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  • Institute of Physics  (170,627)
  • National Academy of Sciences  (27,905)
  • Annual Reviews
  • Springer Science + Business Media
  • 2005-2009  (153,980)
  • 1980-1984  (52,277)
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  • 1
    Unknown
    Washington, DC : National Academy of Sciences
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  • 2
    Publication Date: 2022-05-25
    Description: Author Posting. © National Academy of Sciences, 2006. This article is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences 103 (2006): 3675-3680, doi:10.1073/pnas.0600160103.
    Description: We investigated whether the evolution of electric organs and electric signal diversity in two independently evolved lineages of electric fishes was accompanied by convergent changes on the molecular level. We found that a sodium channel gene (Nav1.4a) that is expressed in muscle in nonelectric fishes has lost its expression in muscle and is expressed instead in the evolutionarily novel electric organ in both lineages of electric fishes. This gene appears to be evolving under positive selection in both lineages, facilitated by its restricted expression in the electric organ. This view is reinforced by the lack of evidence for selection on this gene in one electric species in which expression of this gene is retained in muscle. Amino acid replacements occur convergently in domains that influence channel inactivation, a key trait for shaping electric communication signals. Some amino acid replacements occur at or adjacent to sites at which disease-causing mutations have been mapped in human sodium channel genes, emphasizing that these replacements occur in functionally important domains. Selection appears to have acted on the final step in channel inactivation, but complementarily on the inactivation "ball" in one lineage, and its receptor site in the other lineage. Thus, changes in the expression and sequence of the same gene are associated with the independent evolution of signal complexity.
    Description: This work was funded by National Institutes of Health Grant R01 NS025513 (to H.H.Z. and Y.L.) and National Science Foundation Integrative Graduate Education and Research Traineeship Program DGE-0114387 (to D.J.Z. and D.M.H.).
    Keywords: Animal communication ; Electric organ ; Channel inactivation ; Protein evolution ; Positive selection
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  • 3
    Publication Date: 2022-05-25
    Description: Author Posting. © National Academy of Sciences, 2006. This article is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences 103 (2006): 6448-6453, doi:10.1073/pnas.0600830103.
    Description: Submersible exploration of the Samoan hotspot revealed a new, 300-m-tall, volcanic cone, named Nafanua, in the summit crater of Vailulu'u seamount. Nafanua grew from the 1,000-m-deep crater floor in 〈4 years and could reach the sea surface within decades. Vents fill Vailulu'u crater with a thick suspension of particulates and apparently toxic fluids that mix with seawater entering from the crater breaches. Low-temperature vents form Fe oxide chimneys in many locations and up to 1-m-thick layers of hydrothermal Fe floc on Nafanua. High-temperature (81°C) hydrothermal vents in the northern moat (945-m water depth) produce acidic fluids (pH 2.7) with rising droplets of (probably) liquid CO2. The Nafanua summit vent area is inhabited by a thriving population of eels (Dysommina rugosa) that feed on midwater shrimp probably concentrated by anticyclonic currents at the volcano summit and rim. The moat and crater floor around the new volcano are littered with dead metazoans that apparently died from exposure to hydrothermal emissions. Acid-tolerant polychaetes (Polynoidae) live in this environment, apparently feeding on bacteria from decaying fish carcasses. Vailulu'u is an unpredictable and very active underwater volcano presenting a potential long-term volcanic hazard. Although eels thrive in hydrothermal vents at the summit of Nafanua, venting elsewhere in the crater causes mass mortality. Paradoxically, the same anticyclonic currents that deliver food to the eels may also concentrate a wide variety of nektonic animals in a death trap of toxic hydrothermal fluids.
    Description: This work was supported by the National Oceanic and Atmospheric Administration (NOAA) Oceans Exploration and the Hawaii Undersea Research Laboratory–NOAA Undersea Research Program, the National Science Foundation, the Australian Research Council, and the SERPENT program.
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  • 4
    Publication Date: 2022-05-25
    Description: Author Posting. © Annual Reviews, 2003. This article is posted here by permission of Annual Reviews for personal use, not for redistribution. The definitive version was published in Annual Review of Environment and Resources 28 (2003): 521-558, doi:10.1146/annurev.energy.28.011503.163443.
