of Cl- transport and of regulation via changes in the driving force for Cl- secretion. Epinephrine, O2, glucocorticoid, and thyroid hormones interact to stimulate Na+ absorption by increasing Na+ pump activity and apical Na+ conductance (GNa+) to bring about the switch from net secretion to net absorption as lung liquid is cleared from the lung at birth. Postnatally, the lung lumen contains a small Cl--based liquid secretion that generates a surface liquid layer, but the lung retains a large absorptive capacity to prevent alveolar flooding and clear edema fluid. This review explores the mechanisms underlying the functional development of the lung epithelium and draws upon evidence from classic integrative physiological studies combined with molecular physiology approaches.
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    URL: http://dx.doi.org/10.1146/annurev.physiol.66.071702.145229
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    Estrogens in the Nervous System: Mechanisms and Nonreproductive Functions (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 66 (2004), S. 291-313 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: The past decade has witnessed a growing interest in estrogens and their activity in the central nervous system, which was originally believed to be restricted to the control of reproduction. It is now well accepted that estrogens modulate the activity of all types of neural cells through a multiplicity of mechanisms. Estrogens, by binding to two cognate receptors ERalpha and ERbeta, may interact with selected promoters to initiate the synthesis of target proteins. Alternatively, the hormone receptor complex may interfere with intracellular signaling at both cytoplasmic and nuclear levels. The generation of cellular and animal models, combined with clinical and epidemiological studies, has allowed us to appreciate the neurotrophic and neuroprotective effects of estrogens. These findings are of major interest because estradiol might become an important therapeutic agent to maintain neural functions during aging and in selected neural diseases.
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    URL: http://dx.doi.org/10.1146/annurev.physiol.66.032802.154945
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    The Role of Corepressors in Transcriptional Regulation by Nuclear Hormone Receptors (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 66 (2004), S. 315-360 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Nuclear receptors (also known as nuclear hormone receptors) are hormone-regulated transcription factors that control many important physiological and developmental processes in animals and humans. Defects in receptor function result in disease. The diverse biological roles of these receptors reflect their surprisingly versatile transcriptional properties, with many receptors possessing the ability to both repress and activate target gene expression. These bipolar transcriptional properties are mediated through the interactions of the receptors with two distinct classes of auxiliary proteins: corepressors and coactivators. This review focuses on how corepressors work together with nuclear receptors to repress gene transcription in the normal organism and on the aberrations in this process that lead to neoplasia and endocrine disorders. The actions of coactivators and the contributions of the same corepressors to the functions of nonreceptor transcription factors are also touched on.
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    URL: http://dx.doi.org/10.1146/annurev.physiol.66.032802.155556
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    Myosin-1c, the Hair Cell's Adaptation Motor (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 66 (2004), S. 521-545 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Given their prominent actin-rich subcellular specializations, it is no surprise that mechanosensitive hair cells of the inner ear exploit myosin molecules-the only known actin-dependent molecular motors-to carry out exotic but essential tasks. Recent experiments have confirmed that an unconventional myosin isozyme, myosin-1c, is a component of the hair cell's adaptation-motor complex. This complex carries out slow adaptation, provides tension to sensitize transduction channels, and may participate in assembly of the transduction apparatus. This review focuses on the detailed operation of the adaptation motor and the functional consequences of the incorporation of this specific myosin isozyme into the motor complex.
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    URL: http://dx.doi.org/10.1146/annurev.physiol.66.032102.112842
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    Localization of Voltage-Gated Ion Channels IN Mammalian Brain (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 66 (2004), S. 477-519 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: The intrinsic electrical properties of neurons are shaped in large part by the action of voltage-gated ion channels. Molecular cloning studies have revealed a large family of ion channel genes, many of which are expressed in mammalian brain. Much recent effort has focused on determining the contribution of the protein products of these genes to neuronal function. This requires knowledge of the abundance and distribution of the constituent subunits of the channels in specific mammalian central neurons. Here we review progress made in recent studies aimed at localizing specific ion channel subunits using in situ hybridization and immunohistochemistry. We then discuss the implications of these results in terms of neuronal physiology and neuronal mechanisms underlying the observed patterns of expression.
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    URL: http://dx.doi.org/10.1146/annurev.physiol.66.032102.113328
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    Bacteriorhodopsin (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 66 (2004), S. 665-688 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Fourier transform infrared and Raman spectroscopy, solid-state NMR, and X-ray crystallography have contributed detailed information about the structural changes in the proton transport cycle of the light-driven pump, bacteriorhodopsin. The results over the past few years add up to a step-by-step description of the configurational changes of the photoisomerized retinal, how these changes result in internal proton transfers and the release of a proton to the extracellular surface and uptake on the other side, as well as the conservation and transformation of excess free energy during the cycle.
