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  • Annual Reviews
  • 2000-2004  (962)
  • 1980-1984
  • 2003  (962)
  • 1
    Electronic Resource
    Electronic Resource
    REGULATION OF TRP CHANNELS VIA LIPID SECOND MESSENGERS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 735-759 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract In Drosophila photoreceptors, the light-sensitive current is mediated downstream of phospholipase C by TRP (transient receptor potential) channels. Recent evidence suggests that Drosophila TRP channels are activated by diacylglycerol (DAG) or its metabolites (polyunsaturated fatty acids), possibly in combination with the reduction in phosphatidyl inositol 4,5 bisphosphate (PIP2). Consistent with this view, diacylglycerol kinase is identified as a key enzyme required for response termination. Signaling is critically dependent upon efficient PIP2 synthesis; mutants of this pathway in combination with genetically targeted PIP2 reporters provide unique insights into the kinetics and regulation of PIP2 turnover. Recent evidence indicates that a growing number of mammalian TRP homologues are also regulated by lipid messengers, including DAG, arachidonic acid, and PIP2.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.65.092101.142505
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  • 2
    Electronic Resource
    Electronic Resource
    AMINOPHOSPHOLIPID ASYMMETRY: A Matter of Life and Death (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 701-734 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract Maintenance of membrane lipid asymmetry is a dynamic process that influences many events over the lifespan of the cell. With few exceptions, most cells restrict the bulk of the aminophospholipids to the inner membrane leaflet by means of specific transporters. Working in concert with each other, these proteins correct for sporadic incursions of the aminophospholipids to the outer membrane leaflet as a result of bilayer imbalances created by various cellular events. A shift in the relative contribution in each of these activities can result in sustained exposure of the aminophospholipids at the cell surface, which allows capture of the cells by phagocytes before the integrity of the plasma membrane is compromised. The absence of an efficient recognition and elimination mechanism can result in uncontrolled and persistent presentation of self-antigens to the immune system, with development of autoimmune syndromes. To prevent this, phagocytes have developed a diverse array of distinct and redundant receptor systems that drive the postphagocytic events along pathways that facilitate cross-talk between the homeostatic and the immune systems. In this work, we review the basis for the proposed mechanism(s) by which apoptotic ligands appear on the target cell surface and the phagocyte receptors that recognize these moieties.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.65.092101.142459
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  • 3
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    PHOSPHOINOSITIDE REGULATION OF THE ACTIN CYTOSKELETON (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 761-789 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract Phosphoinositides [PPIs, which collectively refer to phosphorylated derivatives of phosphatidylinositol (PI)] have a pivotal role as precursors to important second messengers and as bona fide signaling and scaffold targeting molecules. This review focuses on recent advances that elucidate how PPIs, particularly PI(4,5)P2 (PIP2), directly regulate the actin cytoskeleton in vivo by modulating the activity and targeting of actin regulatory proteins. The role of PIP2 in stimulating actin polymerization and in establishing cytoskeleton-plasma membrane linkages is emphasized. In addition, the review presents tantalizing evidence that suggests how binding of selected cytoskeletal proteins to membrane PPIs may promote PPI clustering into raft lipid microdomains, alter their accessibility to other proteins, and even distort the bilayer conformation. These actions have profound implications for many other PPI-regulated membrane functions that are beginning to be uncovered, and they suggest how PPIs can mediate crosstalk between the actin cytoskeleton and an expanding spectrum of essential cellular functions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.65.092101.142517
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  • 4
    Electronic Resource
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    G PROTEIN-COUPLED RECEPTOR RHODOPSIN: A Prospectus (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 851-879 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract Rhodopsin is a retinal photoreceptor protein of bipartite structure consisting of the transmembrane protein opsin and a light-sensitive chromophore 11-cis-retinal, linked to opsin via a protonated Schiff base. Studies on rhodopsin have unveiled many structural and functional features that are common to a large and pharmacologically important group of proteins from the G protein-coupled receptor (GPCR) superfamily, of which rhodopsin is the best-studied member. In this work, we focus on structural features of rhodopsin as revealed by many biochemical and structural investigations. In particular, the high-resolution structure of bovine rhodopsin provides a template for understanding how GPCRs work. We describe the sensitivity and complexity of rhodopsin that lead to its important role in vision.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.65.092101.142611
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  • 5
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    CARDIAC HYPERTROPHY: The Good, the Bad, and the Ugly (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 45-79 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract Cardiac hypertrophy is the heart's response to a variety of extrinsic and intrinsic stimuli that impose increased biomechanical stress. While hypertrophy can eventually normalize wall tension, it is associated with an unfavorable outcome and threatens affected patients with sudden death or progression to overt heart failure. Accumulating evidence from studies in human patients and animal models suggests that in most instances hypertrophy is not a compensatory response to the change in mechanical load, but rather is a maladaptive process. Accordingly, modulation of myocardial growth without adversely affecting contractile function is increasingly recognized as a potentially auspicious approach in the prevention and treatment of heart failure. In this review, we summarize recent insights into hypertrophic signaling and consider several novel antihypertrophic strategies. The same thing that makes you live can kill you in the end. -Neil Young
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.65.092101.142243
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  • 6
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    PROCESSIVE AND NONPROCESSIVE MODELS OF KINESIN MOVEMENT (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 161-175 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract Conventional kinesin is the prototypic member of a family of diverse proteins that use the chemical energy of ATP hydrolysis to generate force and move along microtubules. These proteins, which are involved in a wide range of cellular functions, have been identified in protozoa, fungi, plants, and animals and possess a high degree of sequence conservation among species in their motor domains. The biochemical properties of kinesin and its homologues, in conjunction with the recently solved three-dimensional structures of several kinesin motors, have contributed to our understanding of the mechanism of kinesin movement along microtubules. We discuss several models for movement, including the hand-over-hand, inchworm, and biased diffusion models of processive movement, as well as models of nonprocessive movement.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.65.092101.142550
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  • 7
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    ORIGINS AND CONSEQUENCES OF MITOCHONDRIAL VARIATION IN VERTEBRATE MUSCLE (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 177-201 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract This review addresses the mechanisms by which mitochondrial structure and function are regulated, with a focus on vertebrate muscle. We consider the adaptive remodeling that arises during physiological transitions such as differentiation, development, and contractile activity. Parallels are drawn between such phenotypic changes and the pattern of change arising over evolutionary time, as suggested by interspecies comparisons. We address the physiological and evolutionary relationships between ATP production, thermogenesis, and superoxide generation in the context of mitochondrial function. Our discussion of mitochondrial structure focuses on the regulation of membrane composition and maintenance of the three-dimensional reticulum. Current studies of mitochondrial biogenesis strive to integrate muscle functional parameters with signal transduction and molecular genetics, providing insight into the origins of variation arising between physiological states, fiber types, and species.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.65.092101.142705
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  • 8
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    FUNCTIONAL GENOMICS AND THE COMPARATIVE PHYSIOLOGY OF HYPOXIA (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 203-230 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract Comparative physiology has proven a powerful approach to our understanding of how animals function under hypoxic conditions and to identifying potential adaptations to environmental oxygen levels. This review considers the potential for using a similar comparative approach with functional genomics to understand the genetic basis of such physiological processes and evolutionary adaptations. Comparative functional genomics is currently limited by genome data, which are available for only a few model organisms. However, comparative studies between model organisms of the same species having slightly different genomes (e.g., in-bred strains of laboratory rodents, transgenic mice, and consomic rats) demonstrate the types of results, as well as the analytical challenges, that are possible if comparative functional genomics is applied to more species. Results from wild and domestic animal studies suggest new models to investigate physiological and evolutionary responses to oxygen levels with functional genomics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.65.092101.142711
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  • 9
    Electronic Resource
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    APPLICATION OF MICROARRAY TECHNOLOGY IN ENVIRONMENTAL AND COMPARATIVE PHYSIOLOGY (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 231-259 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract DNA microarray technology is revolutionizing many aspects of biological research, allowing the expression of many thousands of gene transcripts to be monitored simultaneously. This provides powerful tools for the genome-wide correlation of gene transcript levels with physiological responses and alterations in physiological states. To date, microarray analyses have been applied almost exclusively to a few model species for which the abundant gene sequence data permit the fabrication of whole-genome microarrays. However, many interesting physiological traits and responses are poorly expressed or absent in model species and may be better illustrated in nonmodel organisms. Comparative approaches to understanding function traditionally focus on species that by virtue of their unusual adaptations, lifestyles, and phylogeny are particularly suited to address a specific biological process or problem. In this review, we show that microarray technology can be successfully applied to these nonmodel species and used to generate new insights of comparative and evolutionary significance into animal function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.65.092101.142716
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  • 10
    Electronic Resource
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    MAMMALIAN UREA TRANSPORTERS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 543-566 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract Urea plays a key role in the urine-concentrating mechanism. Physiologic and molecular data demonstrate that urea transport in kidney and red blood cells occurs by specific urea transporter proteins. Two gene families for facilitated urea transporters, UT-A and UT-B, and several urea transporter cDNA isoforms have been cloned from human, rat, mouse, and several non-mammalian species. Polyclonal antibodies have been generated to many of the urea transporter proteins, and several novel findings have resulted from their use in integrative animal studies. For example, (a) vasopressin increases the phosphorylation of UT-A1 in rat inner medullary collecting duct; (b) UT-A1 protein abundance is increased in the rat inner medulla during conditions in which urine-concentrating ability is reduced; and (c) urea transporters are expressed in non-renal tissues, and UT-A protein abundance is up-regulated in uremia in both liver and heart. In addition to the facilitated urea transporters, functional evidence exists for active urea transport in the kidney collecting duct. This review summarizes the physiologic evidence for the existence of facilitated and active urea transporters, the molecular biology of the facilitated urea transporter gene families and cDNAs, and integrative studies into urea transporter protein regulation, both in the kidney and in other organs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.65.092101.142638
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  • 11
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    IN PURSUIT OF CULTURE (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Anthropology 32 (2003), S. 1-12 
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    ISSN: 0084-6570
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Ethnic Sciences , Biology
    Notes: In this brief, autobiographical account, I trace the development of my intellectual and theoretical interests, especially as they relate to culture. How can we account for culture's being learned by individuals and yet apparently shared by members of a community? How do cultures as shared within communities change and evolve? How does what we know about languages, themselves a kind of cultural tradition, contribute to understanding culture and cultural evolution? Are processes of cultural and linguistic evolution analogous to those in the evolution of biological species and, if so, in what ways? How, also, do genetically based behavioral proclivities manifest themselves in social arenas that are structured by language and culture?