    Description: Agriculture and industrial development have led to inadvertent changes in the natural carbon cycle. As a consequence, concentrations of carbon dioxide and other greenhouse gases have increased in the atmosphere and may lead to changes in climate. The current challenge facing society is to develop options for future management of the carbon cycle. A variety of approaches has been suggested: direct reduction of emissions, deliberate manipulation of the natural carbon cycle to enhance sequestration, and capture and isolation of carbon from fossil fuel use. Policy development to date has laid out some of the general principles to which carbon management should adhere. These are summarized as: how much carbon is stored, by what means, and for how long. To successfully manage carbon for climate purposes requires increased understanding of carbon cycle dynamics and improvement in the scientific capabilities available for measurement as well as for policy needs. The specific needs for scientific information to underpin carbon cycle management decisions are not yet broadly known. A stronger dialogue between decision makers and scientists must be developed to foster improved application of scientific knowledge to decisions. This review focuses on the current knowledge of the carbon cycle, carbon measurement capabilities (with an emphasis on the continental scale) and the relevance of carbon cycle science to carbon sequestration goals.
    Description: The National Center for Atmospheric Research is supported by the National Science Foundation.
    Keywords: Carbon sequestration ; Measurement techniques ; Climate ; Kyoto protocol
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  • 5
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    Annual Reviews
    Publication Date: 2022-05-25
    Description: Author Posting. © Annual Reviews, 2006. This article is posted here by permission of Annual Reviews for personal use, not for redistribution. The definitive version was published in Annual Review of Fluid Mechanics 38 (2006): 395-425, doi:10.1146/annurev.fluid.38.050304.092129.
    Description: Over the past four decades, the combination of in situ and remote sensing observations has demonstrated that long nonlinear internal solitary-like waves are ubiquitous features of coastal oceans. The following provides an overview of the properties of steady internal solitary waves and the transient processes of wave generation and evolution, primarily from the point of view of weakly nonlinear theory, of which the Korteweg-de Vries equation is the most frequently used example. However, the oceanographically important processes of wave instability and breaking, generally inaccessible with these models, are also discussed. Furthermore, observations often show strongly nonlinear waves whose properties can only be explained with fully nonlinear models.
    Description: KRH acknowledges support from NSF and ONR and an Independent Study Award from the Woods Hole Oceanographic Institution. WKM acknowledges support from NSF and ONR, which has made his work in this area possible, in close collaboration with former graduate students at Scripps Institution of Oceanography and MIT.
    Keywords: Solitary waves ; Nonlinear waves ; Stratified flow ; Physical Oceanography
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  • 6
    Publication Date: 2022-05-25
    Description: Author Posting. © National Academy of Sciences, 2006. This article is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences 103 (2006): 3846-3851, doi:10.1073/pnas.0600035103.
    Description: Studies of deeply buried, sedimentary microbial communities and associated biogeochemical processes during Ocean Drilling Program Leg 201 showed elevated prokaryotic cell numbers in sediment layers where methane is consumed anaerobically at the expense of sulfate. Here, we show that extractable archaeal rRNA, selecting only for active community members in these ecosystems, is dominated by sequences of uncultivated Archaea affiliated with the Marine Benthic Group B and the Miscellaneous Crenarchaeotal Group, whereas known methanotrophic Archaea are not detectable. Carbon flow reconstructions based on stable isotopic compositions of whole archaeal cells, intact archaeal membrane lipids, and other sedimentary carbon pools indicate that these Archaea assimilate sedimentary organic compounds other than methane even though methanotrophy accounts for a major fraction of carbon cycled in these ecosystems. Oxidation of methane by members of Marine Benthic Group B and the Miscellaneous Crenarchaeotal Group without assimilation of methane–carbon provides a plausible explanation. Maintenance energies of these subsurface communities appear to be orders of magnitude lower than minimum values known from laboratory observations, and ecosystem-level carbon budgets suggest that community turnover times are on the order of 100–2,000 years. Our study provides clues about the metabolic functionality of two cosmopolitan groups of uncultured Archaea.
    Description: This work was supported by Deutsche Forschungsgemeinschaft (to J.S.L., R.A., M.E., and K.-U.H. at Research Center for Ocean Margins and Grant Hi 616/4 to K.U.-H.); National Aeronautics and Space Administration Astrobiology Institute Grants NNA04CC06A (to J.E.B. and C.H.H. at Pennsylvania State University), NCC 2-1275 (to M.A.L., K.G.L., K.B.S., H.F.F., A.T., and K.-U.H. at the University of Rhode Island), and NCC 2-1054 (to M.L.S. and A.T. at the Marine Biological Laboratory); the G. Unger Vetlesen Foundation; U.S. Department of Energy Grant DE-FG02-93ER20117; and NSF Grant MCB03-48492. J.F.B. was supported by NSF Integrative Graduate Education and Research Traineeship Program Grant DGE-9972759 and a Schlanger fellowship from the Joint Oceanographic Institutions (JOI). M.A.L. was supported in part by postcruise support from JOI.
    Keywords: Anaerobic methanotrophy ; Deep biosphere ; FISH–secondary ion MS ; Intact polar lipids ; Stable carbon isotopes
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  • 7
    Publication Date: 2022-05-25
    Description: Author Posting. © National Academy of Sciences, 2002. This article is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences 99 (2002): 14694-14699, doi:10.1073/pnas.232562899.