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    URL: http://dx.doi.org/10.1146/annurev.physiol.66.032102.150049
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    Interpreting the BOLD Signal (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 66 (2004), S. 735-769 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: The development of functional magnetic resonance imaging (fMRI) has brought together a broad community of scientists interested in measuring the neural basis of the human mind. Because fMRI signals are an indirect measure of neural activity, interpreting these signals to make deductions about the nervous system requires some understanding of the signaling mechanisms. We describe our current understanding of the causal relationships between neural activity and the blood-oxygen-level-dependent (BOLD) signal, and we review how these analyses have challenged some basic assumptions that have guided neuroscience. We conclude with a discussion of how to use the BOLD signal to make inferences about the neural signal.
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    URL: http://dx.doi.org/10.1146/annurev.physiol.66.082602.092845
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    Genetically Engineered Mouse Models for Lung Cancer (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 66 (2004), S. 647-663 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: The lung is a complex organ consisting of numerous cell types that function to ensure sufficient gas exchange to oxygenate the blood. In order to accomplish this function, the lung must be exposed to the external environment and at the same time maintain a homeostatic balance between its function in gas exchange and the maintenance of inflammatory balance. During the past two decades, as molecular methodologies have evolved with the sequencing of entire genomes, the use of in vivo models to elucidate the molecular mechanisms involved in pulmonary physiology and disease have increased. The mouse has emerged as a potent model to investigate pulmonary physiology due to the explosion in molecular methods that now allow for the developmental and tissue-specific regulation of gene transcription. Initial efforts to manipulate gene expression in the mouse genome resulted in the generation of transgenic mice characterized by the constitutive expression of a specific gene and knockout mice characterized by the ablation of a specific gene. The utility of these original mouse models was limited, in many cases, by phenotypes resulting in embryonic or neonatal lethality that prevented analysis of the impact of the genetic manipulation on pulmonary biology. Second-generation transgenic mouse models employ multiple strategies that can either activate or silence gene expression thereby providing extensive temporal and spatial control of the experimental parameters of gene expression. These highly regulated mouse models are intended to serve as a foundation for further investigation of the molecular basis of human disease such as tumorigenesis. This review describes the principles, progress, and application of systems that are currently employed in the conditional regulation of gene expression in the investigation of lung cancer.
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    URL: http://dx.doi.org/10.1146/annurev.physiol.66.032102.134301
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    The Cytochrome bc1 Complex: Function in the Context of Structure (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 66 (2004), S. 689-733 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: The bc1 complexes are intrinsic membrane proteins that catalyze the oxidation of ubihydroquinone and the reduction of cytochrome c in mitochondrial respiratory chains and bacterial photosynthetic and respiratory chains. The bc1 complex operates through a Q-cycle mechanism that couples electron transfer to generation of the proton gradient that drives ATP synthesis. Genetic defects leading to mutations in proteins of the respiratory chain, including the subunits of the bc1 complex, result in mitochondrial myopathies, many of which are a direct result of dysfunction at catalytic sites. Some myopathies, especially those in the cytochrome b subunit, exacerbate free-radical damage by enhancing superoxide production at the ubihydroquinone oxidation site. This bypass reaction appears to be an unavoidable feature of the reaction mechanism. Cellular aging is largely attributable to damage to DNA and proteins from the reactive oxygen species arising from superoxide and is a major contributing factor in many diseases of old age. An understanding of the mechanism of the bc1 complex is therefore central to our understanding of the aging process. In addition, a wide range of inhibitors that mimic the quinone substrates are finding important applications in clinical therapy and agronomy. Recent structural studies have shown how many of these inhibitors bind, and have provided important clues to the mechanism of action and the basis of resistance through mutation. This paper reviews recent advances in our understanding of the mechanism of the bc1 complex and their relation to these physiologically important issues in the context of the structural information available.
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    URL: http://dx.doi.org/10.1146/annurev.physiol.66.032102.150251
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    Live Optical Imaging of Nervous System Development (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 66 (2004), S. 771-798 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Although development of the nervous system is inherently a process of dynamic change, until recently it has generally been investigated by inference from static images. However, advances in live optical imaging are now allowing direct observation of growth, synapse formation, and even incipient function in the developing nervous system, at length scales from molecules to cortical regions, and over timescales from milliseconds to months. In this review, we provide technical background and present examples of how these new methods, including confocal and two-photon microscopy, GFP-based markers, and functional indicators, are being applied to provide fresh insight into long-standing questions of neural development.
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    URL: http://dx.doi.org/10.1146/annurev.physiol.66.082602.095217
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    Control of the Size of the Human Muscle Mass (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 66 (2004), S. 799-828 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: This review is divided into two parts, the first dealing with the cell and molecular biology of muscle in terms of growth and wasting and the second being an account of current knowledge of physiological mechanisms involved in the alteration of size of the human muscle mass. Wherever possible, attempts have been made to interrelate the information in each part and to provide the most likely explanation for phenomena that are currently only partially understood. The review should be of interest to cell and molecular biologists who know little of human muscle physiology and to physicians, physiotherapists, and kinesiologists who may be familiar with the gross behavior of human muscle but wish to understand more about the underlying mechanisms of change.