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.anthro.32.061002.093257
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  • 12
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    DEVELOPMENTAL BIOLOGY AND HUMAN EVOLUTION* (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Anthropology 32 (2003), S. 85-109 
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    ISSN: 0084-6570
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Ethnic Sciences , Biology
    Notes: Our understanding of developmental biology burgeoned during the last decade. This review summarizes recent advances, provides definitions and explanations of some basic principles, and does so in a way that will aid anthropologists in understanding their profound implications. Crucial concepts, such as developmental fields, selector and realizator genes, cell signaling mechanisms, and gene regulatory elements are briefly described and then integrated with the emergence of skeletal morphology. For the postcranium, a summary of events from limb bud formation, the appearance of anlagen, the expression of Hox genes, and the fundamentals of growth plate dynamics are briefly summarized. Of particular importance are revelations that bony morphology is largely determined by pattern formation, that growth foci such as physes and synovial joints appear to be regulated principally by positional information, and that variation in these fields is most likely determined by cis-regulatory elements acting on restricted numbers of anabolic genes downstream of selectors (such as Hox). The implications of these discoveries for the interpretation of both contemporary and ancient human skeletal morphology are profound. One of the most salient is that strain transduction now appears to play a much reduced role in shaping the human skeleton. Indeed, the entirety of "Wolff's Law" must now be reassessed in light of new knowledge about pattern formation. The review concludes with a brief discussion of some implications of these findings, including their impact on cladistics and homology, as well as on biomechanical and morphometric analyses of both ancient and modern human skeletal material.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.anthro.32.061002.093223
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  • 13
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    COMPLEX ADAPTIVE SYSTEMS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Anthropology 32 (2003), S. 183-204 
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    ISSN: 0084-6570
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Ethnic Sciences , Biology
    Notes: The study of complex adaptive systems, a subset of nonlinear dynamical systems, has recently become a major focus of interdisciplinary research in the social and natural sciences. Nonlinear systems are ubiquitous; as mathematician Stanislaw Ulam observed, to speak of "nonlinear science" is like calling zoology the study of "nonelephant animals" (quoted in Campbell et al. 1985, p. 374). The initial phase of research on nonlinear systems focused on deterministic chaos, but more recent studies have investigated the properties of self-organizing systems or anti-chaos. For mathematicians and physicists, the biggest surprise is that complexity lurks within extremely simple systems. For biologists, it is the idea that natural selection is not the sole source of order in the biological world. In the social sciences, it is suggested that emergence-the idea that complex global patterns with new properties can emerge from local interactions-could have a comparable impact.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.anthro.32.061002.093440
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  • 14
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    URBAN VIOLENCE AND STREET GANGS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Anthropology 32 (2003), S. 225-242 
    Details
    ISSN: 0084-6570
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Ethnic Sciences , Biology
    Notes: What causes urban street gang violence, and how can we better understand the forces that shape this type of adolescent and youth behavior? For close to a century, social researchers have taken many different paths in attempting to unravel this complex question, especially in the context of large-scale immigrant adaptation to the city. In recent decades these researchers have relied primarily on data gathered from survey quantitative approaches. This review traces some of these developments and outlines how frameworks of analysis have become more integrated and multidimensional, as ethnographic strategies have come into vogue again. For the last couple of decades, either a subculture of violence (i.e., the values and norms of the street gang embrace aggressive, violent behavior) or a routine activities (i.e., hanging around high crime areas with highly delinquent people) explanation dominated the discussion. To broaden and deepen the picture, many other factors need to be considered, such as ecological, socioeconomic, sociocultural, and sociopsychological, particularly in light of the immigrant experience. A multiple marginality framework lends itself to a holistic strategy that examines linkages within the various factors and the actions and interactions among them and notes the cumulative nature of urban street gang violence. Questions that are addressed in this more integrated framework are: Where did they settle? What jobs did they fill? How and why did their social practices and cultural values undergo transformations? When and in what ways did the social environment affect them? Finally, with whom did they interact? In sum, in highlighting the key themes and features of what constitutes urban street gang violence, this review suggests that the qualitative style that relies on holistic information adds important details to traditional quantitative data.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.anthro.32.061002.093426
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  • 15
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    THE ANTHROPOLOGY OF WELFARE "REFORM": New Perspectives on U.S. Urban Poverty in the Post-Welfare Era (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Anthropology 32 (2003), S. 315-338 
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    ISSN: 0084-6570
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Ethnic Sciences , Biology
    Notes: Anthropological research on welfare restructuring differs from most poverty research conducted by U.S. policy analysts and many other social scientists by its situating the study of welfare "reform" within an examination of the production of poverty and inequality at the center of the global system of advanced capitalism. In this review we examine urban poverty and welfare-state restructuring in relation to the ascent of neoliberalism, including the rise of market-oriented assumptions about social value, productivity, and investment that dominate civic life and public policy. We focus primarily, though not exclusively, on the United States. After a brief review of four theoretical frameworks that inform ethnographic research on welfare, we explore five approaches or themes in anthropological studies of welfare restructuring in the United States: (a) the ethnographic challenge to claims of policy success by documenting an unfolding crisis in social reproduction for the poor; (b) deconstructing the hegemonic discourse on welfare restructuring and juxtaposing it with the lived realities of impoverished households; (c) contesting and moving beyond the behaviorism of mainstream poverty research; (d) exploring the multiple perspectives of those differently situated within the welfare-state apparatus; and (e) theorizing the relationship between welfare restructuring and an eroding social citizenship of the poor. The analysis of gender, race, and, to a lesser extent, class is central to ethnographic research on welfare-state restructuring.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.anthro.32.061002.093431
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  • 16
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    ISOTOPIC ADVENTURES-Geological, Planetological, and Cosmic (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Earth and Planetary Sciences 31 (2003), S. 1-74 
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    ISSN: 0084-6597
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Geosciences , Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.earth.31.100901.141409
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  • 17
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    TROPICAL CYCLONES (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Earth and Planetary Sciences 31 (2003), S. 75-104 
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    ISSN: 0084-6597
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Geosciences , Physics
    Notes: Abstract Tropical cyclones encompass virtually every subdiscipline of geophysical fluid dynamics, including cumulus convection, boundary layers, thermodynamic cycles, surface wave dynamics, upper ocean wind-driven circulations, barotropic instability, Rossby waves, and air-sea interaction. After briefly reviewing what is known about the structure, behavior, and climatology of these fascinating storms, the author provides an overview of their physics, focusing on the unique and poorly understood nature of the air-sea interface, and discusses several of the most interesting avenues of ongoing research.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.earth.31.100901.141259
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  • 18
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    PHANEROZOIC ATMOSPHERIC OXYGEN (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Earth and Planetary Sciences 31 (2003), S. 105-134 
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    ISSN: 0084-6597
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Geosciences , Physics
    Notes: Abstract Theoretical calculations, based on both the chemical and isotopic composition of sedimentary rocks, indicate that atmospheric O2 has varied appreciably over Phanerozoic time, with a notable excursion during the Permo-Carboniferous reaching levels as high as 35% O2. This agrees with measurements of the carbon isotopic composition of fossil plants together with experiments and calculations on the effect of O2 on photosynthetic carbon isotope fractionation. The principal cause of the excursion was the rise of large vascular land plants and the consequent increased global burial of organic matter. Higher levels of O2 are consistent with the presence of Permo-Carboniferous giant insects, and preliminary experiments indicate that insect body size can increase with elevated O2. Higher O2 also may have caused more extensive, possibly catastrophic, wildfires. To check this, realistic burning experiments are needed to examine the effects of elevated O2 on fire behavior.
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    URL: http://dx.doi.org/10.1146/annurev.earth.31.100901.141329
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  • 19
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    MADAGASCAR: Heads It's a Continent, Tails It's an Island (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Earth and Planetary Sciences 31 (2003), S. 213-248 
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    ISSN: 0084-6597
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Geosciences , Physics
    Notes: Abstract Neither geologists nor biologists have a definition that is capable of classifying Madagascar unambiguously as an island or a continent; nor can they incorporate Malagasy natural history into a single model rooted in Africa or Asia. Madagascar is a microcosm of the larger continents, with a rock record that spans more than 3000 million years (Ma), during which it has been united episodically with, and divorced from, Asian and African connections. This is reflected in its Precambrian history of deep crustal tectonics and a Phanerozoic history of biodiversity that fluctuated between cosmopolitanism and parochialism. Both vicariance and dispersal events over the past 90 Ma have blended a unique endemism on Madagascar, now in decline following rapid extinctions that started about 2000 years ago.
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    URL: http://dx.doi.org/10.1146/annurev.earth.31.100901.141337
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  • 20
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    METAL-SILICATE PARTITIONING OF SIDEROPHILE ELEMENTS AND CORE FORMATION IN THE EARLY EARTH* (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Earth and Planetary Sciences 31 (2003), S. 135-174 
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    ISSN: 0084-6597
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Geosciences , Physics
    Notes: Abstract Accretion models for the Earth and terrestrial planets are based on the distribution of siderophile (iron-loving) elements between metal and silicate. Extensive experimental studies of the partitioning of these elements between metallic liquid and silicate melt have led to a better understanding and a more sophisticated application to planetary problems. Siderophile element metal/silicate partition coefficients are a function of temperature, pressure, oxygen fugacity, and metal and silicate composition. Quantification of these effects for a limited subset of siderophile elements has led to the idea that early Earth had a 700-km or deeper magma ocean. This new understanding of siderophile element partitioning has also led to applications to the kinetics of metal-silicate equilibrium, links to the timing of core formation, and a better understanding of core formation and metal-silicate equilibrium in the Moon and Mars. Key issues for future consideration include the role of water in early Earth, consideration of the core as a reservoir for noble gases and/or traditionally lithophile elements, siderophile element concentrations in the deep mantle, oxygen fugacity at high pressures, and further evaluation of the need for a late accretional veneer. The strongest approach to improving accretion models for the terrestrial planets is one that combines geochemistry, geophysics, and planetary dynamics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.earth.31.100901.145451
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  • 21
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    VOLCANIC ACTIVITY ON IO DURING THE GALILEO ERA (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Earth and Planetary Sciences 31 (2003), S. 175-211 
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    ISSN: 0084-6597
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Geosciences , Physics
    Notes: Abstract Galileo's explorations have revealed a remarkable variety of eruptive styles among Io's diverse volcanoes. Activity at hundreds of volcanic centers ranges from dormant through sporadic to continuous over the 20-year period of spacecraft observation. High temperature volcanism is common on Io, suggesting that the lavas are made up of mafic to ultramafic silicates rather than sulfur compounds. Io's largest plumes are driven by SO2 and sulfur-rich gasses vented from the silicate interior that produce prominent red pyroclastic deposits. Red deposits flag the source regions of many other ongoing or very recent eruptions. Smaller plumes are produced near the margins of active lava flows by explosive volatilization of the underlying or surrounding SO2. These plumes produce SO2 snowflakes that mantle existing topography. Io's volcanism drives significant variations in the atmosphere and plasma torus, yet most of the heat loss occurs through lava flows and by the quiet overturning of lava lakes without large-scale explosive activity. Although only a handful of Io's volcanoes have been directly observed to produce explosive eruptions, volcanic resurfacing is efficient enough to erase even small craters from Io's youthful surface.
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    THE EFFECTS OF BIOTURBATION ON SOIL PROCESSES AND SEDIMENT TRANSPORT (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Earth and Planetary Sciences 31 (2003), S. 249-273 
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    ISSN: 0084-6597
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Geosciences , Physics
    Notes: Abstract Plants and animals exploit the soil for food and shelter and, in the process, affect it in many different ways. For example, uprooted trees may break up bedrock, transport soil downslope, increase the heterogeneity of soil respiration rates, and inhibit soil horizonation. In this contribution, we review previously published papers that provide insights into the process of bioturbation. We focus particularly on studies that allow us to place bioturbation within a quantitative framework that links the form of hillslopes with the processes of sediment transport and soil production. Using geometrical relationships and data from others' work, we derive simple sediment flux equations for tree throw and root growth and decay.
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    URL: http://dx.doi.org/10.1146/annurev.earth.31.100901.141314
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    GLOBAL MANTLE TOMOGRAPHY: Progress Status in the Past 10 Years (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Earth and Planetary Sciences 31 (2003), S. 303-328 
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    ISSN: 0084-6597
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Geosciences , Physics
    Notes: Abstract We review the present status of global mantle tomography and discuss two main classes of models that have been developed in the past 10 years: P velocity models based on large datasets of travel times from the International Seismological Centre bulletins, often referred to as "high resolution" models, and S velocity models based on a combination of surface wave and hand picked body wave travel times, or waveforms, referred to as "long wavelength" models. We discuss their respective strengths and weaknesses, as well as progress in the resolution of other physical parameters, such as anisotropy, anelasticity, density, and bulk sound velocity using tomographic approaches. We present the view that future improvements in global seismic tomography require the utilization of the rich information contained in complete broadband seismic waveforms. This is presently within our reach owing to theoretical progress as well as the increase in computational power in recent years.
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    URL: http://dx.doi.org/10.1146/annurev.earth.31.091602.113555
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    THE ROLE OF DECAY AND MINERALIZATION IN THE PRESERVATION OF SOFT-BODIED FOSSILS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Earth and Planetary Sciences 31 (2003), S. 275-301 
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    ISSN: 0084-6597
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Geosciences , Physics
    Notes: Abstract Fossil deposits that preserve soft-bodied organisms provide critical evidence of the history of life. Usually, only more decay resistant materials, e.g., cuticles, survive as organic remains as a result of selective preservation and subsequent diagenesis to more resistant biopolymers. Permineralization, the permeation of tissues by mineralizing fluids, may preserve remarkable detail, particularly of plants. However, evidence of more labile tissues, e.g., muscle, normally requires the replication of their morphology by rapid in situ growth of minerals, i.e., authigenic mineralization. This process relies on the steep geochemical gradients generated by decay microbes. The minerals involved, and the level of detail preserved (which may be subcellular), depend on a number of factors, including the nature of microbial activity and amount of decay, availability of ions, and the type of organism that is fossilized. Understanding these controls is essential to determining the conditions that favor exceptional preservation.
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    PRODUCTION, ISOTOPIC COMPOSITION, AND ATMOSPHERIC FATE OF BIOLOGICALLY PRODUCED NITROUS OXIDE (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Earth and Planetary Sciences 31 (2003), S. 329-356 
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    ISSN: 0084-6597
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Geosciences , Physics
    Notes: Abstract The anthropogenic production of greenhouse gases and their consequent effects on global climate have garnered international attention for years. A remaining challenge facing scientists is to unambiguously quantify both sources and sinks of targeted gases. Microbiological metabolism accounts for the largest source of nitrous oxide (N2O), mostly due to global conversion of land for agriculture and massive usage of nitrogen-based fertilizers. A most powerful method for characterizing the sources of N2O lies in its multi-isotope signature. This review summarizes mechanisms that lead to biological N2O production and how discriminate placement of 15N into molecules of N2O occurs. Through direct measurements and atmospheric modeling, we can now place a constraint on the isotopic composition of biological sources of N2O and trace its fate in the atmosphere. This powerful interdisciplinary combination of biology and atmospheric chemistry is rapidly advancing the closure of the global N2O budget.