    Description: The aryl hydrocarbon receptor (AHR) is a ligand-inducible transcription factor that is best known because it mediates the actions of polycyclic and halogenated aromatic hydrocarbon environmental toxicants such as 3-methylcholanthrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin. We report here the successful identification of an endogenous ligand for this receptor; {approx}20 µg was isolated in pure form from 35 kg of porcine lung. Its structure was deduced as 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester from extensive physical measurements and quantum mechanical calculations. In a reporter gene assay, this ligand activates the AHR with a potency five times greater than that of {beta}-naphthoflavone, a prototypical synthetic AHR ligand. 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester competes with 2,3,7,8-[3H]tetrachlorodibenzo-p-dioxin for binding to human, murine, and fish AHRs, thus showing that AHR activation is caused by direct receptor binding, and that recognition of this endogenous ligand is conserved from early vertebrates (fish) to humans.
    Description: This work was supported by the Wisconsin Alumni Research Foundation, the University of Wisconsin Sea Grant Institute, and the National Institutes of Health.
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  • 8
    Publication Date: 2022-05-25
    Description: Author Posting. © National Academy of Sciences, 2006. This article is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences 103 (2006): 6252-6257, doi:10.1073/pnas.0509950103.
    Description: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related halogenated aromatic hydrocarbons (HAHs) are highly toxic to most vertebrate animals, but there are dramatic differences in sensitivity among species and strains. Aquatic birds including the common tern (Sterna hirundo) are highly exposed to HAHs in the environment, but are up to 250-fold less sensitive to these compounds than the typical avian model, the domestic chicken (Gallus gallus). The mechanism of HAH toxicity involves altered gene expression subsequent to activation of the aryl hydrocarbon receptor (AHR), a basic helix–loop–helix-PAS transcription factor. AHR polymorphisms underlie mouse strain differences in sensitivity to HAHs and polynuclear aromatic hydrocarbons, but the role of the AHR in species differences in HAH sensitivity is not well understood. Here, we show that although chicken and tern AHRs both exhibit specific binding of [3H]TCDD, the tern AHR has a lower binding affinity and exhibits a reduced ability to support TCDD-dependent transactivation as compared to AHRs from chicken or mouse. We further show through use of chimeric AHR proteins and site-directed mutagenesis that the difference between the chicken and tern AHRs resides in the ligand-binding domain and that two amino acids (Val-325 and Ala-381) are responsible for the reduced activity of the tern AHR. Other avian species with reduced sensitivity to HAHs also possess these residues. These studies provide a molecular understanding of species differences in sensitivity to dioxin-like compounds and suggest an approach to using the AHR as a marker of dioxin susceptibility in wildlife.
    Description: This research was supported by the National Oceanographic and Atmospheric Administration National Sea Grant College Program, Department of Commerce, under Grants NA46RG0470 and NA16RG2273.
    Keywords: Basic helix–loop–helix-PAS ; Comparative toxicology ; Mechanisms ; Risk assessment ; Susceptibility
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  • 9
    Publication Date: 2022-05-25
    Description: First published online as a Review in Advance on October 24, 2005. (Some corrections may occur before final publication online and in print)
    Description: Author Posting. © Annual Reviews, 2005. This article is posted here by permission of Annual Reviews for personal use, not for redistribution. The definitive version was published in Annual Review of Physiology 68 (2006): 22.1-22.29, doi:10.1146/annurev.physiol.68.040104.105418.
    Description: Superfast muscles of vertebrates power sound production. The fastest, the swimbladder muscle of toadfish, generates mechanical power at frequencies in excess of 200 Hz. To operate at these frequencies, the speed of relaxation has had to increase approximately 50-fold. This increase is accomplished by modifications of three kinetic traits: (a) a fast calcium transient due to extremely high concentration of sarcoplasmic reticulum (SR)-Ca2+ pumps and parvalbumin, (b) fast off-rate of Ca2+ from troponin C due to an alteration in troponin, and (c) fast cross-bridge detachment rate constant (g, 50 times faster than that in rabbit fast-twitch muscle) due to an alteration in myosin. Although these three modifications permit swimbladder muscle to generate mechanical work at high frequencies (where locomotor muscles cannot), it comes with a cost: The high g causes a large reduction in attached force-generating cross-bridges, making the swimbladder incapable of powering low-frequency locomotory movements. Hence the locomotory and sound-producing muscles have mutually exclusive designs.
    Description: This work was made possible by support from NIH grants AR38404 and AR46125 as well as the University of Pennsylvania Research Foundation.