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    URL: http://dx.doi.org/10.1146/annurev.physiol.66.052102.134444
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    DESENSITIZATION OF G PROTEIN-COUPLED RECEPTORS AND NEURONAL FUNCTIONS (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 27 (2004), S. 107-144 
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    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: G protein-coupled receptors (GPCRs) have proven to be the most highly favorable class of drug targets in modern pharmacology. Over 90% of nonsensory GPCRs are expressed in the brain, where they play important roles in numerous neuronal functions. GPCRs can be desensitized following activation by agonists by becoming phosphorylated by members of the family of G protein-coupled receptor kinases (GRKs). Phosphorylated receptors are then bound by arrestins, which prevent further stimulation of G proteins and downstream signaling pathways. Discussed in this review are recent progress in understanding basics of GPCR desensitization, novel functional roles, patterns of brain expression, and receptor specificity of GRKs and betaarrestins in major brain functions. In particular, screening of genetically modified mice lacking individual GRKs or betaarrestins for alterations in behavioral and biochemical responses to cocaine and morphine has revealed a functional specificity in dopamine and mu-opioid receptor regulation of locomotion and analgesia. An important and specific role of GRKs and betaarrestins in regulating physiological responsiveness to psychostimulants and morphine suggests potential involvement of these molecules in certain brain disorders, such as addiction, Parkinson's disease, mood disorders, and schizophrenia. Furthermore, the utility of a pharmacological strategy aimed at targeting this GPCR desensitization machinery to regulate brain functions can be envisaged.
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    URL: http://dx.doi.org/10.1146/annurev.neuro.27.070203.144206
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    ATTENTIONAL MODULATION OF VISUAL PROCESSING (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 27 (2004), S. 611-647 
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    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Single-unit recording studies in the macaque have carefully documented the modulatory effects of attention on the response properties of visual cortical neurons. Attention produces qualitatively different effects on firing rate, depending on whether a stimulus appears alone or accompanied by distracters. Studies of contrast gain control in anesthetized mammals have found parallel patterns of results when the luminance contrast of a stimulus increases. This finding suggests that attention has co-opted the circuits that mediate contrast gain control and that it operates by increasing the effective contrast of the attended stimulus. Consistent with this idea, microstimulation of the frontal eye fields, one of several areas that control the allocation of spatial attention, induces spatially local increases in sensitivity both at the behavioral level and among neurons in area V4, where endogenously generated attention increases contrast sensitivity. Studies in the slice have begun to explain how modulatory signals might cause such increases in sensitivity.
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    URL: http://dx.doi.org/10.1146/annurev.neuro.26.041002.131039
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    THE HUMAN VISUAL CORTEX (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 27 (2004), S. 649-677 
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    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The discovery and analysis of cortical visual areas is a major accomplishment of visual neuroscience. In the past decade the use of noninvasive functional imaging, particularly functional magnetic resonance imaging (fMRI), has dramatically increased our detailed knowledge of the functional organization of the human visual cortex and its relation to visual perception. The fMRI method offers a major advantage over other techniques applied in neuroscience by providing a large-scale neuroanatomical perspective that stems from its ability to image the entire brain essentially at once. This bird's eye view has the potential to reveal large-scale principles within the very complex plethora of visual areas. Thus, it could arrange the entire constellation of human visual areas in a unified functional organizational framework. Here we review recent findings and methods employed to uncover the functional properties of the human visual cortex focusing on two themes: functional specialization and hierarchical processing.
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    HOW THE BRAIN PROCESSES SOCIAL INFORMATION: Searching for the Social Brain* (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 27 (2004), S. 697-722 
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    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Because information about gender, kin, and social status are essential for reproduction and survival, it seems likely that specialized neural mechanisms have evolved to process social information. This review describes recent studies of four aspects of social information processing: (a) perception of social signals via the vomeronasal system, (b) formation of social memory via long-term filial imprinting and short-term recognition, (c) motivation for parental behavior and pair bonding, and (d) the neural consequences of social experience. Results from these studies and some recent functional imaging studies in human subjects begin to define the circuitry of a "social brain." Such neurodevelopmental disorders as autism and schizophrenia are characterized by abnormal social cognition and corresponding deficits in social behavior; thus social neuroscience offers an important opportunity for translational research with an impact on public health.
