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  • Articles  (2,533)
  • American Association for the Advancement of Science (AAAS)  (2,354)
  • Annual Reviews  (179)
  • Copernicus
  • 2020-2024
  • 2005-2009  (2,533)
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  • 1980-1984
  • 2006  (2,533)
  • Medicine  (2,533)
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  • 2020-2024
  • 2005-2009  (2,533)
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  • 1
    Electronic Resource
    Electronic Resource
    ROLE OF FXYD PROTEINS IN ION TRANSPORT (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 431-459 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: The FXYD proteins are a family of seven homologous single transmembrane segment proteins (FXYD1Đ??7), expressed in a tissue-specific fashion. The FXYD proteins modulate the function of Na,K-ATPase, thus adapting kinetic properties of active Na+ and K+ transport to the specific needs of different cells. Six FXYD proteins ( 1Đ??5, 7 ) are known to interact with Na,K-ATPase and affect its kinetic properties in specific ways. Although effects of FXYD proteins on parameters such as K1/2Na+, K1/2K+, KmATP, and Vmax are modest, usually twofold, these effects may have important long-term consequences for homeostasis of cation balance. In this review we summarize basic features of FXYD proteins and present recent evidence for functional effects, structure-function relations and structural interactions with Na,K-ATPase. We then discuss possible physiological roles, based on in vitro observations and newly available knockout mice models. Finally, we also consider evidence that FXYD proteins affect functioning of other ion transport systems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.68.040104.131852
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  • 2
    Electronic Resource
    Electronic Resource
    ENDOTHELIAL-CARDIOMYOCYTE INTERACTIONS IN CARDIAC DEVELOPMENT AND REPAIR (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 51-66 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Communication between endothelial cells and cardiomyocytes regulates not only early cardiac development but also adult cardiomyocyte function, including the contractile state. In the normal mammalian myocardium, each cardiomyocyte is surrounded by an intricate network of capillaries and is next to endothelial cells. Cardiomyocytes depend on endothelial cells not only for oxygenated blood supply but also for local protective signals that promote cardiomyocyte organization and survival. While endothelial cells direct cardiomyocytes, cardiomyocytes reciprocally secrete factors that impact endothelial cell function. Understanding how endothelial cells communicate with cardiomyocytes will be critical for cardiac regeneration, in which the ultimate goal is not simply to improve systolic function transiently but to establish new myocardium that is both structurally and functionally normal in the long term.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.68.040104.124629
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  • 3
    Electronic Resource
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    PERMEATION AND SELECTIVITY OF TRP CHANNELS (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 685-717 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Ion channels are pore-forming transmembrane proteins that allow ions to permeate biological membranes. Pore structure plays a crucial role in determining the ion permeation and selectivity properties of particular channels. In the past few decades, efforts have been undertaken to identify key elements of the pore regions of different classes of ion channels. In this review, we summarize current knowledge about permeation and selectivity of channel proteins from the transient receptor potential (TRP) superfamily. Whereas all TRP channels are permeable for cations, only two TRP channels are impermeable for Ca2+ (TRPM4, TRPM5), and two others are highly Ca2+ permeable (TRPV5, TRPV6). Despite the great advances in the TRP channel field during the past decade, only a limited number of reports have dealt with functional characterization of pore properties, biophysical aspects of cation permeation, or description of pore structures of TRP channels. This review gives an overview of available experimental and theoretical data and discusses the functional impact of pore-structure modifications on TRP channel properties.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.68.040204.101406
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  • 4
    Electronic Resource
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    PROTECTING THE PUMP: Controlling Myocardial Inflammatory Responses (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 67-95 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Because of the anatomy, function, and nonregenerative nature of the myocardium, inflammation in this tissue is not well tolerated. Nevertheless, various diseases of the heart are characterized by inflammatory responses involving the effector mechanisms of innate and adaptive (lymphocyte-dependent) immunity. The innate immune response to ischemia-reperfusion injury is, by far, the most common cause of myocardial inflammation. Innate responses may have beneficial influences that preserve myocardial function in the short term but may be maladaptive in chronic states. Adaptive responses in the myocardium occur with infection or loss of tolerance, and lead to myocarditis. Given the narrow margin for benefit of cardiac inflammation, special regulatory mechanisms likely raise the threshold, compared to other tissues, for the induction and persistence of adaptive immune responses. These mechanisms include strong central and peripheral T cell tolerance to heart antigens and induction of anti-inflammatory feedback mechanisms involving cytokines such as interferon-??.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.68.040104.124611