    Keywords: Parvalbumin ; Ca2+ release ; Ca2+ uptake ; Cross-bridges ; Adaptation ; Sound production ; Whitman Center
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  • 10
    Publication Date: 2022-05-26
    Description: Author Posting. © National Academy of Sciences, 1997. This article is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences 94 (1997): 13743-13748.
    Description: The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor through which halogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) cause altered gene expression and toxicity. The AHR belongs to the basic helix-loop-helix/Per-ARNT-Sim (bHLH-PAS) family of transcriptional regulatory proteins, whose members play key roles in development, circadian rhythmicity, and environmental homeostasis; however, the normal cellular function of the AHR is not yet known. As part of a phylogenetic approach to understanding the function and evolutionary origin of the AHR, we sequenced the PAS homology domain of AHRs from several species of early vertebrates and performed phylogenetic analyses of these AHR amino acid sequences in relation to mammalian AHRs and 24 other members of the PAS family. AHR sequences were identified in a teleost (the killifish Fundulus heteroclitus), two elasmobranch species (the skate Raja erinacea and the dogfish Mustelus canis), and a jawless fish (the lamprey Petromyzon marinus). Two putative AHR genes, designated AHR1 and AHR2, were found both in Fundulus and Mustelus. Phylogenetic analyses indicate that the AHR2 genes in these two species are orthologous, suggesting that an AHR gene duplication occurred early in vertebrate evolution and that multiple AHR genes may be present in other vertebrates. Database searches and phylogenetic analyses identified four putative PAS proteins in the nematode Caenorhabditis elegans, including possible AHR and ARNT homologs. Phylogenetic analysis of the PAS gene family reveals distinct clades containing both invertebrate and vertebrate PAS family members; the latter include paralogous sequences that we propose have arisen by gene duplication early in vertebrate evolution. Overall, our analyses indicate that the AHR is a phylogenetically ancient protein present in all living vertebrate groups (with a possible invertebrate homolog), thus providing an evolutionary perspective to the study of dioxin toxicity and AHR function.
    Description: This work was supported in part by the National Institute of Environmental Health Sciences (Grants R29 ES06272, F32 ES05644, and P42 ES07381), the Donaldson Charitable Trust, and a Christopher Haebler Frantz Fellowship (to M.A.S.).
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  • 11
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 1 (1983), S. 87-115 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
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  • 12
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 1 (1983), S. 143-173 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
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  • 13
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 1 (1983), S. 335-359 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
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  • 14
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 1 (1983), S. 307-327 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
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  • 15
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 1 (1983), S. 439-461 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
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  • 16
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 1 (1983), S. 529-568 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
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  • 17
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    Annual Review of Immunology 23 (2005), S. 161-196 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Our views regarding the origins and functions of splenic marginal zone B cells have changed considerably over the past few years. Perspectives regarding the development and function of these cells vary considerably between investigators studying human and rodent immunology. Marginal zone B cells are now recognized to constitute a distinct naive B lymphoid lineage. Considerable progress has been made regarding the mechanisms involved in marginal zone B cell development in the mouse. Many of the molecular events that participate in the retention of this lineage of B cells in the marginal zone have been identified. Here, we discuss the functions of these cells in both innate and adaptive immunity. We also attempt to reconcile differing viewpoints regarding the generation and function of marginal zone B cells in rodents and primates.
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  • 18
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 487-513 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Helper T (Th) cellĐ??regulated B cell immunity progresses in an ordered cascade of cellular development that culminates in the production of antigen-specific memory B cells. The recognition of peptide MHC class II complexes on activated antigen-presenting cells is critical for effective Th cell selection, clonal expansion, and effector Th cell function development (Phase I). Cognate effector Th cellĐ??B cell interactions then promote the development of either short-lived plasma cells (PCs) or germinal centers (GCs) (Phase II). These GCs expand, diversify, and select high-affinity variants of antigen-specific B cells for entry into the long-lived memory B cell compartment (Phase III). Upon antigen rechallenge, memory B cells rapidly expand and differentiate into PCs under the cognate control of memory Th cells (Phase IV). We review the cellular and molecular regulators of this dynamic process with emphasis on the multiple memory B cell fates that develop in vivo.
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  • 19
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    Annual Review of Immunology 23 (2005), S. 415-445 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The proliferation and differentiation of lymphocytes are regulated by receptors localized on the cell surface. Engagement of these receptors induces the activation of intracellular signaling proteins that transmit the receptor signals to distinct targets and control the cellular responses. The first signaling proteins to be discovered in higher organisms were the products of oncogenes. For example, the kinases Src and Abelson (Abl) were originally identified as oncogenes and were later characterized as important proteins for signal transduction in various cell types, including lymphocytes. Now, as many cellular signaling molecules have been discovered and ordered into certain pathways, we can better understand why particular signaling proteins are associated with tumorigenesis. In this review, we discuss recent progress in unraveling the molecular mechanisms of signaling pathways that control the proliferation and differentiation of early B cells. We point out the concepts of auto-inhibition and subcellular localization as crucial aspects in the regulation of B cell signaling.