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    URL: http://dx.doi.org/10.1146/annurev.earth.31.110502.080901
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    PHYLOGENETIC APPROACHES TOWARD CROCODYLIAN HISTORY (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Earth and Planetary Sciences 31 (2003), S. 357-397 
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    ISSN: 0084-6597
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Geosciences , Physics
    Notes: Abstract A review of crocodylian phylogeny reveals a more complex history than might have been anticipated from a direct reading of the fossil record without consideration of phylogenetic relationships. The three main extant crocodylian lineages-Gavialoidea, Alligatoroidea, Crocodyloidea-are known from fossils in the Late Cretaceous, and the group is found nearly worldwide during the Cenozoic. Some groups have distributions that are best explained by the crossing of marine barriers during the Tertiary. Early Tertiary crocodylian faunas are phylogenetically composite, and clades tend to be morphologically uniform and geographically widespread. Later in the Tertiary, Old World crocodylian faunas are more endemic. Crocodylian phylogeneticists face numerous challenges, the most important being the phylogenetic relationships and time of divergence of the two living gharials (Gavialis gangeticus and Tomistoma schlegelii), the relationships among living true crocodiles (Crocodylus), and the relationships among caimans.
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    THE INDIAN MONSOON AND ITS VARIABILITY (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Earth and Planetary Sciences 31 (2003), S. 429-467 
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    ISSN: 0084-6597
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Geosciences , Physics
    Notes: Abstract For over 300 years, the monsoon has been viewed as a gigantic land-sea breeze. It is shown in this paper that satellite and conventional observations support an alternative hypothesis, which considers the monsoon as a manifestation of seasonal migration of the intertropical convergence zone (ITCZ). With the focus on the Indian monsoon, the mean seasonal pattern is described, and why it is difficult to simulate it is discussed. Some facets of the intraseasonal variation, such as active-weak cycles; break monsoon; and a special feature of intraseasonal variation over the region, namely, poleward propagations of the ITCZ at intervals of 2-6 weeks, are considered. Vertical moist stability is shown to be a key parameter in the variation of monthly convection over ocean and land as well as poleward propagations. Special features of the Bay of Bengal and the monsoon brought out by observations during a national observational experiment in 1999 are briefly described.
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    RECOGNIZING MANTLE PLUMES IN THE GEOLOGICAL RECORD (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Earth and Planetary Sciences 31 (2003), S. 469-523 
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    ISSN: 0084-6597
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Geosciences , Physics
    Notes: Abstract Mantle plumes are recognized by domal uplift, triple junction rifting, and especially the presence of a large igneous province (LIP), dominated in the Phanerozoic by flood basalts, and in the Proterozoic by the exposed plumbing system of dykes, sills, and layered intrusions. In the Archean, greenstone belts that contain komatiites have been linked to plumes. In addition, some carbonatites and kimberlites may originate from plumes that have stalled beneath thick lithosphere. Geochemistry and isotopes can be used to test and characterize the plume origin of LIPs. Seismic tomography and geochemistry of crustal and subcrustal xenoliths in kimberlites can identify fossil plumes. More speculatively, plumes (or clusters of plumes) have been linked with variation in the isotopic composition of marine carbonates, sea-level rise, iron formations, anoxia events, extinctions, continental breakup, juvenile crust production, magnetic superchrons, and meteorite impacts. The central region of a plume is located using the focus of a radiating dyke swarm, the distribution of komatiites and picrites, etc. The outer boundary of a plume head circumscribes the main flood basalt distribution and approximately coincides with the edge of domal uplift that causes shoaling and offlap in regional sedimentation.
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    RHEOLOGY OF GRANITIC MAGMAS DURING ASCENT AND EMPLACEMENT (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Earth and Planetary Sciences 31 (2003), S. 399-427 
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    ISSN: 0084-6597
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Geosciences , Physics
    Notes: Abstract Considerable progress has been made over the past decade in understanding the static rheological properties of granitic magmas in the continental crust. Changes in H2O content, CO2 content, and oxidation state of the interstitial melt phase have been identified as important compositional factors governing the rheodynamic behavior of the solid/fluid mixture. Although the strengths of granitic magmas over the crystallization interval are still poorly constrained, theoretical investigations suggest that during magma ascent, yield strengths of the order of 9 kPa are required to completely retard the upward flow in meter-wide conduits. In low Bagnold number magma suspensions with moderate crystal contents (solidosities 0.1 〈=phi〈= 0.3), viscous fluctuations may lead to flow differentiation by shear-enhanced diffusion. AMS and microstructural studies support the idea that granite plutons are intruded as crystal-poor liquids (phi〈= 50%), with fabric and foliation development restricted to the final stages of emplacement. If so, then these fabrics contain no information on the ascent (vertical transport) history of the magma. Deformation of a magmatic mush during pluton emplacement can enhance significantly the pressure gradient in the melt, resulting in a range of local macroscopic flow structures, including layering, crystal alignment, and other mechanical instabilities such as shear zones. As the suspension viscosity varies with stress rate, it is not clear how the timing of proposed rheological transitions formulated from simple equations for static magma suspensions applies to mixtures undergoing shear. New theories of magmas as multiphase flows are required if the full complexity of granitic magma rheology is to be resolved.
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    CATASTROPHIC FLOODING OF THE BLACK SEA (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Earth and Planetary Sciences 31 (2003), S. 525-554 
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    ISSN: 0084-6597
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Geosciences , Physics
    Notes: Abstract Decades of seabed mapping, reflection profiling, and seabed sampling reveal that throughout the past two million years the Black Sea was predominantly a freshwater lake interrupted only briefly by saltwater invasions coincident with global sea level highstand. When the exterior ocean lay below the relatively shallow sill of the Bosporus outlet, the Black Sea operated in two modes. As in the neighboring Caspian Sea, a cold climate mode corresponded with an expanded lake and a warm climate mode with a shrunken lake. Thus, during much of the cold glacial Quaternary, the expanded Black Sea's lake spilled into to the Marmara Sea and from there to the Mediterranean. However, in the warm climate mode, after receiving a vast volume of ice sheet meltwater, the shoreline of the shrinking lake contracted to the outer shelf and on a few occasions even beyond the shelf edge. If the confluence of a falling interior lake and a rising global ocean persisted to the moment when the rising ocean penetrated across the dividing sill, it would set the stage for catastrophic flooding. Although recently challenged, the flood hypothesis for the connecting event best fits the full set of observations.
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    IS EL NINO SPORADIC OR CYCLIC? (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Earth and Planetary Sciences 31 (2003), S. 579-594 
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    ISSN: 0084-6597
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Geosciences , Physics
    Notes: Abstract Is El Nino one phase of a continual, self-sustaining natural mode of the coupled ocean-atmosphere that has La Nina as the complementary phase? Or is El Nino a temporary departure from "normal" conditions "triggered" by a random disturbance such as a burst of westerly winds? A growing body of evidence-stability analyses, studies of the energetics, simulations that reproduce the statistics of sea surface temperature variations in the eastern equatorial Pacific-indicates that reality corresponds to a compromise between these two possibilities: The observed Southern Oscillation between El Nino and La Nina corresponds to a weakly damped mode that is sustained by random disturbances. This means that the predictability of El Nino is limited by the continual presence of "noise" so that forecasts should be probabilistic. The Southern Oscillation is also subject to decadal modulations. How it will be influenced by global warming is a matter of considerable uncertainty.
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    PROTOFIBRILS, PORES, FIBRILS, AND NEURODEGENERATION: Separating the Responsible Protein Aggregates from The Innocent Bystanders** (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 26 (2003), S. 267-298 
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    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Many neurodegenerative diseases, including Alzheimer's and Parkinson's and the transmissible spongiform encephalopathies (prion diseases), are characterized at autopsy by neuronal loss and protein aggregates that are typically fibrillar. A convergence of evidence strongly suggests that protein aggregation is neurotoxic and not a product of cell death. However, the identity of the neurotoxic aggregate and the mechanism by which it disables and eventually kills a neuron are unknown. Both biophysical studies aimed at elucidating the precise mechanism of in vitro aggregation and animal modeling studies support the emerging notion that an ordered prefibrillar oligomer, or protofibril, may be responsible for cell death and that the fibrillar form that is typically observed at autopsy may actually be neuroprotective. A subpopulation of protofibrils may function as pathogenic amyloid pores. An analogous mechanism may explain the neurotoxicity of the prion protein; recent data demonstrates that the disease-associated, infectious form of the prion protein differs from the neurotoxic species. This review focuses on recent experimental studies aimed at identification and characterization of the neurotoxic protein aggregates.
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    CELL-CELL SIGNALING DURING SYNAPSE FORMATION IN THE CNS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 26 (2003), S. 485-508 
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    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Synapses join individual nerve cells into a functional network. Specific cell-cell signaling events regulate synapse formation during development and thereby generate a highly reproducible connectivity pattern. The accuracy of this process is fundamental for normal brain function, and aberrant connectivity leads to nervous system disorders. However, despite the overall precision with which neuronal circuits are formed, individual synapses and synaptic networks are also plastic and can readily adapt to external stimuli or perturbations. In recent studies, several trans-synaptic signaling systems have been identified that can mediate various aspects of synaptic differentiation in the central nervous system. It appears that these individual pathways functionally cooperate, thereby generating robustness and flexibility, which ensure normal nervous system function.
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    CELL MIGRATION IN THE FOREBRAIN (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 26 (2003), S. 441-483 
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    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The forebrain comprises an intricate set of structures that are required for some of the most complex and evolved functions of the mammalian brain. As a reflection of its complexity, cell migration in the forebrain is extremely elaborated, with widespread dispersion of cells across multiple functionally distinct areas. Two general modes of migration are distinguished in the forebrain: radial migration, which establishes the general cytoarchitectonical framework of the different forebrain subdivisions; and tangential migration, which increases the cellular complexity of forebrain circuits by allowing the dispersion of multiple neuronal types. Here, we review the cellular and molecular mechanisms underlying each of these types of migrations and discuss how emerging concepts in neuronal migration are reshaping our understanding of forebrain development in normal and pathological situations.
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    NOTCH AND PRESENILIN: Regulated Intramembrane Proteolysis Links Development and Degeneration (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 26 (2003), S. 565-597 
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    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Intensive studies of three proteins-Presenilin, Notch, and the amyloid precursor protein (APP)-have led to the recognition of a direct intersection between early development and late-life neurodegeneration. Notch signaling mediates many different intercellular communication events that are essential for determining the fates of neural and nonneural cells during development and in the adult. The Notch receptor acts in a core pathway as a membrane-bound transcription factor that is released to the nucleus by a two-step cleavage mechanism called regulated intramembrane proteolysis (RIP). The second cleavage is effected by Presenilin, an unusual polytopic aspartyl protease that apparently cleaves Notch and numerous other single-transmembrane substrates within the lipid bilayer. Another Presenilin substrate, APP, releases the amyloid ss-protein that can accumulate over time in limbic and association cortices and help initiate Alzheimer's disease. Elucidating the detailed mechanism of Presenilin processing of membrane proteins is important for understanding diverse signal transduction pathways and potentially for treating and preventing Alzheimer's disease.
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    NOVEL NEURAL MODULATORS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 26 (2003), S. 105-131 
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    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The discovery that nitric oxide (NO) is produced by neurons and regulates synaptic activity has challenged the definition of a neurotransmitter. NO is not stored in synaptic vesicles and does not act at conventional receptors on the surface of adjacent neurons. The toxic gases carbon monoxide (CO) and hydrogen sulfide (H2S) are also produced by neurons and modulate synaptic activity. D-serine synthesis and release by astrocytes as an endogenous ligand for the "glycine" site of N-methyl D-aspartate (NMDA) receptors defy the concept that a neurotransmitter must be synthesized by neurons. We review the properties of these "atypical" neural modulators.
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    MOLECULAR MECHANISMS REGULATING TH1 IMMUNE RESPONSES (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 21 (2003), S. 713-758 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The T helper lymphocyte is responsible for orchestrating the appropriate immune response to a wide variety of pathogens. The recognition of the polarized T helper cell subsets Th1 and Th2 has led to an understanding of the role of these cells in coordinating a variety of immune responses, both in responses to pathogens and in autoimmune and allergic disease. Here, we discuss the mechanisms that control lineage commitment to the Th1 phenotype. What has recently emerged is a rich understanding of the cytokines, receptors, signal transduction pathways, and transcription factors involved in Th1 differentiation. Although the picture is still incomplete, the basic pathways leading to Th1 differentiation can now be understood in in vitro and a number of infection and disease models.