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  • 5
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    LXRS AND FXR: The Yin and Yang of Cholesterol and Fat Metabolism (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 159-191 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Liver X receptors (LXRs) and farnesoid X receptor (FXR) are nuclear receptors that function as intracellular sensors for sterols and bile acids, respectively. In response to their ligands, these receptors induce transcriptional responses that maintain a balanced, finely tuned regulation of cholesterol and bile acid metabolism. LXRs also permit the efficient storage of carbohydrate- and fat-derived energy, whereas FXR activation results in an overall decrease in triglyceride levels and modulation of glucose metabolism. The elegant, dual interplay between these two receptor systems suggests that they coevolved to constitute a highly sensitive and efficient system for the maintenance of total body fat and cholesterol homeostasis. Emerging evidence suggests that the tissue-specific action of these receptors is also crucial for the proper function of the cardiovascular, immune, reproductive, endocrine pancreas, renal, and central nervous systems. Together, LXRs and FXR represent potential therapeutic targets for the treatment and prevention of numerous metabolic and lipid-related diseases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.68.033104.152158
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  • 6
    Electronic Resource
    Electronic Resource
    BRAINSTEM CIRCUITS REGULATING GASTRIC FUNCTION (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 279-305 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Brainstem parasympathetic circuits that modulate digestive functions of the stomach are comprised of afferent vagal fibers, neurons of the nucleus tractus solitarius (NTS), and the efferent fibers originating in the dorsal motor nucleus of the vagus (DMV). A large body of evidence has shown that neuronal communications between the NTS and the DMV are plastic and are regulated by the presence of a variety of neurotransmitters and circulating hormones as well as the presence, or absence, of afferent input to the NTS. These data suggest that descending central nervous system inputs as well as hormonal and afferent feedback resulting from the digestive process can powerfully regulate vago-vagal reflex sensitivity. This paper first reviews the essential "static" organization and function of vago-vagal gastric control neurocircuitry. We then present data on the opioidergic modulation of NTS connections with the DMV as an example of the "gating" of these reflexes, i.e., how neurotransmitters, hormones, and vagal afferent traffic can make an otherwise static autonomic reflex highly plastic.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.68.040504.094635
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  • 7
    Electronic Resource
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    SGK KINASES AND THEIR ROLE IN EPITHELIAL TRANSPORT (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 461-490 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: The serum/glucocorticoid-induced kinase Sgk1 plays an important role in the regulation of epithelial ion transport. This kinase is very rapidly regulated at the transcriptional level as well as via posttranslational modifications involving phosphorylation by the MAP or PI-3 kinase pathways and/or ubiquitylation. Although Sgk1 is a cell survival kinase, its primary role likely concerns the regulation of epithelial ion transport, as suggested by the phenotype of Sgk1-null mice, which display a defect in Na+ homeostasis owing to disturbed renal tubular Na+ handling. In this review we first discuss the molecular, cellular, and regulatory aspects of Sgk1 and its paralogs. We then discuss its roles in the physiology and pathophysiology of epithelial ion transport.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.68.040104.131654
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  • 8