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  • 20
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    Annual Review of Immunology 23 (2005), S. 683-747 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Multiple sclerosis (MS) develops in young adults with a complex predisposing genetic trait and probably requires an inciting environmental insult such as a viral infection to trigger the disease. The activation of CD4+ autoreactive T cells and their differentiation into a Th1 phenotype are a crucial events in the initial steps, and these cells are probably also important players in the long-term evolution of the disease. Damage of the target tissue, the central nervous system, is, however, most likely mediated by other components of the immune system, such as antibodies, complement, CD8+ T cells, and factors produced by innate immune cells. Perturbations in immunomodulatory networks that include Th2 cells, regulatory CD4+ T cells, NK cells, and others may in part be responsible for the relapsing-remitting or chronic progressive nature of the disease. However, an important paradigmatic shift in the study of MS has occurred in the past decade. It is now clear that MS is not just a disease of the immune system, but that factors contributed by the central nervous system are equally important and must be considered in the future.
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  • 21
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    Annual Review of Immunology 23 (2005), S. 651-682 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: CD8+ T cells play a critical role in antiviral immunity by exerting direct antiviral activity against infected cells. Because of their ability to recognize all types of viral proteins, they offer the promise of providing broad immunity to viruses that evade humoral immunity by varying their surface proteins. Consequently, there is considerable interest in developing vaccines that elicit effective antiviral TCD8+ responses. Generating optimal vaccines ultimately requires rational design based on detailed knowledge of how TCD8+ are activated in vivo under natural circumstances. Here we review recent progress obtained largely by in vivo studies in mice to understand the mechanistic basis for activation of naive TCD8+ in virus infections. These studies point the way to detailed understanding and provide some key information for vaccine development, although much remains to be learned to enable truly rational vaccine design.
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  • 22
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    Annual Review of Immunology 23 (2005), S. 945-974 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The Notch pathway is gaining increasing recognition as a key regulator of developmental choices, differentiation, and function throughout the hematolymphoid system. Notch controls the generation of hematopoietic stem cells during embryonic development and may affect their subsequent homeostasis. Commitment to the T??cell lineage and subsequent stages of early thymopoiesis is critically regulated by Notch. Recent data indicate that Notch can also direct the differentiation and activity of peripheral T and B cells. Thus, the full spectrum of Notch effects is just beginning to be understood. In this review, we discuss this explosion of knowledge as well as current controversies and challenges in the field.
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  • 23
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    Annual Review of Immunology 1 (1983), S. 119-142 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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  • 24
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    Annual Review of Immunology 1 (1983), S. 211-241 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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  • 25
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 1 (1983), S. 393-422 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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  • 26
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 975-1028 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The conversion of exogenous and endogenous proteins into immunogenic peptides recognized by T lymphocytes involves a series of proteolytic and other enzymatic events culminating in the formation of peptides bound to MHC class I or class II molecules. Although the biochemistry of these events has been studied in detail, only in the past few years has similar information begun to emerge describing the cellular context in which these events take place. This review thus concentrates on the properties of antigen-presenting cells, especially those aspects of their overall organization, regulation, and intracellular transport that both facilitate and modulate the processing of protein antigens. Emphasis is placed on dendritic cells and the specializations that help account for their marked efficiency at antigen processing and presentation both in vitro and, importantly, in vivo. How dendritic cells handle antigens is likely to be as important a determinant of immunogenicity and tolerance as is the nature of the antigens themselves.
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  • 27
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 515-548 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The discovery of new functions for the original B7 family members, together with the identification of additional B7 and CD28 family members, have revealed new ways in which the B7:CD28 family regulates T cell activation and tolerance. B7-1/B7-2:CD28 interactions not only promote initial T cell activation but also regulate self-tolerance by supporting CD4+CD25+ T regulatory cell homeostasis. CTLA-4 can exert its inhibitory effects in both B7-1/B7-2 dependent and independent fashions. B7-1 and B7-2 can signal bidirectionally by engaging CD28 and CTLA-4 on T cells and by delivering signals into B7-expressing cells. The five new B7 family members, ICOS ligand, PD-L1 (B7-H1), PD-L2 (B7-DC), B7-H3, and B7-H4 (B7x/B7-S1) are expressed on professional antigen-presenting cells as well as on cells within nonlymphoid organs, providing new means for regulating T cell activation and tolerance in peripheral tissues. The new CD28 families members, ICOS, PD-1, and BTLA, are inducibly expressed on T cells, and they have important roles in regulating previously activated T cells. PD-1 and BTLA also are expressed on B cells and may have broader immunoregulatory functions. The ICOS:ICOSL pathway appears to be particularly important for stimulating effector T cell responses and T cellĐ??dependent B cell responses, but it also has an important role in regulating T cell tolerance. In addition, the PD-1:PD-L1/PD-L2 pathway plays a critical role in regulating T cell activation and tolerance. In this review, we revisit the roles of the B7:CD28 family members in regulating immune responses, and we discuss their therapeutic potential.