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    IGA FC RECEPTORS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 21 (2003), S. 177-204 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The IgA receptor family comprises a number of surface receptors including the polymeric Ig receptor involved in epithelial transport of IgA/IgM, the myeloid specific IgA Fc receptor (FcalphaRI or CD89), the Fcalpha/muR, and at least two alternative IgA receptors. These are the asialoglycoprotein receptor and the transferrin receptor, which have been implicated in IgA catabolism, and tissue IgA deposition. In this reviewwe focus on the biology of FcalphaRI (CD89). FcalphaRI is expressed on neutrophils, eosinophils, monocytes/macrophages, dendritic cells, and Kupffer cells. This receptor represents a heterogeneously glycosylated transmembrane protein that binds both IgA subclasses with low affinity. A single gene encoding FcalphaRI has been isolated, which is located within the leukocyte receptor cluster on chromosome 19. The FcalphaRI alpha chain lacks canonical signal transduction domains but can associate with the FcR gamma-chain that bears an activation motif (ITAM) in the cytoplasmic domain, allowing activatory functions. FcalphaRI expressed alone mediates endocytosis and recyling of IgA. No FcalphaRI homologue has been defined in the mouse, and progress in defining the in vivo role of FcalphaRI has been made using human FcalphaRI transgenic (Tg) mice. FcalphaRI-Tg mice demonstrated FcalphaRI expression on Kupffer cells and so defined a key role for the receptor in mucosal defense. The receptor functions as a second line of antibacterial defense involving serum IgA rather than secretory IgA. Studies in FcalphaRI-Tg mice, furthermore, defined an essential role for soluble FcalphaRI in the development of IgA nephropathy by formation of circulating IgA-FcalphaRI complexes. Finally, recent work points out a role for human IgA in treatment of infectious and neoplastic diseases.
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    T CELL ANERGY* (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 21 (2003), S. 305-334 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract T cell anergy is a tolerance mechanism in which the lymphocyte is intrinsically functionally inactivated following an antigen encounter, but remains alive for an extended period of time in a hyporesponsive state. Models of T cell anergy affecting both CD4+ and CD8+ cells fall into two broad categories. One, clonal anergy, is principally a growth arrest state, whereas the other, adaptive tolerance or in vivo anergy, represents a more generalized inhibition of proliferation and effector functions. The former arises from incomplete T cell activation, is mostly observed in previously activated T cells, is maintained by a block in the Ras/MAP kinase pathway, can be reversed by IL-2 or anti-OX40 signaling, and usually does not result in the inhibition of effector functions. The latter is most often initiated in naive T cells in vivo by stimulation in an environment deficient in costimulation or high in coinhibition. Adaptive tolerance can be induced in the thymus or in the periphery. The cells proliferate and differentiate to varying degrees and then downregulate both functions in the face of persistent antigen. The state involves an early block in tyrosine kinase activation, which predominantly inhibits calcium mobilization, and an independent mechanism that blocks signaling through the IL-2 receptor. Adaptive tolerance reverses in the absence of antigen. Aspects of both of the anergic states are found in regulatory T cells, possibly preventing them from dominating initial immune responses to foreign antigens and shutting down such responses prematurely.
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    THE REGULATORY ROLE OF Valpha14 NKT CELLS IN INNATE AND ACQUIRED IMMUNE RESPONSE (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 21 (2003), S. 483-513 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract A novel lymphocyte lineage, Valpha14 natural killer T (NKT) cells, is now well established as distinct from conventional alphabeta T cells. Valpha14 NKT cells express a single invariant Valpha14 antigen receptor that is essential for their development. Successful identification of a specific ligand, alpha-galactosylceramide(alpha-GalCer), and the establishment of gene-manipulated mice with selective loss of Valpha14 NKT cells helped elucidate the remarkable functional diversity of Valpha14 NKT cells in various immune responses such as host defense by mediating anti-nonself innate immune reaction, homeostatic regulation of anti-self responses, and antitumor immunity.
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    ON NATURAL AND ARTIFICIAL VACCINATIONS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 21 (2003), S. 515-546 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract This review summarizes the general parameters of cell- and antibody-mediated immune protection and the basic mechanisms responsible for what we call immunological memory. From this basis, the various successes and difficulties of vaccines are evaluated with respect to the role of antigen in maintaining protective immunity. Based on the fact that in humans during the first 12-48 months maternal antibodies from milk and serum protect against classical acute childhood and other infections, the concept is developed that maternal antibodies attenuate most infections of babies and infants and turn them into effective vaccines. If this "natural vaccination" under passive protective conditions does not occur, acute childhood diseases may be severe, unless infants are actively vaccinated with conventional vaccines early enough, i.e., in synchronization with the immune system's maturation. Although vaccines are available against the classical childhood diseases, they are not available for many seemingly milder childhood infections such as gastrointestinal and respiratory infections; these may eventually trigger immunopathological diseases. These changing balances between humans and infections caused by changes in nursing habits but also in hygiene levels may well be involved in changing disease patterns including increased frequencies of certain autoimmune and degenerative diseases.
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    MOLECULAR INTERACTIONS MEDIATING T CELL ANTIGEN RECOGNITION (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 21 (2003), S. 659-684 
    Details
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Over the past decade, key protein interactions contributing to T cell antigen recognition have been characterized in molecular detail. These have included interactions involving the T cell antigen receptor (TCR) itself, its coreceptors CD4 and CD8, the accessory molecule CD2, and the costimulatory receptors CD28 and CTLA-4. A clear view is emerging of how these molecules interact with their ligands at the cell-cell interface. Structural and binding studies have confirmed that the proteins span small but comparable distances and that, overall, they interact very weakly. However, there have been important surprises as well: that TCR interactions with peptide-MHC are topologically constrained and characterized by considerable conformational flexibility at the binding interface; that coreceptors engage peptide-MHC with extraordinarily fast kinetics and at angles apparently precluding direct interactions with the TCR bound to the same peptide-MHC; that the structural mechanisms allowing recognition by costimulatory and accessory molecules to be weak and yet specific are very heterogeneous; and that because of differences in both binding affinity and stoichiometry, there is enormous variation in the stability of the various costimulatory receptor/ligand complexes. These studies provide the necessary framework for exploring how these molecular interactions initiate T cell activation.
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    PLANT PEROXIREDOXINS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Plant Physiology and Plant Molecular Biology 54 (2003), S. 93-107 
    Details
    ISSN: 1040-2519
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Peroxiredoxins (Prxs) are abundant low-efficiency peroxidases located in distinct cell compartments including the chloroplast and mitochondrion. They are grouped into four clans based on their structural and biochemical properties. The catalytic center contains a cysteinyl residue that reduces diverse peroxides and is regenerated via intramolecular or intermolecular thiol-disulfide-reactions and finally by electron donors such as thioredoxins and glutaredoxins. Prxs show a complex regulation by endogenous and environmental stimuli at both the transcript and protein levels. In addition to their role in antioxidant defense in photosynthesis, respiration, and stress response, they may also be involved in modulating redox signaling during development and adaptation.
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    FROM BACTERIAL GLYCOGEN TO STARCH: Understanding the Biogenesis of the Plant Starch Granule (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Plant Physiology and Plant Molecular Biology 54 (2003), S. 207-233 
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    ISSN: 1040-2519
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Plants, green algae, and cyanobacteria synthesize storage polysaccharides by a similar ADPglucose-based pathway. Plant starch metabolism can be distinguished from that of bacterial glycogen by the presence of multiple forms of enzyme activities for each step of the pathway. This multiplicity does not coincide with any functional redundancy, as each form has seemingly acquired a distinctive and conserved role in starch metabolism. Comparisons of phenotypes generated by debranching enzyme-defective mutants in Escherichia coli and plants suggest that enzymes previously thought to be involved in polysaccharide degradation have been recruited during evolution to serve a particular purpose in starch biosynthesis. Speculations have been made that link this recruitment to the appearance of semicrystalline starch in photosynthetic eukaryotes. Besides the common core pathway, other enzymes of malto-oligosaccharide metabolism are required for normal starch metabolism. However, according to the genetic and physiological system under study, these enzymes may have acquired distinctive roles.
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    NITRIC OXIDE: The Versatility of an Extensive Signal Molecule (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Plant Physiology and Plant Molecular Biology 54 (2003), S. 109-136 
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    ISSN: 1040-2519
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Nitric oxide (NO) is a small highly diffusible gas and a ubiquitous bioactive molecule. Its chemical properties make NO a versatile signal molecule that functions through interactions with cellular targets via either redox or additive chemistry. In plants, NO plays a role in a broad spectrum of pathophysiological and developmental processes. Although nitric oxide synthase (NOS)-dependent NO production has been reported in plants, no gene, cDNA, or protein has been isolated to date. In parallel, precise and regulated NO production can be measured from the activity of the ubiquitous enzyme nitrate reductase (NR). In addition to endogenous NO formation, high NO emissions are observed from fertilized soils, but their effects on the physiology of plants are largely unknown. Many environmental and hormonal stimuli are transmitted either directly or indirectly by NO signaling cascades. The ability of NO to act simultaneously on several unrelated biochemical nodes and its redox homeostatic properties suggest that it might be a synchronizing molecule in plants.
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    PHOSPHOLIPID-BASED SIGNALING IN PLANTS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Plant Physiology and Plant Molecular Biology 54 (2003), S. 265-306 
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    ISSN: 1040-2519
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Phospholipids are emerging as novel second messengers in plant cells. They are rapidly formed in response to a variety of stimuli via the activation of lipid kinases or phospholipases. These lipid signals can activate enzymes or recruit proteins to membranes via distinct lipid-binding domains, where the local increase in concentration promotes interactions and downstream signaling. Here, the latest developments in phospholipid-based signaling are discussed, including the lipid kinases and phospholipases that are activated, the signals they produce, the domains that bind them, the downstream targets that contain them and the processes they control.
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    URL: http://dx.doi.org/10.1146/annurev.arplant.54.031902.134748
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    PERCEPTION AND SIGNAL TRANSDUCTION OF CYTOKININS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Plant Physiology and Plant Molecular Biology 54 (2003), S. 605-627 
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    ISSN: 1040-2519
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Cytokinins are plant hormones implicated in diverse and essential processes in plant growth and development, and key genes for the metabolism and actions of cytokinins have recently been identified. Cytokinins are perceived by three histidine kinases-CRE1/WOL/AHK4, AHK2, and AHK3-which initiate intracellular phosphotransfer. The final destination of the transferred phosphoryl groups is response regulators. The type-B Arabidopsis response regulators (ARRs) are DNA-binding transcriptional activators that are required for cytokinin responses. On the other hand, the type-A ARRs act as repressors of cytokinin-activated transcription. How phosphorelay regulate response regulators and how response regulators control downstream events are open questions and discussed in this review.
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    CRYPTOCHROME STRUCTURE AND SIGNAL TRANSDUCTION (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Plant Physiology and Plant Molecular Biology 54 (2003), S. 469-496 
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    ISSN: 1040-2519
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Cryptochromes are photosensory receptors mediating light regulation of growth and development in plants. Since the isolation of the Arabidopsis CRY1 gene in 1993, cryptochromes have been found in every multicellular eukaryote examined. Most plant cryptochromes have a chromophore-binding domain that shares similar structure with DNA photolyase, and a carboxyl terminal extension that contains a DQXVP-acidic-STAES (DAS) domain conserved from moss, to fern, to angiosperm. In Arabidopsis, cryptochromes are nuclear proteins that mediate light control of stem elongation, leaf expansion, photoperiodic flowering, and the circadian clock. Cryptochromes may act by interacting with proteins such as phytochromes, COP1, and clock proteins, or/and chromatin and DNA. Recent studies suggest that cryptochromes undergo a blue light-dependent phosphorylation that affects the conformation, intermolecular interactions, physiological activities, and protein abundance of the photoreceptors.
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    REMODELING THE CYTOSKELETON FOR GROWTH AND FORM: An Overview with Some New Views (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Plant Physiology and Plant Molecular Biology 54 (2003), S. 691-722 
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    ISSN: 1040-2519
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract The cytoskeleton coordinates all aspects of growth in plant cells, including exocytosis of membrane and wall components during cell expansion. This review seeks to integrate current information about cytoskeletal components in plants and the role they play in generating cell form. Advances in genome analysis have fundamentally changed the nature of research strategies and generated an explosion of new information on the cytoskeleton-associated proteins, their regulation, and their role in signaling to the cytoskeleton. Some of these proteins appear novel to plants, but many have close homologues in other eukaryotic systems. It is becoming clear that the mechanisms behind cell growth are essentially similar across the growth continuum, which ranges from tip growth to diffuse expansion. Remodeling of the actin cytoskeleton at sites of exocytosis is an especially critical feature of polarized and may also contribute to axial growth. We evaluate the most recent work on the signaling mechanisms that continually remodel the actin cytoskeleton via the activation of actin-binding proteins (ABPs) and consider the role the microtubule cytoskeleton plays in this process.
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    GENE ANNOTATION: PREDICTION AND TESTING (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genomics and Human Genetics 4 (2003), S. 69-88 
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    ISSN: 1527-8204
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Fifty years after the publication of DNA structure, the whole human genome sequence will be officially finished. This achievement marks the beginning of the task to catalogue every human gene and identify each of their function expression patterns. Currently, researchers estimate that there are about 30,000 human genes and approximately 70% of these can be automatically predicted using a combination of ab initio and similarity-based programs. However, to experimentally investigate every gene's function, the research community requires a high-quality annotation of alternative splicing, pseudogenes, and promoter regions that can only be provided by manual intervention. Manual curation of the human genome will be a long-term project as experimental data are continually produced to confirm or refine the predictions, and new features such as noncoding RNAs and enhancers have not been fully identified. Such a highly curated human gene-set made publicly available will be a great asset for the experimental community and for future comparative genome projects.