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    DESIGN AND FUNCTION OF SUPERFAST MUSCLES: New Insights into the Physiology of Skeletal Muscle (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 193-221 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Superfast muscles of vertebrates power sound production. The fastest, the swimbladder muscle of toadfish, generates mechanical power at frequencies in excess of 200 Hz. To operate at these frequencies, the speed of relaxation has had to increase approximately 50-fold. This increase is accomplished by modifications of three kinetic traits: (a) a fast calcium transient due to extremely high concentration of sarcoplasmic reticulum (SR)-Ca2+ pumps and parvalbumin, (b) fast off-rate of Ca2+ from troponin C due to an alteration in troponin, and (c) fast cross-bridge detachment rate constant (g, 50 times faster than that in rabbit fast-twitch muscle) due to an alteration in myosin. Although these three modifications permit swimbladder muscle to generate mechanical work at high frequencies (where locomotor muscles cannot), it comes with a cost: The high g causes a large reduction in attached force-generating cross-bridges, making the swimbladder incapable of powering low-frequency locomotory movements. Hence the locomotory and sound-producing muscles have mutually exclusive designs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.68.040104.105418
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  • 9
    Electronic Resource
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    CLAUDINS AND EPITHELIAL PARACELLULAR TRANSPORT (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 403-429 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Tight junctions form continuous intercellular contacts controlling solute movement through the paracellular pathway across epithelia. Paracellular barriers vary among epithelia in electrical resistance and behave as if they are lined with pores that have charge and size selectivity. Recent evidence shows that claudins, a large family (at least 24 members) of intercellular adhesion molecules, form the seal and its variable pore-like properties. This evidence comes from the study of claudins expressed in cultured epithelial cell models, genetically altered mice, and human mutants. We review information on the structure, function, and transcriptional and posttranslational regulation of the claudin family as well as of their evolutionarily distant relatives called the PMP22/EMP/MP20/claudin, or pfam00822, superfamily.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.68.040104.131404
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  • 10
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    THE COMPARATIVE PHYSIOLOGY OF FOOD DEPRIVATION: From Feast to Famine (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 223-251 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: The ability of animals to survive food deprivation is clearly of considerable survival value. Unsurprisingly, therefore, all animals exhibit adaptive biochemical and physiological responses to the lack of food. Many animals inhabit environments in which food availability fluctuates or encounters with appropriate food items are rare and unpredictable; these species offer interesting opportunities to study physiological adaptations to fasting and starvation. When deprived of food, animals employ various behavioral, physiological, and structural responses to reduce metabolism, which prolongs the period in which energy reserves can cover metabolism. Such behavioral responses can include a reduction in spontaneous activity and a lowering in body temperature, although in later stages of food deprivation in which starvation commences, activity may increase as food-searching is activated. In most animals, the gastrointestinal tract undergoes marked atrophy when digestive processes are curtailed; this structural response and others seem particularly pronounced in species that normally feed at intermittent intervals. Such animals, however, must be able to restore digestive functions soon after feeding, and these transitions appear to occur at low metabolic costs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.68.040104.105739
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  • 11
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    REGULATION OF NORMAL AND CYSTIC FIBROSIS AIRWAY SURFACE LIQUID VOLUME BY PHASIC SHEAR STRESS (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 543-561 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: The physical removal of viruses and bacteria on the mucociliary escalator is an important aspect of the mammalian lung's innate defense mechanism. The volume of airway surface liquid (ASL) present in the respiratory tract is a critical determinant of both mucus hydration and the rate of mucus clearance from the lung. ASL volume is maintained by the predominantly ciliated epithelium via coordinated regulation of (a) absorption, by the epithelial Na+ channel, and (b) secretion, by the Ca2+ -activated Cl channel (CaCC) and CFTR. This review provides an update on our current understanding of how shear stress regulates ASL volume height in normal and cystic fibrosis (CF) airway epithelia through extracellular ATP- and adenosine (ADO)-mediated pathways that modulate ion transport and ASL volume homeostasis. We also discuss (a) how derangement of the ADO-CFTR pathway renders CF airways vulnerable to viral infections that deplete ASL volume and produce mucus stasis, and (b) potential shear stressĐ??dependent therapies for CF.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.68.072304.112754
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  • 12