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 26 (2005), S. 877-900 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Natural killer T (NKT) cells constitute a conserved T cell sublineage with unique properties, including reactivity for a synthetic glycolipid presented by CD1d, expression of an invariant T cell antigen receptor (TCR) ʼ̛ chain, and unusual requirements for thymic selection. They rapidly produce many cytokines after stimulation and thus influence diverse immune responses and pathogenic processes. Because of intensive research effort, we have learned much about factors promoting the development and survival of NKT cells, regulation of their cytokine production, and the means by which they influence dendritic cells and other cell types. Despite this progress, knowledge of the natural antigen(s) they recognize and their physiologic role remain incomplete. The activation of NKT cells paradoxically can lead either to suppression or stimulation of immune responses, and we cannot predict which will occur. Despite this uncertainty, many investigators are hopeful that immune therapies can be developed based on NKT cell stimulation.
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    Annual Review of Immunology 23 (2005), S. 549-600 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The Tec family tyrosine kinases are now recognized as important mediators of antigen receptor signaling in lymphocytes. Three members of this family, Itk, Rlk, and Tec, are expressed in T cells and activated in response to T cell receptor (TCR) engagement. Although initial studies demonstrated a role for these proteins in TCR-mediated activation of phospholipase C-??, recent data indicate that Tec family kinases also regulate actin cytoskeletal reorganization and cellular adhesion following TCR stimulation. In addition, Tec family kinases are activated downstream of G proteinĐ??coupled chemokine receptors, where they play parallel roles in the regulation of Rho GTPases, cell polarization, adhesion, and migration. In all these systems, however, Tec family kinases are not essential signaling components, but instead function to modulate or amplify signaling pathways. Although they quantitatively reduce proximal signaling, mutations that eliminate Tec family kinases in T cells nonetheless qualitatively alter T cell development and differentiation.
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    Notes: The immune response to the malaria parasite is complex and poorly understood. Although antibodies and T cells can control parasite growth in model systems, natural immunity to malaria in regions of high endemicity takes several years to develop. Variation and polymorphism of antibody target antigens are known to impede immune responses, but these factors alone cannot account for the slow acquisition of immunity. In human and animal model systems, cell-mediated responses can control parasite growth effectively, but such responses are regulated by parasite load via direct effects on dendritic cells and possibly on T and B cells as well. Furthermore, high parasite load is associated with pathology, and cell-mediated responses may also harm the host. Inflammatory cytokines have been implicated in the pathogenesis of cerebral malaria, anemia, weight loss, and respiratory distress in malaria. Immunity without pathology requires rapid parasite clearance, effective regulation of the inflammatory antiparasite effects of cellular responses, and the eventual development of a repertoire of antibodies effective against multiple strains. Data suggest that this may be hastened by exposure to malaria antigens in low dose, leading to augmented cellular immunity and rapid parasite clearance.
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    Annual Review of Immunology 23 (2005), S. 23-68 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Several members of the tumor necrosis factor receptor (TNFR) family function after initial T cell activation to sustain T cell responses. This review focuses on CD27, 4-1BB (CD137), OX40 (CD134), HVEM, CD30, and GITR, all of which can have costimulatory effects on T cells. The effects of these costimulatory TNFR family members can often be functionally, temporally, or spatially segregated from those of CD28 and from each other. The sequential and transient regulation of T cell activation/survival signals by different costimulators may function to allow longevity of the response while maintaining tight control of T cell survival. Depending on the disease condition, stimulation via costimulatory TNF family members can exacerbate or ameliorate disease. Despite these complexities, stimulation or blockade of TNFR family costimulators shows promise for several therapeutic applications, including cancer, infectious disease, transplantation, and autoimmunity.
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    Annual Review of Immunology 23 (2005), S. 447-485 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Autoimmunity is a complex process that likely results from the summation of multiple defective tolerance mechanisms. The NOD mouse strain is an excellent model of autoimmune disease and an important tool for dissecting tolerance mechanisms. The strength of this mouse strain is that it develops spontaneous autoimmune diabetes, which shares many similarities to autoimmune or type 1a diabetes (T1D) in human subjects, including the presence of pancreas-specific autoantibodies, autoreactive CD4+ and CD8+ T cells, and genetic linkage to disease syntenic to that found in humans. During the past ten years, investigators have used a wide variety of tools to study these mice, including immunological reagents and transgenic and knockout strains; these tools have tremendously enhanced the study of the fundamental disease mechanisms. In addition, investigators have recently developed a number of therapeutic interventions in this animal model that have now been translated into human therapies. In this review, we summarize many of the important features of disease development and progression in the NOD strain, emphasizing the role of central and peripheral tolerance mechanisms that affect diabetes in these mice. The information gained from this highly relevant model of human disease will lead to potential therapies that may alter the development of the disease and its progression in patients with T1D.