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    URL: http://dx.doi.org/10.1146/annurev.genom.4.070802.110300
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    THE DROSOPHILA MELANOGASTER GENOME (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genomics and Human Genetics 4 (2003), S. 89-117 
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    ISSN: 1527-8204
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Drosophila's importance as a model organism made it an obvious choice to be among the first genomes sequenced, and the Release 1 sequence of the euchromatic portion of the genome was published in March 2000. This accomplishment demonstrated that a whole genome shotgun (WGS) strategy could produce a reliable metazoan genome sequence. Despite the attention to sequencing methods, the nucleotide sequence is just the starting point for genome-wide analyses; at a minimum, the genome sequence must be interpreted using expressed sequence tag (EST) and complementary DNA (cDNA) evidence and computational tools to identify genes and predict the structures of their RNA and protein products. The functions of these products and the manner in which their expression and activities are controlled must then be assessed-a much more challenging task with no clear endpoint that requires a wide variety of experimental and computational methods. We first review the current state of the Drosophila melanogaster genome sequence and its structural annotation and then briefly summarize some promising approaches that are being taken to achieve an initial functional annotation.
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    SEQUENCE DIVERGENCE, FUNCTIONAL CONSTRAINT, AND SELECTION IN PROTEIN EVOLUTION (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genomics and Human Genetics 4 (2003), S. 213-235 
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    ISSN: 1527-8204
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: The genome sequences of multiple species has enabled functional inferences from comparative genomics. A primary objective is to infer biological functions from the conservation of homologous DNA sequences between species. A second, more difficult, objective is to understand what functional DNA sequences have changed over time and are responsible for species' phenotypic differences. The neutral theory of molecular evolution provides a theoretical framework in which both objectives can be explicitly tested. Development of statistical tests within this framework has provided insight into the evolutionary forces that constrain and in some cases change DNA sequences and the resulting patterns that emerge. In this article, we review recent work on how functional constraint and changes in protein function are inferred from protein polymorphism and divergence data. We relate these studies to our understanding of the neutral theory and adaptive evolution.
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    HUMAN NONSYNDROMIC SENSORINEURAL DEAFNESS* (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genomics and Human Genetics 4 (2003), S. 341-402 
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    ISSN: 1527-8204
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Given the unique biological requirements of sound transduction and the selective advantage conferred upon a species capable of sensitive sound detection, it is not surprising that up to 1% of the approximately 30,000 or more human genes are necessary for hearing. There are hundreds of monogenic disorders for which hearing loss is one manifestation of a syndrome or the only disorder and therefore is nonsyndromic. Herein we review the supporting evidence for identifying over 30 genes for dominantly and recessively inherited, nonsyndromic, sensorineural deafness. The state of knowledge concerning their biological roles is discussed in the context of the controversies within an evolving understanding of the intricate molecular machinery of the inner ear.
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    COVALENT TRAPPING OF PROTEIN-DNA COMPLEXES (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 72 (2003), S. 337-366 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract High-resolution structural studies of protein-DNA complexes have proven to be an invaluable means of understanding the diverse functions of proteins that manage the genome. Most of the structures determined to date represent proteins bound noncovalently to various DNA sequences or structures. Although noncovalent complexation is often adequate to study the structures of proteins that have robust, specific interactions with DNA, it is poorly suited to the study of transient intermediates in enzyme-catalyzed DNA processing reactions or of complexes that exist in multiple equilibrating forms. In recent years, strategies developed for the covalent trapping of protein-DNA complexes have begun to show promise as a window into an otherwise inaccessible world of structure.
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    THE ESTABLISHMENT, INHERITANCE, AND FUNCTION OF SILENCED CHROMATIN IN SACCHAROMYCES CEREVISIAE (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 72 (2003), S. 481-516 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract Genomes are organized into active regions known as euchromatin and inactive regions known as heterochromatin, or silenced chromatin. This review describes contemporary knowledge and models for how silenced chromatin in Saccharomyces cerevisiae forms, functions, and is inherited. In S. cerevisiae, Sir proteins are the key structural components of silenced chromatin. Sir proteins interact first with silencers, which dictate which regions are silenced, and then with histone tails in nucleosomes as the Sir proteins spread from silencers along chromosomes. Importantly, the spreading of silenced chromatin requires the histone deacetylase activity of Sir2p. This requirement leads to a general model for the spreading and inheritance of silenced chromatin or other special chromatin states. Such chromatin domains are marked by modifications of the nucleosomes or DNA, and this mark is able to recruit an enzyme that makes further marks. Thus, among different organisms, multiple forms of repressive chromatin can be formed using similar strategies but completely different proteins. We also describe emerging evidence that mutations that cause global changes in the modification of histones can alter the balance between euchromatin and silenced chromatin within a cell.
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    THE RNA POLYMERASE II ELONGATION COMPLEX (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 72 (2003), S. 693-715 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract Synthesis of eukaryotic mRNA by RNA polymerase II is an elaborate biochemical process that requires the concerted action of a large set of transcription factors. RNA polymerase II transcription proceeds through multiple stages designated preinitiation, initiation, and elongation. Historically, studies of the elongation stage of eukaryotic mRNA synthesis have lagged behind studies of the preinitiation and initiation stages; however, in recent years, efforts to elucidate the mechanisms governing elongation have led to the discovery of a diverse collection of transcription factors that directly regulate the activity of elongating RNA polymerase II. Moreover, these studies have revealed unanticipated roles for the RNA polymerase II elongation complex in such processes as DNA repair and recombination and the proper processing and nucleocytoplasmic transport of mRNA. Below we describe these recent advances, which highlight the important role of the RNA polymerase II elongation complex in regulation of eukaryotic gene expression.
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    THE STRUCTURAL BASIS OF LARGE RIBOSOMAL SUBUNIT FUNCTION (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 72 (2003), S. 813-850 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract The ribosome crystal structures published in the past two years have revolutionized our understanding of ribonucleoprotein structure, and more specifically, the structural basis of the peptide bonding forming activity of the ribosome. This review concentrates on the crystallographic developments that made it possible to solve these structures. It also discusses the information obtained from these structures about the three-dimensional architecture of the large ribosomal subunit, the mechanism by which it facilitates peptide bond formation, and the way antibiotics inhibit large subunit function. The work reviewed, taken as a whole, proves beyond doubt that the ribosome is an RNA enzyme, as had long been surmised on the basis of less conclusive evidence.
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    Proteomics (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 72 (2003), S. 783-812 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract Fueled by ever-growing DNA sequence information, proteomics-the large scale analysis of proteins-has become one of the most important disciplines for characterizing gene function, for building functional linkages between protein molecules, and for providing insight into the mechanisms of biological processes in a high-throughput mode. It is now possible to examine the expression of more than 1000 proteins using mass spectrometry technology coupled with various separation methods. High-throughput yeast two-hybrid approaches and analysis of protein complexes using affinity tag purification have yielded valuable protein-protein interaction maps. Large-scale protein tagging and subcellular localization projects have provided considerable information about protein function. Finally, recent developments in protein microarray technology provide a versatile tool to study protein-protein, protein-nucleic acid, protein-lipid, enzyme-substrate, and protein-drug interactions. Other types of microarrays, though not fully developed, also show great potential in diagnostics, protein profiling, and drug identification and validation. This review discusses high-throughput technologies for proteome analysis and their applications. Also discussed are the approaches used for the integrated analysis of the voluminous sets of data generated by proteome analysis conducted on a global scale.
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    THE RNA POLYMERASE II CORE PROMOTER (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 72 (2003), S. 449-479 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract The events leading to transcription of eukaryotic protein-coding genes culminate in the positioning of RNA polymerase II at the correct initiation site. The core promoter, which can extend ~35 bp upstream and/or downstream of this site, plays a central role in regulating initiation. Specific DNA elements within the core promoter bind the factors that nucleate the assembly of a functional preinitiation complex and integrate stimulatory and repressive signals from factors bound at distal sites. Although core promoter structure was originally thought to be invariant, a remarkable degree of diversity has become apparent. This article reviews the structural and functional diversity of the RNA polymerase II core promoter.
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    SIGNALS FOR SORTING OF TRANSMEMBRANE PROTEINS TO ENDOSOMES AND LYSOSOMES * (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 72 (2003), S. 395-447 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract Sorting of transmembrane proteins to endosomes and lysosomes is mediated by signals present within the cytosolic domains of the proteins. Most signals consist of short, linear sequences of amino acid residues. Some signals are referred to as tyrosine-based sorting signals and conform to the NPXY or YXXO consensus motifs. Other signals known as dileucine-based signals fit [DE]XXXL[LI] or DXXLL consensus motifs. All of these signals are recognized by components of protein coats peripherally associated with the cytosolic face of membranes. YXXO and [DE]XXXL[LI] signals are recognized with characteristic fine specificity by the adaptor protein (AP) complexes AP-1, AP-2, AP-3, and AP-4, whereas DXXLL signals are recognized by another family of adaptors known as GGAs. Several proteins, including clathrin, AP-2, and Dab2, have been proposed to function as recognition proteins for NPXY signals. YXXO and DXXLL signals bind in an extended conformation to the mu2 subunit of AP-2 and the VHS domain of the GGAs, respectively. Phosphorylation events regulate signal recognition. In addition to peptide motifs, ubiquitination of cytosolic lysine residues also serves as a signal for sorting at various stages of the endosomal-lysosomal system. Conjugated ubiquitin is recognized by UIM, UBA, or UBC domains present within many components of the internalization and lysosomal targeting machinery. This complex array of signals and recognition proteins ensures the dynamic but accurate distribution of transmembrane proteins to different compartments of the endosomal-lysosomal system.
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    TRK RECEPTORS: ROLES IN NEURONAL SIGNAL TRANSDUCTION * (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 72 (2003), S. 609-642 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract Trk receptors are a family of three receptor tyrosine kinases, each of which can be activated by one or more of four neurotrophins-nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophins 3 and 4 (NT3 and NT4). Neurotrophin signaling through these receptors regulates cell survival, proliferation, the fate of neural precursors, axon and dendrite growth and patterning, and the expression and activity of functionally important proteins, such as ion channels and neurotransmitter receptors. In the adult nervous system, the Trk receptors regulate synaptic strength and plasticity. The cytoplasmic domains of Trk receptors contain several sites of tyrosine phosphorylation that recruit intermediates in intracellular signaling cascades. As a result, Trk receptor signaling activates several small G proteins, including Ras, Rap-1, and the Cdc-42-Rac-Rho family, as well as pathways regulated by MAP kinase, PI 3-kinase and phospholipase-C-gamma (PLC-gamma). Trk receptor activation has different consequences in different cells, and the specificity of downstream Trk receptor-mediated signaling is controlled through expression of intermediates in these signaling pathways and membrane trafficking that regulates localization of different signaling constituents. Perhaps the most fascinating aspect of Trk receptor-mediated signaling is its interplay with signaling promoted by the pan-neurotrophin receptor p75NTR. p75NTR activates a distinct set of signaling pathways within cells that are in some instances synergistic and in other instances antagonistic to those activated by Trk receptors. Several of these are proapoptotic but are suppressed by Trk receptor-initiated signaling. p75NTR also influences the conformations of Trk receptors; this modifies ligand-binding specificity and affinity with important developmental consequences.
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    BIOLOGY OF THE P21-ACTIVATED KINASES (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 72 (2003), S. 743-781 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract The p21-activated kinases (PAKs) 1-3 are serine/threonine protein kinases whose activity is stimulated by the binding of active Rac and Cdc42 GTPases. Our understanding of the regulation and biology of these important signaling proteins has increased tremendously since their discovery in the mid-1990s. PAKs 1-3 are activated by a variety of GTPase-dependent and -independent mechanisms. This complexity reflects the contributions of PAK function in many cellular signaling pathways and the need to carefully control PAK action in a highly localized manner. PAKs serve as important regulators of cytoskeletal dynamics and cell motility, transcription through MAP kinase cascades, death and survival signaling, and cell-cycle progression. Consequently, PAKs have also been implicated in a number of pathological conditions and in cell transformation. We propose here a key role for PAK action in coordinating the dynamics of the actin and microtubule cytoskeletons during directional motility of cells, as well as in other functions requiring cytoskeletal polarization.
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    URL: http://dx.doi.org/10.1146/annurev.biochem.72.121801.161742
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    FEATHER MITES (ACARI: ASTIGMATA): Ecology, Behavior, and Evolution (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Entomology 48 (2003), S. 185-209 
    Details
    ISSN: 0066-4170
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Birds host many lineages of symbiotic mites, but the greatest diversity is shown by the three superfamilies of astigmatan feather mites: Analgoidea, Pterolichoidea, and Freyanoidea. Members of this diphyletic grouping have colonized all parts of the avian integument from their ancestral nidicolous habitat. Whereas some clearly feed on feather pith or skin, acting as parasites, other feather mites are paraphages and consume feather oils without causing structural damage. Sexual dimorphism in feather mites is often extreme, and little is known of the function of many elaborate male structures. Abundance and location of vane-dwelling mites is affected by season, temperature, light, humidity, and host body condition. Because transmission between hosts usually depends on host body contact, it is unsurprising that feather mite phylogeny often parallels host phylogeny; however, recent cladistic analyses have also found evidence of host-jumping and "missing the boat" in several mite lineages.