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    URL: http://dx.doi.org/10.1146/annurev.neuro.27.070203.144148
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    THE SYNAPTIC VESICLE CYCLE (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 27 (2004), S. 509-547 
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    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Neurotransmitter release is mediated by exocytosis of synaptic vesicles at the presynaptic active zone of nerve terminals. To support rapid and repeated rounds of release, synaptic vesicles undergo a trafficking cycle. The focal point of the vesicle cycle is Ca2+-triggered exocytosis that is followed by different routes of endocytosis and recycling. Recycling then leads to the docking and priming of the vesicles for another round of exo- and endocytosis. Recent studies have led to a better definition than previously available of how Ca2+ triggers exocytosis and how vesicles recycle. In particular, insight into how Munc18-1 collaborates with SNARE proteins in fusion, how the vesicular Ca2+ sensor synaptotagmin 1 triggers fast release, and how the vesicular Rab3 protein regulates release by binding to the active zone proteins RIM1alpha and RIM2alpha has advanced our understanding of neurotransmitter release. The present review attempts to relate these molecular data with physiological results in an emerging view of nerve terminals as macromolecular machines.
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    THE NEUROBIOLOGY OF THE ASCIDIAN TADPOLE LARVA: Recent Developments in an Ancient Chordate (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 27 (2004), S. 453-485 
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    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: With little more than 330 cells, two thirds within the sensory vesicle, the CNS of the tadpole larva of the ascidian Ciona intestinalis provides us with a chordate nervous system in miniature. Neurulation, neurogenesis and its genetic bases, as well as the gene expression territories of this tiny constituency of cells all follow a chordate plan, giving rise in some cases to frank structural homologies with the vertebrate brain. Recent advances are fueled by the release of the genome and EST expression databases and by the development of methods to transfect embryos by electroporation. Immediate prospects to test the function of neural genes are based on the isolation of mutants by classical genetics and insertional mutagenesis, as well as by the disruption of gene function by morpholino antisense oligo-nucleotides. Coupled with high-speed video analysis of larval swimming, optophysiological methods offer the prospect to analyze at single-cell level the function of a CNS built on a vertebrate plan.
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    ELECTRICAL SYNAPSES IN THE MAMMALIAN BRAIN (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 27 (2004), S. 393-418 
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    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Many neurons in the mammalian central nervous system communicate through electrical synapses, defined here as gap junction-mediated connections. Electrical synapses are reciprocal pathways for ionic current and small organic molecules. They are often strong enough to mediate close synchronization of subthreshold and spiking activity among clusters of neurons. The most thoroughly studied electrical synapses occur between excitatory projection neurons of the inferior olivary nucleus and between inhibitory interneurons of the neocortex, hippocampus, and thalamus. All these synapses require the gap junction protein connexin36 (Cx36) for robust electrical coupling. Cx36 appears to interconnect neurons exclusively, and it is expressed widely along the mammalian neuraxis, implying that there are undiscovered electrical synapses throughout the central nervous system. Some central neurons may be electrically coupled by other connexin types or by pannexins, a newly described family of gap junction proteins. Electrical synapses are a ubiquitous yet underappreciated feature of neural circuits in the mammalian brain.
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    CORTICAL NEURAL PROSTHETICS (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 27 (2004), S. 487-507 
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    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Control of prostheses using cortical signals is based on three elements: chronic microelectrode arrays, extraction algorithms, and prosthetic effectors. Arrays of microelectrodes are permanently implanted in cerebral cortex. These arrays must record populations of single- and multiunit activity indefinitely. Information containing position and velocity correlates of animate movement needs to be extracted continuously in real time from the recorded activity. Prosthetic arms, the current effectors used in this work, need to have the agility and configuration of natural arms. Demonstrations using closed-loop control show that subjects change their neural activity to improve performance with these devices. Adaptive-learning algorithms that capitalize on these improvements show that this technology has the capability of restoring much of the arm movement lost with immobilizing deficits.
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    CRITICAL PERIOD REGULATION (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 27 (2004), S. 549-579 
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    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Neuronal circuits are shaped by experience during critical periods of early postnatal life. The ability to control the timing, duration, and closure of these heightened levels of brain plasticity has recently become experimentally accessible, especially in the developing visual system. This review summarizes our current understanding of known critical periods across several systems and species. It delineates a number of emerging principles: functional competition between inputs, role for electrical activity, structural consolidation, regulation by experience (not simply age), special role for inhibition in the CNS, potent influence of attention and motivation, unique timing and duration, as well as use of distinct molecular mechanisms across brain regions and the potential for reactivation in adulthood. A deeper understanding of critical periods will open new avenues to "nurture the brain"-from international efforts to link brain science and education to improving recovery from injury and devising new strategies for therapy and lifelong learning.