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    TRP CHANNELS IN C. ELEGANS (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 719-736 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: The TRP (transient receptor potential) superfamily of cation channels is present in all eukaryotes, from yeast to mammals. Many TRP channels have been studied in the nematode Caenorhabditis elegans, revealing novel biological functions, regulatory modes, and mechanisms of localization. C. elegans TRPV channels function in olfaction, mechanosensation, osmosensation, and activity-dependent gene regulation. Their activity is regulated by G protein signaling and polyunsaturated fatty acids. C. elegans TRPPs related to human polycystic kidney disease genes are expressed in male-specific neurons. The KLP-6 kinesin directs TRPP channels to cilia, where they may interact with F0/F1 ATPases. A sperm-specific TRPC channel, TRP-3, is required for fertilization. Upon sperm activation, TRP-3 translocates from an intracellular compartment to the plasma membrane to allow store-operated Ca2+ entry. The TRPM channels GON-2 and GTL-2 regulate Mg2+ homeostasis and Mg2+ uptake by intestinal cells; GON-2 is also required for gonad development. The TRPML CUP-5 promotes normal lysosome biogenesis and prevents apoptosis. Dynamic, precise expression of TRP proteins generates a remarkable range of cellular functions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.68.040204.100715
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  • 13
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    INSIGHTS ON TRP CHANNELS FROM IN VIVO STUDIES IN DROSOPHILA (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 649-684 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Transient receptor potential (TRP) channels mediate responses in a large variety of signaling mechanisms. Most studies on mammalian TRP channels rely on heterologous expression, but their relevance to in vivo tissues is not entirely clear. In contrast, Drosophila TRP and TRP-like (TRPL) channels allow direct analyses of in vivo function. In Drosophila photoreceptors, activation of TRP and TRPL is mediated via the phosphoinositide cascade, with both Ca2+ and diacylglycerol (DAG) essential for generating the light response. In tissue culture cells, TRPL channels are constitutively active, and lipid second messengers greatly facilitate this activity. Inhibition of phospholipase C (PLC) completely blocks lipid activation of TRPL, suggesting that lipid activation is mediated via PLC. In vivo studies in mutant Drosophila also reveal an acute requirement for lipid-producing enzyme, which may regulate PLC activity. Thus, PLC and its downstream second messengers, Ca2+ and DAG, constitute critical mediators of TRP/TRPL gating in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.68.040204.100939
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  • 14
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    CARDIAC REGENERATION: Repopulating the Heart (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 29-49 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Many forms of pediatric and adult heart disease result from a deficiency in cardiomyocyte number. Through repopulation of the heart with new cardiomyocytes (that is, induction of regenerative cardiac growth), cardiac disease potentially can be reversed, provided that the newly formed myocytes structurally and functionally integrate in the preexisting myocardium. A number of approaches have been utilized to effect regenerative growth of the myocardium in experimental animals. These include interventions aimed at enhancing the ability of cardiomyocytes to proliferate in response to cardiac injury, as well as transplantation of cardiomyocytes or myogenic stem cells into diseased hearts. Here we review efforts to induce myocardial regeneration. We also provide a critical review of techniques currently used to assess cardiac regeneration and functional integration of de novo cardiomyocytes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.68.040104.124530
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  • 15
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    FROM MICE TO MEN: Insights into the Insulin Resistance Syndromes (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 123-158 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: The insulin resistance syndrome refers to a constellation of findings, including glucose intolerance, obesity, dyslipidemia, and hypertension, that promote the development of type 2 diabetes, cardiovascular disease, cancer, and other disorders. Defining the pathophysiological links between insulin resistance, the insulin resistance syndrome, and its sequelae is critical to understanding and treating these disorders. Over the past decade, two approaches have provided important insights into how changes in insulin signaling produce the spectrum of phenotypes associated with insulin resistance. First, studies using tissue-specific knockouts or tissue-specific reconstitution of the insulin receptor in vivo in mice have enabled us to deconstruct the insulin resistance syndromes by dissecting the contributions of different tissues to the insulin-resistant state. Second, in vivo and in vitro studies of the complex network of insulin signaling have provided insight into how insulin resistance can develop in some pathways whereas insulin sensitivity is maintained in others. These data, taken together, give us a framework for understanding the relationship between insulin resistance and the insulin resistance syndromes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.68.040104.124723