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    Annual Review of Immunology 23 (2005), S. 101-125 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Recent studies have demonstrated that cell membranes provide a unique environment for protein-protein and protein-lipid interactions that are critical for the assembly and function of the T cell receptor (TCR)-CD3 complex. Highly specific polar interactions among transmembrane (TM) domains that are uniquely favorable in the lipid environment organize the association of the three signaling dimers with the TCR. Each of these three assembly steps depends on the formation of a three-helix interface between one basic and two acidic residues in the membrane environment. The same polar TM residues that drive assembly also play a central role in quality control and export by directing the retention and degradation of free subunits and partial complexes, while membrane proximal cytoplasmic signals control recycling and degradation of surface receptors. Recent studies also suggest that interactions between the membrane and the cytoplasmic domains of CD3 proteins may be important for receptor triggering.
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    Annual Review of Immunology 2 (1984), S. 199-218 
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    Annual Review of Environment and Resources 5 (1980), S. 61-88 
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 1 (1983), S. 569-607 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 1 (1983), S. 633-655 
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 1 (1983), S. 33-62 
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 1 (1983), S. 273-306 
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 1 (1983), S. 361-388 
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 1 (1983), S. 423-438 
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    Annual Review of Immunology 1 (1983), S. 499-528 
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 1 (1983), S. 609-632 
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    Annual Review of Pharmacology 45 (2005), S. 1-25 
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: The author describes studies that led to the resolution and reconstitution of the cytochrome P450 enzyme system in microsomal membranes. The review indicates how purification and characterization of the cytochromes led to rigorous evidence for multiple isoforms of the oxygenases with distinct chemical and physical properties and different but somewhat overlapping substrate specificities. Present knowledge of the individual steps in the P450 and reductase reaction cycles is summarized, including evidence for the generation of multiple functional oxidants that may contribute to the exceptional diversity of the reactions catalyzed.
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    Annual Review of Pharmacology 45 (2005), S. 51-88 
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: This review describes the three mammalian glutathione transferase (GST) families, namely cytosolic, mitochondrial, and microsomal GST, the latter now designated MAPEG. Besides detoxifying electrophilic xenobiotics, such as chemical carcinogens, environmental pollutants, and antitumor agents, these transferases inactivate endogenous ʼ̛,?‚-unsaturated aldehydes, quinones, epoxides, and hydroperoxides formed as secondary metabolites during oxidative stress. These enzymes are also intimately involved in the biosynthesis of leukotrienes, prostaglandins, testosterone, and progesterone, as well as the degradation of tyrosine. Among their substrates, GSTs conjugate the signaling molecules 15-deoxy-??12,14-prostaglandin J2 (15d-PGJ2) and 4-hydroxynonenal with glutathione, and consequently they antagonize expression of genes trans-activated by the peroxisome proliferator-activated receptor ?? (PPAR??) and nuclear factor-erythroid 2 p45-related factor 2 (Nrf2). Through metabolism of 15d-PGJ2, GST may enhance gene expression driven by nuclear factor-?”B (NF-?”B). Cytosolic human GST exhibit genetic polymorphisms and this variation can increase susceptibility to carcinogenesis and inflammatory disease. Polymorphisms in human MAPEG are associated with alterations in lung function and increased risk of myocardial infarction and stroke. Targeted disruption of murine genes has demonstrated that cytosolic GST isoenzymes are broadly cytoprotective, whereas MAPEG proteins have proinflammatory activities. Furthermore, knockout of mouse GSTA4 and GSTZ1 leads to overexpression of transferases in the Alpha, Mu, and Pi classes, an observation suggesting they are part of an adaptive mechanism that responds to endogenous chemical cues such as 4-hydroxynonenal and tyrosine degradation products. Consistent with this hypothesis, the promoters of cytosolic GST and MAPEG genes contain antioxidant response elements through which they are transcriptionally activated during exposure to Michael reaction acceptors and oxidative stress.