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    URL: http://dx.doi.org/10.1146/annurev.ento.48.091801.112725
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    MANIPULATION OF MEDICALLY IMPORTANT INSECT VECTORS BY THEIR PARASITES (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Entomology 48 (2003), S. 141-161 
    Details
    ISSN: 0066-4170
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Many of the most harmful parasitic diseases are transmitted by blood-feeding insect vectors. During this stage of their life cycles, selection pressures favor parasites that can manipulate their vectors to enhance transmission. Strategies may include increasing the amount of contact between vector and host, reducing vector reproductive output and consequently altering vector resource management to increase available nutrient reserves, and increasing vector longevity. Manipulation of these life-history traits may be more beneficial at some phase of the parasite's developmental process than at others. This review examines empirical, experimental, and field-based evidence to evaluate examples of changes in vector behavior and physiology that might be construed to be manipulative. Examples are mainly drawn from malaria-infected mosquitoes, Leishmania-infected sandflies, and Trypanosoma-infected tsetse flies.
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    URL: http://dx.doi.org/10.1146/annurev.ento.48.091801.112722
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    GENOMICS IN PURE AND APPLIED ENTOMOLOGY (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Entomology 48 (2003), S. 235-260 
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    ISSN: 0066-4170
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Genomics is the study of the structure and function of the genome: the set of genetic information encoded in the DNA of the nucleus and organelles of an organism. It is a dynamic field that combines traditional paths of inquiry with new approaches that would have been impossible without recent technological developments. Much of the recent focus has been on obtaining the sequence of entire genomes, determining the order and organization of the genes, and developing libraries that provide immediate physical access to any desired DNA fragment. This has enabled functional studies on a genome-wide level, including analysis of the genetic basis of complex traits, quantification of global patterns of gene expression, and systematic gene disruption projects. The successful contribution of genomics to problems in applied entomology requires the cooperation of the private and public sectors to build upon the knowledge derived from the Drosophila genome and effectively develop models for other insect Orders.
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    URL: http://dx.doi.org/10.1146/annurev.ento.48.091801.112624
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    BELOWGROUND HERBIVORY BY INSECTS: Influence on Plants and Aboveground Herbivores (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Entomology 48 (2003), S. 521-547 
    Details
    ISSN: 0066-4170
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Investigations of plant-herbivore interactions continue to be popular; however, a bias neglecting root feeders may limit our ability to understand how herbivores shape plant life histories. Root feeders can cause dramatic plant population declines, often associated with secondary stress factors such as drought or grazing. These severe impacts resulted in substantial interest in root feeders as agricultural pests and increasingly as biological weed control agents, particularly in North America. Despite logistical difficulties, establishment rates in biocontrol programs are equal or exceed those of aboveground herbivores (67.2% for aboveground herbivores, 77.5% for belowground herbivores) and root feeders are more likely to contribute to control (53.7% versus 33.6%). Models predicting root feeders would be negatively affected by competitively superior aboveground herbivores may be limited to early successional habitats or generalist root feeders attacking annual plants. In later successional habitats, root feeders become more abundant and appear to be the more potent force in driving plant performance and plant community composition. Aboveground herbivores, even at high population levels, were unable to prevent buildup of root herbivore populations and the resulting population collapse of their host plants. Significant information gaps exist about the impact of root feeders on plant physiology and secondary chemistry and their importance in natural areas, particularly in the tropics.
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    URL: http://dx.doi.org/10.1146/annurev.ento.48.091801.112700
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    LIPID RECEPTORS IN CARDIOVASCULAR DEVELOPMENT (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 23-43 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract To most people, concerns over the link between lipids and cardiovascular health most likely end with monitoring their daily consumption of dietary fats. However, it has become increasingly clear that, in addition to effects on adult cardiovascular physiology, lipids also play key roles in the formation of a functioning cardiovascular system. The lysophospholipids, lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), have come to the forefront as developmental and physiological regulators of the cardiovascular system. In this review, we discuss the function of the G protein-coupled receptors responsible for transducing LPA and S1P signals during development of the vertebrate cardiovascular system, focusing first on their role in angiogenesis and then on their function during embryonic development.
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    URL: http://dx.doi.org/10.1146/annurev.physiol.65.092101.142235
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    CELL BIOLOGY OF ACID SECRETION BY THE PARIETAL CELL (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 103-131 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract Acid secretion by the gastric parietal cell is regulated by paracrine, endocrine, and neural pathways. The physiological stimuli include histamine, acetylcholine, and gastrin via their receptors located on the basolateral plasma membranes. Stimulation of acid secretion typically involves an initial elevation of intracellular calcium and/or cAMP followed by activation of a cAMP-dependent protein kinase cascade that triggers the translocation and insertion of the proton pump enzyme, H,K-ATPase, into the apical plasma membrane of parietal cells. Whereas the H,K-ATPase contains a plasma membrane targeting motif, the stimulation-mediated relocation of the H,K-ATPase from the cytoplasmic membrane compartment to the apical plasma membrane is mediated by a SNARE protein complex and its regulatory proteins. This review summarizes the progress made toward an understanding of the cell biology of gastric acid secretion. In particular we have reviewed the early signaling events following histaminergic and cholinergic activation, the identification of multiple factors participating in the trafficking and recycling of the proton pump, and the role of the cytoskeleton in supporting the apical pole remodeling, which appears to be necessary for active acid secretion by the parietal cell. Emphasis is placed on identifying protein factors that serve as effectors for the mechanistic changes associated with cellular activation and the secretory response.
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    URL: http://dx.doi.org/10.1146/annurev.physiol.65.072302.114200
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    TRANSDUCING TOUCH IN CAENORHABDITIS ELEGANS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 429-452 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract Mechanosensation has been studied for decades, but understanding of its molecular mechanism is only now emerging from studies in Caenorhabditis elegans and Drosophila melanogaster. In both cases, the entry point proved to be genetic screens that allowed molecules needed for mechanosensation to be identified without any prior understanding of the likely components. In C. elegans, genetic screens revealed molecules needed for touch sensation along the body wall and other regions of force sensitivity. Members of two extensive membrane protein families have emerged as candidate sensory mechanotransduction channels: mec-4 and mec-10, which encode amiloride-sensitive channels (ASCs or DEG/ENaCs), and osm-9, which encodes a TRP ion channel. There are roughly 50 other members of these families whose functions in C. elegans are unknown. This article classifies these channels in C. elegans, with an emphasis on insights into their function derived from mutation. We also review the neuronal cell types in which these channels might be expressed and mediate mechanotransduction.
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    URL: http://dx.doi.org/10.1146/annurev.physiol.65.092101.142659
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    HYPERPOLARIZATION-ACTIVATED CATION CURRENTS: From Molecules to Physiological Function (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 453-480 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract Hyperpolarization-activated cation currents, termed If, Ih, or Iq, were initially discovered in heart and nerve cells over 20 years ago. These currents contribute to a wide range of physiological functions, including cardiac and neuronal pacemaker activity, the setting of resting potentials, input conductance and length constants, and dendritic integration. The hyperpolarization-activated, cation nonselective (HCN) gene family encodes the channels that underlie Ih. Here we review the relation between the biophysical properties of recombinant HCN channels and the pattern of HCN mRNA expression with the properties of native Ih in neurons and cardiac muscle. Moreover, we consider selected examples of the expanding physiological functions of Ih with a view toward understanding how the properties of HCN channels contribute to these diverse functional roles.
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    URL: http://dx.doi.org/10.1146/annurev.physiol.65.092101.142734
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    REGULATION OF Na/Pi TRANSPORTER IN THE PROXIMAL TUBULE (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 531-542 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract The physiological tuning and pathophysiological alterations of renal proximal reabsorption of inorganic phosphate can be ascribed to the net amount of the Na/Pi-cotransporter NaPi-IIa localized in the brush border membrane. The net amount of NaPi-IIa appears to be the result of an endocytotic rate regulated by a complex network of different protein kinases. New approaches demonstrated that NaPi-IIa is part of heteromeric protein complexes, organized by PDZ (postsynaptic protein PSD95, Drosophila junction protein Disc-large, tight junction protein ZO-1) proteins. Such complexes are thought to play important roles in the apical positioning and regulated endocytosis of NaPi-IIa and therefore such interactions have to be considered when explaining proximal phosphate ion reabsorption.
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    URL: http://dx.doi.org/10.1146/annurev.physiol.65.042902.092424
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    MACULA DENSA CELL SIGNALING (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 481-500 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract Macula densa cells are renal sensor elements that detect changes in distal tubular fluid composition and transmit signals to the glomerular vascular elements. This tubuloglomerular feedback mechanism plays an important role in regulating glomerular filtration rate and blood flow. Macula densa cells detect changes in luminal sodium chloride concentration through a complex series of ion transport-related intracellular events. NaCl entry via a Na:K:2Cl cotransporter and Cl exit through a basolateral channel lead to cell depolarization and increases in cytosolic calcium. Na/H exchange (NHE2) results in cell alkalization, whereas intracellular [Na] is regulated by an apically located H(Na)-K ATPase and not by the traditional basolateral Na:K ATPase. Communication from macula densa cells to the glomerular vascular elements involves ATP release across the macula densa basolateral membrane through a maxi-anion channel. The adaptation of multi-photon microscopy is providing new insights into macula densa-glomerular signaling.
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    URL: http://dx.doi.org/10.1146/annurev.physiol.65.050102.085730
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    TERMINAL DIFFERENTIATION OF INTERCALATED CELLS: The Role of Hensin (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 567-583 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract During the response to metabolic acidosis, the intercalated cell of the collecting tubule converts from one that secretes HCO3- to one that absorbs HCO3- by H+ secretion. The molecular basis of this complex change in phenotype was studied in an immortalized intercalated cell line. We found that it was induced by secretion, polymerization, and deposition of a protein, which we termed hensin, into the extracellular matrix. Surprisingly, this change in phenotype is identical to terminal differentiation of epithelial cells in that it recapitulated all the characteristics of terminal differentiation, including a change in cell shape, acquisition of specialized apical structures (microvilli and ruffles), and the ability to secrete and endocytose materials in a regulated manner from the apical membrane. Hensin is expressed in most epithelia, and others have discovered that it is deleted in a large number of epithelial tumors. These results suggest that conversion of polarity of the intercalated cells represents a process of terminal differentiation.
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    ALVEOLAR TYPE I CELLS: Molecular Phenotype and Development (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 669-695 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract Understanding of the functions and regulation of the phenotype of the alveolar type I epithelial cell has lagged behind studies of its neighbor the type II cell because of lack of cell-specific molecular markers. The recent identification of several proteins expressed by type I cells indicates that these cells may play important roles in regulation of cell proliferation, ion transport and water flow, metabolism of peptides, modulation of macrophage functions, and signaling events in the peripheral lung. Cell systems and reagents are available to characterize type I cell biology in detail, an important goal given that the cells provide the extensive surface that facilitates gas exchange in the intact animal.
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    URL: http://dx.doi.org/10.1146/annurev.physiol.65.092101.142446
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    STRUCTURE AND MECHANISM OF Na,K-ATPASE: Functional Sites and Their Interactions (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 817-849 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract The cell membrane Na,K-ATPase is a member of the P-type family of active cation transport proteins. Recently the molecular structure of the related sarcoplasmic reticulum Ca-ATPase in an E1 conformation has been determined at 2.6 A resolution. Furthermore, theoretical models of the Ca-ATPase in E2 conformations are available. As a result of these developments, these structural data have allowed construction of homology models that address the central questions of mechanism of active cation transport by all P-type cation pumps. This review relates recent evidence on functional sites of Na,K-ATPase for the substrate (ATP), the essential cofactor (Mg2+ ions), and the transported cations (Na+ and K+) to the molecular structure. The essential elements of the Ca-ATPase structure, including 10 transmembrane helices and well-defined N, P, and A cytoplasmic domains, are common to all PII-type pumps such as Na,K-ATPase and H,K-ATPases. However, for Na,K-ATPase and H,K-ATPase, which consist of both alpha- and beta-subunits, there may be some detailed differences in regions of subunit interactions. Mutagenesis, proteolytic cleavage, and transition metal-catalyzed oxidative cleavages are providing much evidence about residues involved in binding of Na+, K+, ATP, and Mg2+ ions and changes accompanying E1-E2 or E1-P-E2-P conformational transitions. We discuss this evidence in relation to N, P, and A cytoplasmic domain interactions, and long-range interactions between the active site and the Na+ and K+ sites in the transmembrane segments, for the different steps of the catalytic cycle.