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  • 16
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    INTERSTITIAL CELLS OF CAJAL AS PACEMAKERS IN THE GASTROINTESTINAL TRACT (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 307-343 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: In the gastrointestinal tract, phasic contractions are caused by electrical activity termed slow waves. Slow waves are generated and actively propagated by interstitial cells of Cajal (ICC). The initiation of pacemaker activity in the ICC is caused by release of Ca2+ from inositol 1,4,5-trisphosphate (IP3) receptorĐ??operated stores, uptake of Ca2+ into mitochondria, and the development of unitary currents. Summation of unitary currents causes depolarization and activation of a dihydropyridine-resistant Ca2+ conductance that entrains pacemaker activity in a network of ICC, resulting in the active propagation of slow waves. Slow wave frequency is regulated by a variety of physiological agonists and conditions, and shifts in pacemaker dominance can occur in response to both neural and nonneural inputs. Loss of ICC in many human motility disorders suggests exciting new hypotheses for the etiology of these disorders.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.68.040504.094718
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  • 17
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    AN INTRODUCTION TO TRP CHANNELS (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 619-647 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: The aim of this review is to provide a basic framework for understanding the function of mammalian transient receptor potential (TRP) channels, particularly as they have been elucidated in heterologous expression systems. Mammalian TRP channel proteins form six-transmembrane (6-TM) cation-permeable channels that may be grouped into six subfamilies on the basis of amino acid sequence homology (TRPC, TRPV, TRPM, TRPA, TRPP, and TRPML). Selected functional properties of TRP channels from each subfamily are summarized in this review. Although a single defining characteristic of TRP channel function has not yet emerged, TRP channels may be generally described as calcium-permeable cation channels with polymodal activation properties. By integrating multiple concomitant stimuli and coupling their activity to downstream cellular signal amplification via calcium permeation and membrane depolarization, TRP channels appear well adapted to function in cellular sensation. Our review of recent literature implicating TRP channels in neuronal growth cone steering suggests that TRPs may function more widely in cellular guidance and chemotaxis. The TRP channel gene family and its nomenclature, the encoded proteins and alternatively spliced variants, and the rapidly expanding pharmacology of TRP channels are summarized in online supplemental material.
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    URL: http://dx.doi.org/10.1146/annurev.physiol.68.040204.100431
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  • 18
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    COMMENTARY ON THE PLEASURES OF SOLVING IMPOSSIBLE PROBLEMS OF EXPERIMENTAL PHYSIOLOGY (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 1-28 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: This commentary presents a series of examples of "impossible experimental problems" that we have encountered over the years in addressing various challenging questions in physiology. We aim to show how stimulating the challenges of physiology can be and demonstrate how our naive invocation of methods from disparate fields of science and engineering has led to delightful resolutions of physiological challenges that were utterly new to this intrepid interdisciplinary researcher.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.68.040504.151957
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  • 19
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    NUCLEAR AND MITOCHONDRIAL COMPARTMENTATION OF OXIDATIVE STRESS AND REDOX SIGNALING (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 46 (2006), S. 215-234 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: New methods to measure thiol oxidation show that redox compartmentation functions as a mechanism for specificity in redox signaling and oxidative stress. Redox Western analysis and redox-sensitive green fluorescent proteins provide means to quantify thiol/disulfide redox changes in specific subcellular compartments. Analyses using these techniques show that the relative redox states from most reducing to most oxidizing are mitochondria 〉 nuclei 〉 cytoplasm 〉 endoplasmic reticulum 〉 extracellular space. Mitochondrial thiols are an important target of oxidant-induced apoptosis and necrosis and are especially vulnerable to oxidation because of the relatively alkaline pH. Maintenance of a relatively reduced nuclear redox state is critical for transcription factor binding in transcriptional activation in response to oxidative stress. The new methods are applicable to a broad range of experimental systems and their use will provide improved understanding of the pharmacologic and toxicologic actions of drugs and toxicants.