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    Annual Review of Pharmacology 45 (2005), S. 177-202 
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: The importance of reactive metabolites in the pathogenesis of drug-induced toxicity has been a focus of research interest since pioneering investigations in the 1950s revealed the link between toxic metabolites and chemical carcinogenesis. There is now a great deal of evidence that shows that reactive metabolites are formed from drugs known to cause hepatotoxicity, but how these toxic species initiate and propagate tissue damage is still poorly understood. This review summarizes the evidence for reactive metabolite formation from hepatotoxic drugs, such as acetaminophen, tamoxifen, diclofenac, and troglitazone, and the current hypotheses of how this leads to liver injury. Several hepatic proteins can be modified by reactive metabolites, but this in general equates poorly with the extent of toxicity. Much more important may be the identification of the critical proteins modified by these toxic species and how this alters their function. It is also important to note that the toxicity of reactive metabolites may be mediated by noncovalent binding mechanisms, which may also have profound effects on normal liver physiology. Technological developments in the wake of the genomic revolution now provide unprecedented power to characterize and quantify covalent modification of individual target proteins and their functional consequences; such information should dramatically improve our understanding of drug-induced hepatotoxic reactions.
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    Annual Review of Pharmacology 45 (2005), S. 291-310 
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: The cytochrome P450 monooxygenases (CYPs) are the dominant enzyme system responsible for xenobiotic detoxification and drug metabolism. Several CYP isoforms exhibit non-Michaelis-Menten, or "atypical," steady state kinetic patterns. The allosteric kinetics confound prediction of drug metabolism and drug-drug interactions, and they challenge the theoretical paradigms of allosterism. Both homotropic and heterotropic ligand effects are now widely documented. It is becoming apparent that multiple ligands can simultaneously bind within the active sites of individual CYPs, and the kinetic parameters change with ligand occupancy. In fact, the functional effect of any specific ligand as an activator or inhibitor can be substrate dependent. Divergent approaches, including kinetic modeling and X-ray crystallography, are providing new information about how multiple ligand binding yields complex CYP kinetics.
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    Annual Review of Pharmacology 45 (2005), S. 335-355 
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Recent discoveries of novel and potentially important biological activity have spurred interest in the chemistry and biochemistry of nitroxyl (HNO). It has become clear that, among all the nitrogen oxides, HNO is unique in its chemistry and biology. Currently, the intimate chemical details of the biological actions of HNO are not well understood. Moreover, many of the previously accepted chemical properties of HNO have been recently revised, thus requiring reevaluation of possible mechanisms of biological action. Herein, we review these developments in HNO chemistry and biology.
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    Annual Review of Pharmacology 45 (2005), S. 385-412 
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Adenosine and its receptors have been the topic of many recent reviews ( 1Đ??26 ). These reviews provide a good summary of much of the relevant literatureĐ??including the older literature. We have, therefore, chosen to focus the present review on the insights gained from recent studies on genetically modified mice, particularly with respect to the function of adenosine receptors and their potential as therapeutic targets. The information gained from studies of drug effects is discussed in this context, and discrepancies between genetic and pharmacological results are highlighted.
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    Annual Review of Pharmacology 45 (2005), S. 657-687 
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Cardiac fibroblasts play a central role in the maintenance of extracellular matrix in the normal heart and as mediators of inflammatory and fibrotic myocardial remodeling in the injured and failing heart. In this review, we evaluate the cardiac fibroblast as a therapeutic target in heart disease. Unique features of cardiac fibroblast cell biology are discussed in relation to normal and pathophysiological cardiac function. The contribution of cardiac fibrosis as an independent risk factor in the outcome of heart failure is considered. Candidate drug therapies that derive benefit from actions on cardiac fibroblasts are summarized, including inhibitors of angiotensin-aldosterone systems, endothelin receptor antagonists, statins, anticytokine therapies, matrix metalloproteinase inhibitors, and novel antifibrotic/anti-inflammatory agents. These findings point the way to future challenges in cardiac fibroblast biology and pharmacotherapy.
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    Annual Review of Pharmacology 46 (2006), S. 65-100 
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: This review summarizes recent information concerning the pharmacological and toxicological significance of the human flavin-containing monooxygenase (FMO, EC 1.14.13.8). The human FMO oxygenates nucleophilic heteroatom-containing chemicals and drugs and generally converts them into harmless, polar, readily excreted metabolites. Sometimes, however, FMO bioactivates chemicals into reactive materials that can cause toxicity. Most of the interindividual differences of FMO are due to genetic variability and allelic variation, and splicing variants may contribute to interindividual and interethnic variability observed for FMO-mediated metabolism. In contrast to cytochrome P450 (CYP), FMO is not easily induced nor readily inhibited, and potential adverse drug-drug interactions are minimized for drugs prominently metabolized by FMO. These properties may provide advantages in drug design and discovery, and by incorporating FMO detoxication pathways into drug candidates, more drug-like materials may be forthcoming. Although exhaustive examples are not available, physiological factors can influence FMO function, and this may have implications for the clinical significance of FMO and a role in human disease.
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