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  • 1
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Abstract In the last four to five years, the view that G protein-coupled receptors (GPCRs) function as monomeric proteins has been challenged by numerous studies, which suggests that GPCRs exist as dimers or even higher-structure oligomers. Recently, biophysical methods based on luminescence and fluorescence energy transfer have confirmed the existence of such oligomeric complexes in living cells. Although no consensus exists on the role of receptor dimerization, converging evidence suggests potential roles in various aspects of receptor biogenesis and function. In several cases, receptors appear to fold as constitutive dimers early after biosynthesis, whereas ligand-promoted dimerization at the cell surface has been proposed for others. The reports of heterodimerization between receptor subtypes suggest a potential level of receptor complexity that could account for previously unexpected pharmacological diversities. In addition to fundamentally changing our views on the structure and activation processes of GPCRs, the concept of homo- and heterodimerization could have dramatic impacts on drug development and screening.
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  • 2
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Medicine 54 (2003), S. 169-184 
    ISSN: 0066-4219
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine
    Notes: Abstract Clinical and biological features of patients with the idiopathic hypereosinophilic syndrome (HES) are heterogeneous. Recent evidence suggests at least two distinct underlying hematological disorders involving myeloid and lymphoid cells, respectively. We therefore suggest that the term idiopathic should be abandoned in the classification of HES. This review defines the "myeloproliferative" and "lymphocytic" variants of the HES and addresses the management of each variant, focusing on diagnosis and treatment of the newly identified lymphocytic variant.
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  • 3
    ISSN: 0066-4219
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine
    Notes: Abstract Atrial fibrillation is frequently disabling and resistant to antiarrhythmic drugs. Curative treatment by catheter-based ablation has been shown to be feasible either by achieving long linear lesions, mainly in the left atrium, or by targeting the initiating focus, most frequently in the pulmonary veins. This paper reviews the different ablation approaches, their results, potential complications, and relative merits.
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  • 4
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 24 (2001), S. 1121-1159 
    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The defining neuropathological characteristics of Alzheimer's disease are abundant filamentous tau lesions and deposits of fibrillar amyloid beta peptides. Prominent filamentous tau inclusions and brain degeneration in the absence of beta-amyloid deposits are also hallmarks of neurodegenerative tauopathies exemplified by sporadic corticobasal degeneration, progressive supranuclear palsy, and Pick's disease, as well as by hereditary frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Because multiple tau gene mutations are pathogenic for FTDP-17 and tau polymorphisms appear to be genetic risk factors for sporadic progressive supranuclear palsy and corticobasal degeneration, tau abnormalities are linked directly to the etiology and pathogenesis of neurodegenerative disease. Indeed, emerging data support the hypothesis that different tau gene mutations are pathogenic because they impair tau functions, promote tau fibrillization, or perturb tau gene splicing, thereby leading to formation of biochemically and structurally distinct aggregates of tau. Nonetheless, different members of the same kindred often exhibit diverse FTDP-17 syndromes, which suggests that additional genetic or epigenetic factors influence the phenotypic manifestations of neurodegenerative tauopathies. Although these and other hypothetical mechanisms of neurodegenerative tauopathies remain to be tested and validated, transgenic models are increasingly available for this purpose, and they will accelerate discovery of more effective therapies for neurodegenerative tauopathies and related disorders, including Alzheimer's disease.
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  • 5
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    ISSN: 0163-8998
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: This article reviews the standard-model prediction for the anomalous magnetic moment of the muon and describes recent updates of QED, electroweak, and hadronic contributions. Comparison of theory and experiment suggests a 2.4 difference if e+e hadrons data are used to evaluate the main hadronic effects, but a smaller discrepancy if hadronic decay data are employed. Implications of a deviation for "new physics" contributions, along with an outlook for future improvements in theory and experiment, are briefly discussed.