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    URL: http://dx.doi.org/10.1146/annurev.pharmtox.46.120604.141122
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  • 20
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    HUMAN FLAVIN-CONTAINING MONOOXYGENASES (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 46 (2006), S. 65-100 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: This review summarizes recent information concerning the pharmacological and toxicological significance of the human flavin-containing monooxygenase (FMO, EC 1.14.13.8). The human FMO oxygenates nucleophilic heteroatom-containing chemicals and drugs and generally converts them into harmless, polar, readily excreted metabolites. Sometimes, however, FMO bioactivates chemicals into reactive materials that can cause toxicity. Most of the interindividual differences of FMO are due to genetic variability and allelic variation, and splicing variants may contribute to interindividual and interethnic variability observed for FMO-mediated metabolism. In contrast to cytochrome P450 (CYP), FMO is not easily induced nor readily inhibited, and potential adverse drug-drug interactions are minimized for drugs prominently metabolized by FMO. These properties may provide advantages in drug design and discovery, and by incorporating FMO detoxication pathways into drug candidates, more drug-like materials may be forthcoming. Although exhaustive examples are not available, physiological factors can influence FMO function, and this may have implications for the clinical significance of FMO and a role in human disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.46.120604.141043
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  • 21
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    PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS: How Their Effects on Macrophages Can Lead to the Development of a New Drug Therapy Against Atherosclerosis (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 46 (2006), S. 1-39 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Peroxisome proliferator-activated receptors (PPARs) alpha (ʼ̛), beta/delta (?‚/??), and gamma (??) are members of the nuclear receptor superfamily, which also includes the estrogen, androgen, and glucocorticoid receptors. Recent evidence suggests that PPARs regulate genes involved in lipid metabolism, glucose homeostasis, and inflammation in various tissues; however, the mechanisms involved are not completely understood. Anti-diabetic drugs, called glitazones, can selectively activate PPAR??, and hypolipidemic drugs, called fibrates, can weakly activate PPARʼ̛. Both classes of drugs can decrease insulin resistance and dyslipidemias, which also makes them attractive for treating the metabolic syndrome. The metabolic syndrome exhibits a constellation of risk factors for atherosclerosis that include obesity, insulin resistance, dyslipidemias, and hypertension. Interestingly, all three PPARs are present in macrophages and can therefore have a profound effect on several disease processes, including atherosclerosis. Macrophages are key players in atherosclerotic lesion development. Currently, the first line of defense in reducing the risk of atherosclerosis is aimed at lowering low-density lipoproteins (LDL) and raising high-density lipoproteins (HDL), but a large percentage of patients on statins still succumb to coronary artery disease. However, with the development of drugs selectively activating PPARs, a new arsenal of drugs specifically targeting to the macrophage/foam cell may potentially have a profound impact on how we treat cardiovascular disease.
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    URL: http://dx.doi.org/10.1146/annurev.pharmtox.46.120604.141247
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    THE REGULATION AND PHARMACOLOGY OF ENDOTHELIAL NITRIC OXIDE SYNTHASE (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 46 (2006), S. 235-276 
    Details
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Nitric oxide (NO) is a small, diffusible, lipophilic free radical gas that mediates significant and diverse signaling functions in nearly every organ system in the body. The endothelial isoform of nitric oxide synthase (eNOS) is a key source of NO found in the cardiovascular system. This review summarizes the pharmacology of NO and the cellular regulation of endothelial NOS (eNOS). The molecular intricacies of the chemistry of NO and the enzymology of NOSs are discussed, followed by a review of the biological activities of NO. This information is then used to develop a more global picture of the pharmacological control of NO synthesis by NOSs in both physiologic conditions and pathophysiologic states.
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    URL: http://dx.doi.org/10.1146/annurev.pharmtox.44.101802.121844
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    CYTOCHROME P450 AND XENOBIOTIC RECEPTOR HUMANIZED MICE * (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 46 (2006), S. 41-64 
    Details
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Most xenobiotics that enter the body are subjected to metabolism that functions primarily to facilitate their elimination. Metabolism of certain xenobiotics can also result in the production of electrophilic derivatives that can cause cell toxicity and transformation. Many xenobiotics can also activate receptors that in turn induce the expression of genes encoding xenobiotic-metabolizing enzymes and xenobiotic transporters. However, there are marked species differences in the way mammals respond to xenobiotics, which are due in large part to molecular differences in receptors and xenobiotic-metabolizing enzymes. This presents a problem in extrapolating data obtained with rodent model systems to humans. There are also polymorphisms in xenobiotic-metabolizing enzymes that can impact drug therapy and cancer susceptibility. In an effort to generate more reliable in vivo systems to study and predict human response to xenobiotics, humanized mice are under development.