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    CEREBELLUM-DEPENDENT LEARNING: The Role of Multiple Plasticity Mechanisms (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 27 (2004), S. 581-609 
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    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The cerebellum is an evolutionarily conserved structure critical for motor learning in vertebrates. The model that has influenced much of the work in the field for the past 30 years suggests that motor learning is mediated by a single plasticity mechanism in the cerebellum: long-term depression (LTD) of parallel fiber synapses onto Purkinje cells. However, recent studies of simple behaviors such as the vestibulo-ocular reflex (VOR) indicate that multiple plasticity mechanisms contribute to cerebellum-dependent learning. Multiple plasticity mechanisms may provide the flexibility required to store memories over different timescales, regulate the dynamics of movement, and allow bidirectional changes in movement amplitude. These plasticity mechanisms must act in combination with appropriate information-coding strategies to equip motor-learning systems with the ability to express learning in correct contexts. Studies of the patterns of generalization of motor learning in the VOR provide insight about the coding of information in neurons at sites of plasticity. These principles emerging from studies of the VOR are consistent with results concerning more complex behaviors and thus may reflect general principles of cerebellar function.
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    THE NOGO SIGNALING PATHWAY FOR REGENERATION BLOCK (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 27 (2004), S. 341-368 
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    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: A hostile environment and decreased regenerative capacity may contribute to the failure of axon regeneration in the adult central nervous system. Recent studies leading to the identification of several myelin-associated inhibitors and their signaling molecules provide opportunitities to assess the contribution of these inhibitory molecules in restricting axon regeneration. These findings may ultimately allow for the development of strategies to alleviate the inhibitory effects of such molecules in an effort to encourage axon regeneration after spinal cord and brain injury.
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    NEURONAL CIRCUITS OF THE NEOCORTEX (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 27 (2004), S. 419-451 
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    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: We explore the extent to which neocortical circuits generalize, i.e., to what extent can neocortical neurons and the circuits they form be considered as canonical? We find that, as has long been suspected by cortical neuroanatomists, the same basic laminar and tangential organization of the excitatory neurons of the neocortex is evident wherever it has been sought. Similarly, the inhibitory neurons show characteristic morphology and patterns of connections throughout the neocortex. We offer a simple model of cortical processing that is consistent with the major features of cortical circuits: The superficial layer neurons within local patches of cortex, and within areas, cooperate to explore all possible interpretations of different cortical input and cooperatively select an interpretation consistent with their various cortical and subcortical inputs.
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    URL: http://dx.doi.org/10.1146/annurev.neuro.27.070203.144152
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    THE MIRROR-NEURON SYSTEM (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 27 (2004), S. 169-192 
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    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: A category of stimuli of great importance for primates, humans in particular, is that formed by actions done by other individuals. If we want to survive, we must understand the actions of others. Furthermore, without action understanding, social organization is impossible. In the case of humans, there is another faculty that depends on the observation of others' actions: imitation learning. Unlike most species, we are able to learn by imitation, and this faculty is at the basis of human culture. In this review we present data on a neurophysiological mechanism-the mirror-neuron mechanism-that appears to play a fundamental role in both action understanding and imitation. We describe first the functional properties of mirror neurons in monkeys. We review next the characteristics of the mirror-neuron system in humans. We stress, in particular, those properties specific to the human mirror-neuron system that might explain the human capacity to learn by imitation. We conclude by discussing the relationship between the mirror-neuron system and language.
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    URL: http://dx.doi.org/10.1146/annurev.neuro.27.070203.144230
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    GENETIC APPROACHES TO THE STUDY OF ANXIETY (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 27 (2004), S. 193-222 
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    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Anxiety and its disorders have long been known to be familial. Recently, genetic approaches have been used to clarify the role of heredity in the development of anxiety and to probe its neurobiological underpinnings. Twin studies have shown that a significant proportion of the liability to develop any given anxiety disorder is due to genetic factors. Ongoing efforts to map anxiety-related loci in both animals and humans are underway with limited success to date. Animal models have played a large role in furthering our understanding of the genetic basis of anxiety, demonstrating that the genetic factors underlying anxiety are complex and varied. Recent advances in molecular genetic techniques have allowed increasing specificity in the manipulation of gene expression within the central nervous system of the mouse. With this increasing specificity has come the ability to ask and answer precise questions about the mechanisms of anxiety and its treatment.
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    URL: http://dx.doi.org/10.1146/annurev.neuro.27.070203.144212
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    UBIQUITIN-DEPENDENT REGULATION OF THE SYNAPSE (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 27 (2004), S. 223-246 
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    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Posttranslational modification of cellular proteins by the covalent attachment of ubiquitin regulates protein stability, activity, and localization. Ubiquitination is rapid and reversible and is a potent mechanism for the spatial and temporal control of protein activity. By sculpting the molecular composition of the synapse, this versatile posttranslational modification shapes the pattern, activity, and plasticity of synaptic connections. Synaptic processes regulated by ubiquitination, as well as ubiquitination enzymes and their targets at the synapse, are being identified by genetic, biochemical, and electrophysiological analyses. This work provides tantalizing hints that neuronal activity collaborates with ubiquitination pathways to regulate the structure and function of synapses.