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    RESOURCE WARS: The Anthropology of Mining (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Anthropology 32 (2003), S. 287-313 
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    ISSN: 0084-6570
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Ethnic Sciences , Biology
    Notes: The scope for an anthropology of mining has been dramatically transformed since the review by Ricardo Godoy, published in this review journal in 1985. The minerals boom of the 1980s led to an aggressive expansion of mine development in greenfield areas, many of them the domains of indigenous communities. Under considerable pressure, the conventional binary contest between states and corporations over the benefits and impacts of mining has been widened to incorporate the representations of local communities, and broad but unstable mining communities now coalesce around individual projects. Focused primarily on projects in developing nations of the Asia-Pacific region, this review questions the often-monolithic characterizations of state, corporate, and community forms of agency and charts the debate among anthropologists involved in mining, variously as consultants, researchers, and advocates, about appropriate terms for their engagement.
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    URL: http://dx.doi.org/10.1146/annurev.anthro.32.061002.093116
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    GENDER AND INEQUALITY IN THE GLOBAL LABOR FORCE (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Anthropology 32 (2003), S. 41-62 
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    ISSN: 0084-6570
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Ethnic Sciences , Biology
    Notes: This review examines the convergence of recent anthropological interests in gender, labor, and globalization. Attention to gender and gender inequality offers a productive strategy for the analysis of globalizing processes and their local variations and contestations. Contemporary ethnographic research explores multiple dimensions of labor and gender inequalities in the global economy: gendered patterns of labor recruitment and discipline, the transnational mobility and commodification of reproductive labor, and the gendered effects of international structural adjustment programs, among others. New and continuing research explores the diverse meanings and practices that produce a gendered global labor force, incorporating the perspectives of men and women, masculinities and femininities, and examines how these processes of gender and labor inequality articulate with other structures of subordination (such as ethnicity and nationality) to shape lived experiences of work and livelihood, exploitation and struggle, around the world.
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    URBANIZATION AND THE GLOBAL PERSPECTIVE (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Anthropology 32 (2003), S. 263-285 
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    ISSN: 0084-6570
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Ethnic Sciences , Biology
    Notes: Much of the literature about globalization exaggerates the degree of novelty. In this review, we concentrate on claims about what has changed about cities under late capitalism and globalization. Although we suggest that cities have long been influenced by global forces, we conclude that the roles of cities in the global system have changed considerably as a result of the time-space compression made possible by new transportation, communication, and organizational technologies. After discussing what the global perspective means within anthropology, and how it affects urban anthropological research, our review concentrates on three complex issues. First is whether the global factory and increasing knowledge-intensivity have decreased or increased the utility of the intermediary or brokerage roles that cities play. Second, we examine changes in how people live in globalizing cities. Third, we consider the implications of the construction and maintenance of relationships across borders for processes of citizenship, affiliation, and transnational social movements.
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    BRAIN REPRESENTATION OF OBJECT-CENTERED SPACE IN MONKEYS AND HUMANS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Neuroscience 26 (2003), S. 331-354 
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    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Visuospatial cognition requires taking into account where things are relative to each other and not just relative to the viewer. Consequently it would make sense for the brain to form an explicit representation of object-centered and not just of ego-centered space. Evidence bearing on the presence and nature of neural maps of object-centered space has come from two sources: single-neuron recording in behaving monkeys and assessment of the visual abilities of human patients with hemispatial neglect. Studies of the supplementary eye field of the monkey have revealed that it contains neurons with object-centered spatial selectivity. These neurons fire when the monkey has selected, as target for an eye movement or attention, a particular location defined relative to a reference object. Studies of neglect have revealed that in some patients the condition is expressed with respect to an object-centered and object-aligned reference frame. These patients neglect one side of an object, as defined relative to its intrinsic midline, regardless of its location and orientation relative to the viewer. The two sets of observations are complementary in the sense that the loss of neurons, such as observed in the monkey, could explain the spatial distribution of neglect in these patients.
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    CONTROL OF APOPTOSIS IN THE IMMUNE SYSTEM: Bcl-2, BH3-Only Proteins and More (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 21 (2003), S. 71-105 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Apoptotic cell death plays a critical role in the development and functioning of the immune system. During differentiation, apoptosis weeds out lymphocytes lacking useful antigen receptors and those expressing dangerous ones. Lymphocyte death is also involved in limiting the magnitude and duration of immune responses to infection. In this review, we describe the role of the Bcl-2 protein family, and to a lesser extent that of death receptors (members of the tumor necrosis factor receptor family with a death domain), in the control of lymphoid and myeloid cell survival. We also consider the pathogenic consequences of failure of apoptosis in the immune system.
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    CD8 T CELL RESPONSES TO INFECTIOUS PATHOGENS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 21 (2003), S. 29-70 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract CD8 T cells respond to viral infections but also participate in defense against bacterial and protozoal infections. In the last few years, as new methods to accurately quantify and characterize pathogen-specific CD8 T cells have become available, our understanding of in vivo T cell responses has increased dramatically. Pathogen-specific T cells, once thought to be quite rare following infection, are now known to be present at very high frequencies, particularly in peripheral, nonlymphoid tissues. With the ability to visualize in vivo CD8 T cell responses has come the recognition that T cell expansion is programmed and, to a great extent, independent of antigen concentrations. Comparison of CD8 T cell responses to different pathogens also highlights the intricate relationship between microbially induced innate inflammatory responses and the kinetics, magnitude, and character of long-term T cell responses. This review describes recent progress in some of the major murine models of CD8 T cell-mediated immunity to viral, bacterial, and protozoal infection.
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    URL: http://dx.doi.org/10.1146/annurev.immunol.21.120601.141114
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    THE MEANDERING 45-YEAR ODYSSEY OF A CLINICAL IMMUNOLOGIST* (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 21 (2003), S. 1-27 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract My work on basic and clinical immunology has focused on the regulation of the human immune response and how its dysregulation can lead to immunodeficiency, autoimmune, and malignant disorders. The early focus in our laboratory was on pathogenic mechanisms underlying hypogammaglobulinemia. Our demonstration of active suppression by human suppressor T cells changed thinking about the pathogenesis of certain immunodeficiency disorders. Recently we have focused on the cytokines interleukin-2 (IL-2) and IL-15, which have competitive functions in adaptive immune responses. IL-2 is necessary to destroy self-reactive lymphocytes and thus favors peripheral tolerance to self-antigens, whereas IL-15 favors the persistence of lymphocytes involved in the memory and effector responses to invading pathogens but risks the development of inflammatory autoimmune diseases. Our murine anti-Tac monoclonal antibody exploits these differences, as does a humanized form (daclizumab) now approved for the prevention of renal allograft rejection. New forms of therapy directed at IL-2 and IL-15 receptors may be effective against certain neoplastic diseases and autoimmune disorders and in the prevention of allograft rejection.
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    THE BIOLOGY OF IGE AND THE BASIS OF ALLERGIC DISEASE (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 21 (2003), S. 579-628 
    Details
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Allergic individuals exposed to minute quantities of allergen experience an immediate response. Immediate hypersensitivity reflects the permanent sensitization of mucosal mast cells by allergen-specific IgE antibodies bound to their high-affinity receptors (FcepsilonRI). A combination of factors contributes to such long-lasting sensitization of the mast cells. They include the homing of mast cells to mucosal tissues, the local synthesis of IgE, the induction of FcepsilonRI expression on mast cells by IgE, the consequent downregulation of FcgammaR (through an insufficiency of the common gamma-chains), and the exceptionally slow dissociation of IgE from FcepsilonRI. To understand the mechanism of the immediate hypersensitivity phenomenon, we need explanations of why IgE antibodies are synthesized in preference to IgG in mucosal tissues and why the IgE is so tenaciously retained on mast cell-surface receptors. There is now compelling evidence that the microenvironment of mucosal tissues of allergic disease favors class switching to IgE; and the exceptionally high affinity of IgE for FcepsilonRI can now be interpreted in terms of the recently determined crystal structures of IgE-FcepsilonRI and IgG-FcgammaR complexes. The rate of local IgE synthesis can easily compensate for the rate of the antibody dissociation from its receptors on mucosal mast cells. Effective mechanisms ensure that allergic reactions are confined to mucosal tissues, thereby minimizing the risk of systemic anaphylaxis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.immunol.21.120601.141103
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    BIOLOGY OF HEMATOPOIETIC STEM CELLS AND PROGENITORS: Implications for Clinical Application (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 21 (2003), S. 759-806 
    Details
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Stem cell biology is scientifically, clinically, and politically a current topic. The hematopoietic stem cell, the common ancestor of all types of blood cells, is one of the best-characterized stem cells in the body and the only stem cell that is clinically applied in the treatment of diseases such as breast cancer, leukemias, and congenital immunodeficiencies. Multicolor cell sorting enables the purification not only of hematopoietic stem cells, but also of their downstream progenitors such as common lymphoid progenitors and common myeloid progenitors. Recent genetic approaches including gene chip technology have been used to elucidate the gene expression profile of hematopoietic stem cells and other progenitors. Although the mechanisms that control self-renewal and lineage commitment of hematopoietic stem cells are still ambiguous, recent rapid advances in understanding the biological nature of hematopoietic stem and progenitor cells have broadened the potential application of these cells in the treatment of diseases.
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    URL: http://dx.doi.org/10.1146/annurev.immunol.21.120601.141007
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    T CELL DYNAMICS IN HIV-1 INFECTION* (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 21 (2003), S. 265-304 
    Details
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract In the absence of antiretroviral treatment, HIV-1 establishes a chronic, progressive infection of the human immune system that invariably, over the course of years, leads to its destruction and fatal immunodeficiency. Paradoxically, while viral replication is extensive throughout the course of infection, deterioration of conventional measures of immunity is slow, including the characteristic loss of CD4+ T cells that is thought to play a key role in the development of immunodeficiency. This conundrum suggests that CD4+ T cell-directed viral cytopathicity alone cannot explain the course of disease. Indeed, recent advances now indicate that HIV-1 pathogenesis is likely to result from a complex interplay between the virus and the immune system, particularly the mechanisms responsible for T cell homeostasis and regeneration. We review these data and present a model of HIV-1 pathogenesis in which the protracted loss of CD4+ T cells results from early viral destruction of selected memory T cell populations, followed by a combination of profound increases in overall memory T cell turnover, damage to the thymus and other lymphoid tissues, and physiological limitations in peripheral CD4+ T cell renewal.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.immunol.21.120601.141053
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    IL-13 EFFECTOR FUNCTIONS* (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 21 (2003), S. 425-456 
    Details
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract IL-13 was first recognized for its effects on B cells and monocytes, where it upregulated class II expression, promoted IgE class switching and inhibited inflammatory cytokine production. It was also thought to be functionally redundant with IL-4. However, studies conducted with knockout mice, neutralizing antibodies, and novel antagonists demonstrate that IL-13 possesses several unique effector functions that distinguish it from IL-4. Resistance to most gastrointestinal nematodes is mediated by type-2 cytokine responses, in which IL-13 plays a dominant role. By regulating cell-mediated immunity, IL-13 modulates resistance to intracellular organisms including Leishmania major, Leishmania mexicana, and Listeria monocytogenes. In the lung, IL-13 is the central mediator of allergic asthma, where it regulates eosinophilic inflammation, mucus secretion, and airway hyperresponsiveness. Manipulation of IL-13 effector function may also prove useful in the treatment of some cancers like B-cell chronic lymphocytic leukemia and Hodgkin's disease, where IL-13 modulates apoptosis or tumor cell growth. IL-13 can also inhibit tumor immunosurveillance. As such, inhibitors of IL-13 might be effective as cancer immunotherapeutics by boosting type-1-associated anti-tumor defenses. Finally, IL-13 was revealed as a potent mediator of tissue fibrosis in both schistosomiasis and asthma, which indicates that it is a key regulator of the extracellular matrix. The mechanisms that regulate IL-13 production and/or function have also been investigated, and IL-4, IL-12, IL-18, IFN-gamma, IL-10, TGF-beta, TNF-alpha, and the IL-4/IL-13 receptor complex play important roles. This review highlights the effector functions of IL-13 and describes multiple pathways for modulating its activity in vivo.