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    URL: http://dx.doi.org/10.1146/annurev.pharmtox.45.120403.100007
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    CHRONIC EFFECTS OF MECHANICAL FORCE ON AIRWAYS (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 563-583 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Airways are embedded in the mechanically dynamic environment of the lung. In utero, this mechanical environment is defined largely by fluid secretion into the developing airway lumen. Clinical, whole lung, and cellular studies demonstrate pivotal roles for mechanical distention in airway morphogenesis and cellular behavior during lung development. In the adult lung, the mechanical environment is defined by a dynamic balance of surface, tissue, and muscle forces. Diseases of the airways modulate both the mechanical stresses to which the airways are exposed as well as the structure and mechanical behavior of the airways. For instance, in asthma, activation of airway smooth muscle abruptly changes the airway size and stress state within the airway wall; asthma also results in profound remodeling of the airway wall. Data now demonstrate that airway epithelial cells, smooth muscle cells, and fibroblasts respond to their mechanical environment. A prominent role has been identified for the epithelium in transducing mechanical stresses, and in both the fetal and mature airways, epithelial cells interact with mesenchymal cells to coordinate remodeling of tissue architecture in response to the mechanical environment.
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    THE ASSOCIATION OF NHERF ADAPTOR PROTEINS WITH G PROTEINĐ??COUPLED RECEPTORS AND RECEPTOR TYROSINE KINASES * (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 491-505 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: The sodium-hydrogen exchanger regulatory factors (NHERF-1 and NHERF-2) are a family of adaptor proteins characterized by the presence of two tandem PDZ protein interaction domains and a C-terminal domain that binds the cytoskeleton proteins ezrin, radixin, moesin, and merlin. The NHERF proteins are highly expressed in the kidney, small intestine, and other organs, where they associate with a number of transporters and ion channels, signaling proteins, and transcription factors. Recent evidence has revealed important associations between the NHERF proteins and several G proteinĐ??coupled receptors such as the ?‚2-adrenergic receptor, the ?”-opioid receptor, and the parathyroid hormone receptor, as well as growth factor tyrosine kinase receptors such as the platelet-derived growth factor receptor and the epidermal growth factor receptor. This review summarizes the emerging data on the biochemical mechanisms, physiologic outcomes, and potential clinical implications of the assembly and disassembly of receptor/NHERF complexes.
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    URL: http://dx.doi.org/10.1146/annurev.physiol.68.040104.131050
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    CNG AND HCN CHANNELS: Two Peas, One Pod (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 375-401 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Cyclic nucleotideĐ??activated ion channels play a fundamental role in a variety of physiological processes. By opening in response to intracellular cyclic nucleotides, they translate changes in concentrations of signaling molecules to changes in membrane potential. These channels belong to two families: the cyclic nucleotideĐ??gated (CNG) channels and the hyperpolarization-activated cyclic nucleotideĐ??modulated (HCN) channels. The two families exhibit high sequence similarity and belong to the superfamily of voltage-gated potassium channels. Whereas HCN channels are activated by voltage and CNG channels are virtually voltage independent, both channels are activated by cyclic nucleotide binding. Furthermore, the channels are thought to have similar channel structures, leading to similar mechanisms of activation by cyclic nucleotides. However, although these channels are structurally and behaviorally similar, they have evolved to perform distinct physiological functions. This review describes the physiological roles and biophysical behavior of CNG and HCN channels. We focus on how similarities in structure and activation mechanisms result in common biophysical models, allowing CNG and HCN channels to be viewed as a single genre.