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    CELLULAR MECHANISMS OF NEURONAL POPULATION OSCILLATIONS IN THE HIPPOCAMPUS IN VITRO (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 27 (2004), S. 247-278 
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    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: A variety of population oscillations, at frequencies ~5 Hz up to 200 Hz and above, can be induced in hippocampal slices either by (a) manipulation of the ionic environment, or (b) by stimulation of metabotropic receptors; brief oscillations can even occur spontaneously. In this review, we consider in vitro theta (4-12 Hz), gamma/beta (15-70 Hz), and very fast oscillations (VFO) (〉70 Hz). Many in vitro oscillations are gated by synaptic inhibition but are influenced by electrical coupling as well; one type depends solely on electrical coupling. For some oscillations dependent upon inhibition, the detailed firing patterns of interneurons can influence long-range synchronization. Two sorts of electrical coupling are important in modulating or generating various in vitro oscillations: (a) between interneurons, primarily between dendrites; and (b) between axons of pyramidal neurons. VFO can exist in isolation or can act as generators of gamma frequency oscillations. Oscillations at gamma frequencies and below probably create conditions under which synaptic plasticity can occur, between selected neurons-even those separated by significant axonal conduction delays.
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    THE NEURAL BASIS OF TEMPORAL PROCESSING (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 27 (2004), S. 307-340 
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    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: A complete understanding of sensory and motor processing requires characterization of how the nervous system processes time in the range of tens to hundreds of milliseconds (ms). Temporal processing on this scale is required for simple sensory problems, such as interval, duration, and motion discrimination, as well as complex forms of sensory processing, such as speech recognition. Timing is also required for a wide range of motor tasks from eyelid conditioning to playing the piano. Here we review the behavioral, electrophysiological, and theoretical literature on the neural basis of temporal processing. These data suggest that temporal processing is likely to be distributed among different structures, rather than relying on a centralized timing area, as has been suggested in internal clock models. We also discuss whether temporal processing relies on specialized neural mechanisms, which perform temporal computations independent of spatial ones. We suggest that, given the intricate link between temporal and spatial information in most sensory and motor tasks, timing and spatial processing are intrinsic properties of neural function, and specialized timing mechanisms such as delay lines, oscillators, or a spectrum of different time constants are not required. Rather temporal processing may rely on state-dependent changes in network dynamics.
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    URL: http://dx.doi.org/10.1146/annurev.neuro.27.070203.144247
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    E PLURIBUS UNUM, EX UNO PLURA1: Quantitative and Single-Gene Perspectives on the Study of Behavior (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 27 (2004), S. 79-105 
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    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Genetic studies of behavior have traditionally come in two flavors: quantitative genetic studies of natural variants and single-gene studies of induced mutants. Each employed different techniques and methods of analysis toward the common, ultimate goal of understanding how genes influence behavior. With the advent of new genomic technologies, and also the realization that mechanisms underlying behavior involve a considerable degree of complex gene interaction, the traditionally separate strands of behavior genetics are merging into a single, synthetic strategy.
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    URL: http://dx.doi.org/10.1146/annurev.neuro.27.070203.144323
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    ADVANCES IN QUANTITATIVE ELECTROENCEPHALOGRAM ANALYSIS METHODS (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 453-495 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Quantitative electroencephalogram (qEEG) plays a significant role in EEG-based clinical diagnosis and studies of brain function. In past decades, various qEEG methods have been extensively studied. This article provides a detailed review of the advances in this field. qEEG methods are generally classified into linear and nonlinear approaches. The traditional qEEG approach is based on spectrum analysis, which hypothesizes that the EEG is a stationary process. EEG signals are nonstationary and nonlinear, especially in some pathological conditions. Various time-frequency representations and time-dependent measures have been proposed to address those transient and irregular events in EEG. With regard to the nonlinearity of EEG, higher order statistics and chaotic measures have been put forward. In characterizing the interactions across the cerebral cortex, an information theory-based measure such as mutual information is applied. To improve the spatial resolution, qEEG analysis has also been combined with medical imaging technology (e.g., CT, MR, and PET). With these advances, qEEG plays a very important role in basic research and clinical studies of brain injury, neurological disorders, epilepsy, sleep studies and consciousness, and brain function.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.040202.121601