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  • 6
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 21 (2003), S. 685-711 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Dendritic cells (DCs) have several functions in innate and adaptive immunity. In addition, there is increasing evidence that DCs in situ induce antigen-specific unresponsiveness or tolerance in central lymphoid organs and in the periphery. In the thymus DCs generate tolerance by deleting self-reactive T cells. In peripheral lymphoid organs DCs also induce tolerance to antigens captured by receptors that mediate efficient uptake of proteins and dying cells. Uptake by these receptors leads to the constitutive presentation of antigens on major histocompatibility complex (MHC) class I and II products. In the steady state the targeting of DC antigen capture receptors with low doses of antigens leads to deletion of the corresponding T cells and unresponsiveness to antigenic rechallenge with strong adjuvants. In contrast, if a stimulus for DC maturation is coadministered with the antigen, the mice develop immunity, including interferon-gamma-secreting effector T cells and memory T cells. There is also new evidence that DCs can contribute to the expansion and differentiation of T cells that regulate or suppress other immune T cells. One possibility is that distinct developmental stages and subsets of DCs and T cells can account for the different pathways to peripheral tolerance, such as deletion or suppression. We suggest that several clinical situations, including autoimmunity and certain infectious diseases, can be influenced by the antigen-specific tolerogenic role of DCs.
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  • 7
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Autoreactive antibodies are etiologic agents in a number of autoimmune diseases. Like all other antibodies these antibodies are produced in developing B cells by V(D)J recombination in the bone marrow. Three mechanisms regulate autoreactive B cells: deletion, receptor editing, and anergy. Here we review the prevalence of autoantibodies in the initial antibody repertoire, their regulation by receptor editing, and the role of the recombinase proteins (RAG1 and RAG2) in this process.
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  • 8
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physical Chemistry 55 (2004), S. 585-611 
    ISSN: 0066-426X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Physics
    Notes: We review recent developments in single-molecule spectroscopy and microscopy. New optical methods provide access to the absorption, emission, or excitation spectra of single nano-objects and can determine either the positions of these objects with subwavelength accuracy or the full three-dimensional orientation of their transition dipole moments. Recent work aims at using single molecules as nanoparts or nanoelements in a variety of molecular-scale devices, from triggered sources of single photons to single-molecular switches. A prominent new direction explores the various interactions between molecules within individual multichromophoric systems obtained by chemical synthesis. These systems are the models for natural self-assembled systems such as the light-harvesting proteins of bacteria and green plants, which are currently studied on a single-molecule basis. Another important class of multichromophoric systems are conjugated polymers. The combination of microscopy with time- and frequency-resolved spectroscopy is opening a wide field of new and exciting applications to individual nano-objects.
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  • 9
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Phytopathology 41 (2003), S. 429-453 
    ISSN: 0066-4286
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Biology
    Notes: Bacteria associated with plants have been observed frequently to form assemblages referred to as aggregates, microcolonies, symplasmata, or biofilms on leaves and on root surfaces and within intercellular spaces of plant tissues. In a wide range of habitats, biofilms are purported to be microniches of conditions markedly different from those of the ambient environment and drive microbial cells to effect functions not possible alone or outside of biofilms. This review constructs a portrait of how biofilms associated with leaves, roots and within intercellular spaces influence the ecology of the bacteria they harbor and the relationship of bacteria with plants. We also consider how biofilms may enhance airborne dissemination, ubiquity and diversification of plant-associated bacteria and may influence strategies for biological control of plant disease and for assuring food safety. Trapped by a nexus, coordinates uncertain Ever expanding or contracting Cannibalistic and scavenging sorties Excavations through signs of past alliances Consensus signals sound revelry Then time warped by viscosity Genomes showing codependence A virtual microbial beach party With no curfew and no time-out A few estranged cells seeking exit options, Looking for another menagerie. David Sands, Montana State University, Bozeman, February 2003
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  • 10
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 42 (2002), S. 235-257 
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Abstract Compartmentalization of cyclic AMP-dependent protein kinase (PKA) is achieved through association with A-kinase anchoring proteins (AKAPs). AKAPs are a group of structurally diverse proteins with the common function of binding to the regulatory subunit of PKA and confining the holoenzyme to discrete locations within the cell. This mode of regulation ensures that PKA is exposed to isolated cAMP gradients, which allows for efficient catalytic activation and accurate substrate selection. Several AKAPs coordinate multiple members of signaling cascades, effectively assembling upstream activators and downstream effectors within the same macromolecular complex. Consequently, AKAPs may serve as points of integration for numerous signaling pathways. This review details the most recent advances in our understanding of the various biological functions dependent upon AKAP-anchored signaling complexes.
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