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    URL: http://dx.doi.org/10.1146/annurev.immunol.21.120601.141142
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    COLLECTINS AND FICOLINS: Humoral Lectins of the Innate Immune Defense (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 21 (2003), S. 547-578 
    Details
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Collectins and ficolins, present in plasma and on mucosal surfaces, are humoral molecules of the innate immune systems, which recognize pathogen-associated molecular patterns. The human collectins, mannan-binding lectin (MBL) and surfactant protein A and D (SP-A and SP-D), are oligomeric proteins composed of carbohydrate-recognition domains (CRDs) attached to collagenous regions and are thus structurally similar to the ficolins, L-ficolin, M-ficolin, and H-ficolin. However, they make use of different CRD structures: C-type lectin domains for the collectins and fibrinogen-like domains for the ficolins. Upon recognition of the infectious agent, MBL and the ficolins initiate the lectin pathway of complement activation through attached serine proteases (MASPs), whereas SP-A and SP-D rely on other effector mechanisms: direct opsonization, neutralization, and agglutination. This limits the infection and concurrently orchestrates the subsequent adaptive immune response. Deficiencies of the proteins may predispose to infections or other complications, e.g., reperfusion injuries or autoimmune diseases. Structure, function, clinical implications, and phylogeny are reviewed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.immunol.21.120601.140954
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    TOLEROGENIC DENDRITIC CELLS* (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 21 (2003), S. 685-711 
    Details
    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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    URL: http://dx.doi.org/10.1146/annurev.immunol.21.120601.141040
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    B CELL CHRONIC LYMPHOCYTIC LEUKEMIA: Lessons Learned from Studies of the B Cell Antigen Receptor (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 21 (2003), S. 841-894 
    Details
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract B cell chronic lymphocytic leukemia (B-CLL) is an accumulative disease of slowly proliferating CD5+ B lymphocytes that develops in the aging population. Whereas some patients with B-CLL have an indolent course and die after many years from unrelated causes, others progress very rapidly and succumb within a few years from this currently incurable leukemia. Over the past decade studies of the structure and function of the B cell antigen receptor (BCR) used by these leukemic cells have helped redefine the nature of this disease. In this review we summarize and reinterpret several aspects of these BCR-related studies and how they might relate to the disease. In particular, we address the ability of antigens to select out and drive B cell clones from the normal state to overt leukemic cells by binding to BCRs that are relatively unique and characteristic of B-CLL cells. The differential capacity of some B-CLL cases to continue to transduce signals through the BCR during the leukemic phase and the consequences for the in vivo biology of the leukemic clone is also considered. Finally, we discuss current and emerging views of the cellular origin of B-CLL cells and the differentiation pathways down which we believe these cells progress.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.immunol.21.120601.141018
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    BIOSYNTHESIS AND METABOLISM OF BRASSINOSTEROIDS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Plant Physiology and Plant Molecular Biology 54 (2003), S. 137-164 
    Details
    ISSN: 1040-2519
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Brassinosteroids (BRs) are steroid hormones that regulate the growth and development of plants. Detailed study of the biosynthesis of brassinolide, a C28 BR, revealed that two parallel routes, the early and late C-6 oxidation pathways, are connected at multiple steps and also are linked to the early C-22 oxidation pathway. Thus, BR biosynthetic pathways are highly networked. Furthermore, the biosynthesis of C27 BRs was shown to proceed in a similar way to that of C28 BRs. Information on enzymes and genes involved in the BR biosynthesis, as well as their regulation, has been obtained using BR-deficient and BR-insensitive mutants. In addition, the biosynthesis of sterols, which were recently recognized not only as precursors of BRs and membrane constituents, but also as modulators of plant development, is discussed. Various metabolic reactions of BRs including epimerization, oxidation, and conjugation are also summarized.
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    URL: http://dx.doi.org/10.1146/annurev.arplant.54.031902.134921
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    STRUCTURE OF LINKAGE DISEQUILIBRIUM IN PLANTS* (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Plant Physiology and Plant Molecular Biology 54 (2003), S. 357-374 
    Details
    ISSN: 1040-2519
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Future advances in plant genomics will make it possible to scan a genome for polymorphisms associated with qualitative and quantitative traits. Before this potential can be realized, we must understand the nature of linkage disequilibrium (LD) within a genome. LD, the nonrandom association of alleles at different loci, plays an integral role in association mapping, and determines the resolution of an association study. Recently, association mapping has been exploited to dissect quantitative trait loci (QTL). With the exception of maize and Arabidopsis, little research has been conducted on LD in plants. The mating system of the species (selfing versus outcrossing), and phenomena such as population structure and recombination hot spots, can strongly influence patterns of LD. The basic patterns of LD in plants will be better understood as more species are analyzed.
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    URL: http://dx.doi.org/10.1146/annurev.arplant.54.031902.134907
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    TRANSFER CELLS: Cells Specialized for a Special Purpose (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Plant Physiology and Plant Molecular Biology 54 (2003), S. 431-454 
    Details
    ISSN: 1040-2519
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Transfer cells are plant cells with secondary wall ingrowths. These cells are ubiquitous, occurring in all plant taxonomic groups and in algae and fungi. Transfer cells form from differentiated cells across developmental windows and in response to stress. They are considered to play a central role in nutrient distribution by facilitating high rates of transport at bottlenecks for apo-/symplasmic solute exchange. These properties are conferred by their unique structural features-an invaginated secondary wall ensheathed by an amplified area of plasma membrane enriched in a suite of solute transporters. Recent development of transfer cell experimental systems, combined with technologies to image the three-dimensional structure of wall ingrowths, is allowing identification of inductive and regulatory signals, discovery of sequential processes involved in their differentiation, and a search for transfer cell identity genes. A model of key events in differentiation of a transfer cell is presented to highlight areas for future investigation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.arplant.54.031902.134812
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    CONJECTURES, REFUTATIONS, AND EXTRAPOLATIONS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Plant Physiology and Plant Molecular Biology 54 (2003), S. 1-21 
    Details
    ISSN: 1040-2519
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.arplant.54.031902.134957
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    SINGLE-NUCLEOTIDE MUTATIONS FOR PLANT FUNCTIONAL GENOMICS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Plant Physiology and Plant Molecular Biology 54 (2003), S. 375-401 
    Details
    ISSN: 1040-2519
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract In the present genomics era, powerful reverse-genetic strategies are needed to elucidate gene and protein function in the context of a whole organism. However, most current techniques lack the generality and high-throughput potential of descriptive genomic approaches, such as those that rely on microarray hybridization. For example, in plant research, effective insertional mutagenesis and transgenic methods are limited to relatively few species or are inefficient. Fortunately, single-nucleotide changes can be induced in any plant by using traditional chemical mutagens, and progress has been made in efficiently detecting changes. Because base substitutions in proteins provide allelic series, and not just knockouts, this strategy can yield refined insights into protein function. Here, we review recent progress that has been made in genome-wide screening for point mutations and natural variation in plants. Its general applicability leads to the expectation that traditional mutagenesis followed by high-throughput detection will become increasingly important for plant functional genomics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.arplant.54.031902.135009
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    LIGNIN BIOSYNTHESIS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Plant Physiology and Plant Molecular Biology 54 (2003), S. 519-546 
    Details
    ISSN: 1040-2519
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract The lignin biosynthetic pathway has been studied for more than a century but has undergone major revisions over the past decade. Significant progress has been made in cloning new genes by genetic and combined bioinformatics and biochemistry approaches. In vitro enzymatic assays and detailed analyses of mutants and transgenic plants altered in the expression of lignin biosynthesis genes have provided a solid basis for redrawing the monolignol biosynthetic pathway, and structural analyses have shown that plant cell walls can tolerate large variations in lignin content and structure. In some cases, the potential value for agriculture of transgenic plants with modified lignin structure has been demonstrated. This review presents a current picture of monolignol biosynthesis, polymerization, and lignin structure.
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    URL: http://dx.doi.org/10.1146/annurev.arplant.54.031902.134938
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    MEMBRANE-BOUND DIIRON CARBOXYLATE PROTEINS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Plant Physiology and Plant Molecular Biology 54 (2003), S. 497-517 
    Details
    ISSN: 1040-2519
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Four proteins have been identified recently as diiron carboxylate proteins on the basis of conservation of six amino acids (four carboxylate residues and two histidines) constituting an iron-binding motif. Unlike previously identified proteins with this motif, biochemical studies indicate that each of these proteins is membrane bound, although homology modeling rules out a transmembrane mode of binding. Therefore, the predicted structure of each protein [the alternative oxidase (AOX), the plastid terminal oxidase (PTOX), the diiron 5-demethoxyquinone hydroxylase (DMQ hydroxylase), and the aerobic Mg-protoporphyrin IX monomethylester hydroxylase (MME hydroxylase)] is that of a protein bound monotopically to one leaflet of the membrane bilayer. Three of these enzymes utilize a quinol substrate, with two oxidizing the quinol (AOX and PTOX) and one hydroxylating it (DMQ hydroxylase). MME hydroxylase is involved in synthesis of the isocyclic ring of chlorophyll. Two enzymes are involved in respiration (AOX and, indirectly, the diiron DMQ hydroxylase through ubiquinone biosynthesis) and two in photosynthesis, through their roles in carotenoid and chlorophyll biosynthesis (PTOX and MME hydroxylase, respectively). We discuss what is known about each enzyme as well as our expectations based on their identification as interfacially bound proteins with a diiron carboxylate active site.
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    URL: http://dx.doi.org/10.1146/annurev.arplant.54.031902.134915
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    FUNCTIONAL GENOMICS OF P450S (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Plant Physiology and Plant Molecular Biology 54 (2003), S. 629-667 
    Details
    ISSN: 1040-2519
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Plant systems utilize a diverse array of cytochrome P450 monooxygenases (P450s) in their biosynthetic and detoxicative pathways. Those P450s in biosynthetic pathways play critical roles in the synthesis of lignins, UV protectants, pigments, defense compounds, fatty acids, hormones, and signaling molecules. Those in catabolic pathways participate in the breakdown of endogenous compounds and toxic compounds encountered in the environment. Because of their roles in this wide diversity of metabolic processes, plant P450 proteins and transcripts can serve as downstream reporters for many different biochemical pathways responding to chemical, developmental, and environmental cues. This review focuses initially on defining P450 biochemistries, nomenclature systems, and the relationships between genes in the extended P450 superfamily that exists in all plant species. Subsequently, it focuses on outlining the many approaches being used to assign function to individual P450 proteins and gene loci. The examples of assigned P450 activities that are spread throughout this review highlight the importance of understanding and utilizing P450 sequences as markers for linking biochemical pathway responses to physiological processes.
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    URL: http://dx.doi.org/10.1146/annurev.arplant.54.031902.134840
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    THE DROSOPHILA MELANOGASTER GENOME (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genomics and Human Genetics 4 (2003), S. 89-117 
    Details
    ISSN: 1527-8204
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Drosophila's importance as a model organism made it an obvious choice to be among the first genomes sequenced, and the Release 1 sequence of the euchromatic portion of the genome was published in March 2000. This accomplishment demonstrated that a whole genome shotgun (WGS) strategy could produce a reliable metazoan genome sequence. Despite the attention to sequencing methods, the nucleotide sequence is just the starting point for genome-wide analyses; at a minimum, the genome sequence must be interpreted using expressed sequence tag (EST) and complementary DNA (cDNA) evidence and computational tools to identify genes and predict the structures of their RNA and protein products. The functions of these products and the manner in which their expression and activities are controlled must then be assessed-a much more challenging task with no clear endpoint that requires a wide variety of experimental and computational methods. We first review the current state of the Drosophila melanogaster genome sequence and its structural annotation and then briefly summarize some promising approaches that are being taken to achieve an initial functional annotation.
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    URL: http://dx.doi.org/10.1146/annurev.genom.4.070802.110323
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    PEROXISOME BIOGENESIS DISORDERS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genomics and Human Genetics 4 (2003), S. 165-211 
    Details
    ISSN: 1527-8204
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: The peroxisome biogenesis disorders (PBDs) comprise 12 autosomal recessive complementation groups (CGs). The multisystem clinical phenotype varies widely in severity and results from disturbances in both development and metabolic homeostasis. Progress over the last several years has lead to identification of the genes responsible for all of these disorders and to a much improved understanding of the biogenesis and function of the peroxisome. Increasing availability of mouse models for these disorders offers hope for a better understanding of their pathophysiology and for development of therapies that might especially benefit patients at the milder end of the clinical phenotype.
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    URL: http://dx.doi.org/10.1146/annurev.genom.4.070802.110424
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    NONSYNDROMIC SEIZURE DISORDERS: Epilepsy and the Use of the Internet to Advance Research (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Genomics and Human Genetics 4 (2003), S. 437-457 
    Details
    ISSN: 1527-8204
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: The progress in understanding the genetics of nonsyndromic epilepsy is the direct result of dramatic advances made by the Human Genome Project. The development of thousands of precisely mapped genetic markers and the nearly complete sequencing of the entire human genome in 2001 allowed genetic researchers in epilepsy to identify many loci and genes as causal in inherited idiopathic epilepsy. This substantial increase in information has required the development of accurate and online bioinformatic databases. Only the Internet can enable such large amounts of precise DNA sequence information to be transferred to researchers. Along with the construction of these databases has been the development of efficient search algorithms for specific DNA sequences and genetic information. This article summarizes the effect that this burst of new genomic information has had on research aimed at discovering the underlying genetic factors for nonsyndromic epilepsy. Many of the web sites important to epilepsy gene discovery are listed and discussed in this article, including sites with extensive information on genetic markers, genetic analysis, gene sequence, gene expression, gene mutations, and DNA sequence variation. Continued acquisition of information on naturally occurring DNA sequence variants will greatly help research directed towards understanding the genetic susceptibility of the common, nonsyndromic epilepsies and will lead to the promise of personalized medicine.
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    URL: http://dx.doi.org/10.1146/annurev.genom.4.071902.102155
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