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    FLUID MECHANICS OF HEART VALVES (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 331-362 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Valvular heart disease is a life-threatening disease that afflicts millions of people worldwide and leads to approximately 250,000 valve repairs and/or replacements each year. Malfunction of a native valve impairs its efficient fluid mechanic/hemodynamic performance. Artificial heart valves have been used since 1960 to replace diseased native valves and have saved millions of lives. Unfortunately, despite four decades of use, these devices are less than ideal and lead to many complications. Many of these complications/problems are directly related to the fluid mechanics associated with the various mechanical and bioprosthetic valve designs. This review focuses on the state-of-the-art experimental and computational fluid mechanics of native and prosthetic heart valves in current clinical use. The fluid dynamic performance characteristics of caged-ball, tilting-disc, bileaflet mechanical valves and porcine and pericardial stented and nonstented bioprostheic valves are reviewed. Other issues related to heart valve performance, such as biomaterials, solid mechanics, tissue mechanics, and durability, are not addressed in this review.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.6.040803.140111
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    BIOMATERIALS: Where We Have Been and Where We are Going (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 41-75 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Since its inception just over a half century ago, the field of biomaterials has seen a consistent growth with a steady introduction of new ideas and productive branches. This review describes where we have been, the state of the art today, and where we might be in 10 or 20 years. Herein, we highlight some of the latest advancements in biomaterials that aim to control biological responses and ultimately heal. This new generation of biomaterials includes surface modification of materials to overcome nonspecific protein adsorption in vivo, precision immobilization of signaling groups on surfaces, development of synthetic materials with controlled properties for drug and cell carriers, biologically inspired materials that mimic natural processes, and design of sophisticated three-dimensional (3-D) architectures to produce well-defined patterns for diagnostics, e.g., biological microelectromechanical systems (bioMEMs), and tissue engineering.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.6.040803.140027
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    THE NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 1-26 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.6.062403.131947
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    FRACTAL ANALYSIS OF THE VASCULAR TREE IN THE HUMAN RETINA (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 427-452 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: The retinal circulation of the normal human retinal vasculature is statistically self-similar and fractal. Studies from several groups present strong evidence that the fractal dimension of the blood vessels in the normal human retina is approximately 1.7. This is the same fractal dimension that is found for a diffusion-limited growth process, and it may have implications for the embryological development of the retinal vascular system. The methods of determining the fractal dimension for branching trees are reviewed together with proposed models for the optimal formation (Murray Principle) of the branching vascular tree in the human retina and the branching pattern of the human bronchial tree. The limitations of fractal analysis of branching biological structures are evaluated. Understanding the design principles of branching vascular systems and the human bronchial tree may find applications in tissue and organ engineering, i.e., bioartificial organs for both liver and kidney.
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    BIOMATERIALS: Where We Have Been and Where We are Going (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 41-75 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Since its inception just over a half century ago, the field of biomaterials has seen a consistent growth with a steady introduction of new ideas and productive branches. This review describes where we have been, the state of the art today, and where we might be in 10 or 20 years. Herein, we highlight some of the latest advancements in biomaterials that aim to control biological responses and ultimately heal. This new generation of biomaterials includes surface modification of materials to overcome nonspecific protein adsorption in vivo, precision immobilization of signaling groups on surfaces, development of synthetic materials with controlled properties for drug and cell carriers, biologically inspired materials that mimic natural processes, and design of sophisticated three-dimensional (3-D) architectures to produce well-defined patterns for diagnostics, e.g., biological microelectromechanical systems (bioMEMs), and tissue engineering.
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    TISSUE GROWTH AND REMODELING (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 77-107 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: The growth and remodeling of a tissue depends on certain features in the history of its mechanical environment as well as its genetic makeup. The mechanical environment influences the tissue's developing morphology, the process of simply increasing the size of existing morphological structures, and the formation of the proteins of which the tissue is constructed. The relationships between genetic information, various epigenetic mechanisms and tissue development are discussed. The developmental growth and remodeling of most structural tissues are enhanced by the use of those tissues and retarded by their disuse. The mechanical or mathematical modeling of tissue growth and development using cellular automata models and continuum mechanical models is reviewed.
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    OPTICAL PROJECTION TOMOGRAPHY (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 209-228 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Optical projection tomography is a new approach for three-dimensional (3-D) imaging of small biological specimens. It fills an imaging gap between MRI and confocal microscopy, being most suited to specimens that are from 1 to 10 mm across. The tomographic principles of optical projection tomography (OPT) are explained, its most important applications in biomedical research explored, and comparisons drawn of its pros and cons compared to a number of alternative imaging technologies.
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    Growth and Differentiation (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 31 (1969), S. 19-40 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.ph.31.030169.000315
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    A Half Century in Science and Society (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 31 (1969), S. 1-20 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
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    URL: http://dx.doi.org/10.1146/annurev.ph.31.030169.000245
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    Comparative Aspects of Muscle (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 31 (1969), S. 43-82 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
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    URL: http://dx.doi.org/10.1146/annurev.ph.31.030169.000355
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    Kidney, Water, and Electrolytes (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 31 (1969), S. 117-172 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
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    URL: http://dx.doi.org/10.1146/annurev.ph.31.030169.001001
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    Exercise (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 31 (1969), S. 85-116 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
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    URL: http://dx.doi.org/10.1146/annurev.ph.31.030169.000505
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    Digestion: Motor Function (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 31 (1969), S. 203-226 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
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    URL: http://dx.doi.org/10.1146/annurev.ph.31.030169.001223
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    Respiration (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 31 (1969), S. 173-202 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
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    URL: http://dx.doi.org/10.1146/annurev.ph.31.030169.001133
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    Blood Clotting Mechanisms: Three Basic Reactions (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 31 (1969), S. 269-294 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
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    URL: http://dx.doi.org/10.1146/annurev.ph.31.030169.001413
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    Liver: Functional Interactions Within the Intact Animal (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 31 (1969), S. 227-268 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.ph.31.030169.001303
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    Overall Circulatory Regulation (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 31 (1969), S. 295-330 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
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    URL: http://dx.doi.org/10.1146/annurev.ph.31.030169.001455
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    The Endocrine Function of the Pancreas (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 31 (1969), S. 353-382 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
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    URL: http://dx.doi.org/10.1146/annurev.ph.31.030169.002033
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    Neuroendocrine Aspects of Mammalian Reproduction (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 31 (1969), S. 383-416 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
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    URL: http://dx.doi.org/10.1146/annurev.ph.31.030169.002123
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    Somatic Sensation (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 31 (1969), S. 417-450 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
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    URL: http://dx.doi.org/10.1146/annurev.ph.31.030169.002221
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    Hemodynamics (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 31 (1969), S. 331-352 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
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    URL: http://dx.doi.org/10.1146/annurev.ph.31.030169.001555
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    Motor Mechanisms of the CNS: Cerebrocerebellar Interrelations (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 31 (1969), S. 451-498 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
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    URL: http://dx.doi.org/10.1146/annurev.ph.31.030169.002315
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    Neurophysiology of Vision (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 31 (1969), S. 499-544 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
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    URL: http://dx.doi.org/10.1146/annurev.ph.31.030169.002435
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    Comparative Physiology of Hearing (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 31 (1969), S. 545-580 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.ph.31.030169.002553
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    Cardiac Muscle: Activation and Contraction (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 31 (1969), S. 647-674 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.ph.31.030169.003243
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  • 97
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    Biological Membranes: the Physical Basis of ION and Nonelectrolyte Selectivity (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 31 (1969), S. 581-646 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.ph.31.030169.003053
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  • 98
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    Chronobiology (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 31 (1969), S. 675-726 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.ph.31.030169.003331
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  • 99
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    Some Early History of Membrane Molecular Biology (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 66 (2004), S. 1-27 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: This article is mostly about the beginnings of the molecular biology of membranes, covering the decade 1964-1974. It is difficult to read (or write) this article because of a sense of deja vu. Most of the material in it is considered commonplace today, having been established experimentally since then. But at the time this work was begun, practically nothing was known about the molecular structure and the mechanisms of the functions of membranes. This situation existed because no membrane proteins of the kind I called integral had as yet been isolated in a pure state, and therefore none had had their amino acid sequence determined. The first integral membrane protein to be so characterized was human erythrocyte glycophorin, in 1978. It was the use of the thermodynamic reasoning that had been developed for the study of water-soluble proteins, together with the information from several key experiments carried out in a number of laboratories during the early decade, that led us to the fluid mosaic model of membrane structure in 1972. Without direct evidence to confirm the model in 1971-1972, my colleagues and I nevertheless had the confidence in it to pursue some of the consequences of the model for a new understanding of many membrane functions, which I present here in some detail. Finally, I discuss two recent high-resolution X-ray crystallographic studies of integral proteins to ask how well the structural and functional proposals that we derived from the fluid mosaic model fit these remarkably detailed X-ray results.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.66.032902.131835
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  • 100
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    Mechanism of Rectification in Inward-Rectifier K+ Channels1 (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 66 (2004), S. 103-129 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Inward rectifiers are a class of K+ channels that can conduct much larger inward currents at membrane voltages negative to the K+ equilibrium potential than outward currents at voltages positive to it, even when K+ concentrations on both sides of the membrane are made equal. This conduction property, called inward rectification, enables inward rectifiers to perform many important physiological tasks. Rectification is not an inherent property of the channel protein itself, but reflects strong voltage dependence of channel block by intracellular cations such as Mg2+ and polyamines. This voltage dependence results primarily from the movement of K+ ions across the transmembrane electric field along the pore, which is energetically coupled to the blocker binding and unbinding. This mutual displacement mechanism between several K+ ions and a blocker explains the signature feature of inward rectifier K+ channels, namely, that at a given concentration of intracellular K+, their macroscopic conductance depends on the difference between membrane voltage and the K+ equilibrium potential rather than on membrane voltage itself.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.66.032102.150822
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