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    URL: http://dx.doi.org/10.1146/annurev.physiol.68.040104.134728
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    OXIDATIVE STRESS IN MARINE ENVIRONMENTS: Biochemistry and Physiological Ecology (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 253-278 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Oxidative stressĐ??the production and accumulation of reduced oxygen intermediates such as superoxide radicals, singlet oxygen, hydrogen peroxide, and hydroxyl radicalsĐ??can damage lipids, proteins, and DNA. Many disease processes of clinical interest and the aging process involve oxidative stress in their underlying etiology. The production of reactive oxygen species is also prevalent in the world's oceans, and oxidative stress is an important component of the stress response in marine organisms exposed to a variety of insults as a result of changes in environmental conditions such as thermal stress, exposure to ultraviolet radiation, or exposure to pollution. As in the clinical setting, reactive oxygen species are also important signal transduction molecules and mediators of damage in cellular processes, such as apoptosis and cell necrosis, for marine organisms. This review brings together the voluminous literature on the biochemistry and physiology of oxidative stress from the clinical and plant physiology disciplines with the fast-increasing interest in oxidative stress in marine environments.
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    THE CONTRIBUTION OF BIOPHYSICAL LUNG INJURY TO THE DEVELOPMENT OF BIOTRAUMA (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 585-618 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Patients with severe acute respiratory distress syndrome who die usually succumb to multiorgan failure as opposed to hypoxia. Despite appropriate resuscitation, some patients' symptoms persist on a downward spiral, apparently propagated by an uncontained systemic inflammatory response. This phenomenon is not well understood. However, a novel hypothesis to explain this observation proposes that it is related to the life-saving ventilatory support used to treat the respiratory failure. According to this hypothesis, mechanical ventilation per se, by alterating both the magnitude and the pattern of lung stretch, can cause changes in gene expression and/or cellular metabolism that ultimately can lead to the development of an overwhelming inflammatory responseĐ??even in the absence of overt structural damage. This mechanism of injury has been termed biotrauma. In this review we explore the biotrauma hypothesis, the causal relationship between biophysical injury and organ failure, and its implications for the future therapy and management of critically ill patients.
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    URL: http://dx.doi.org/10.1146/annurev.physiol.68.072304.113443
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    SIGNALING FOR CONTRACTION AND RELAXATION IN SMOOTH MUSCLE OF THE GUT (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 345-374 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Phosphorylation of Ser19 on the 20-kDa regulatory light chain of myosin II (MLC20) by Ca2+/calmodulin-dependent myosin light-chain kinase (MLCK) is essential for initiation of smooth muscle contraction. The initial [Ca2+]i transient is rapidly dissipated and MLCK inactivated, whereas MLC20 and muscle contraction are well maintained. Sustained contraction does not reflect Ca2+ sensitization because complete inhibition of MLC phosphatase activity in the absence of Ca2+ induces smooth muscle contraction. This contraction is suppressed by staurosporine, implying participation of a Ca2+-independent MLCK. Thus, sustained contraction, as with agonist-induced contraction at experimentally fixed Ca2+ concentrations, involves (a) G protein activation, (b) regulated inhibition of MLC phosphatase, and (c) MLC20 phosphorylation via a Ca2+-independent MLCK. The pathways that lead to inhibition of MLC phosphatase by Gq/13-coupled receptors are initiated by sequential activation of Gʼ̛q/ʼ̛13, RhoGEF, and RhoA, and involve Rho kinaseĐ??mediated phosphorylation of the regulatory subunit of MLC phosphatase (MYPT1) and/or PKC-mediated phosphorylation of CPI-17, an endogenous inhibitor of MLC phosphatase. Sustained MLC20 phosphorylation is probably induced by the Ca2+-independent MLCK, ZIP kinase. The pathways initiated by Gi-coupled receptors involve sequential activation of G?‚??i, PI 3-kinase, and the Ca2+-independent MLCK, integrin-linked kinase. The last phosphorylates MLC20 directly and inhibits MLC phosphatase by phosphorylating CPI-17. PKA and PKG, which mediate relaxation, act upstream to desensitize the receptors (VPAC2 and NPR-C), inhibit adenylyl and guanylyl cyclase activities, and stimulate cAMP-specific PDE3 and PDE4 and cGMP-specific PDE5 activities. These kinases also act downstream to inhibit (a) initial contraction by inhibiting Ca2+ mobilization and (b) sustained contraction by inhibiting RhoA and targets downstream of RhoA. This increases MLC phosphatase activity and induces MLC20 dephosphorylation and muscle relaxation.
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    TRANSCRIPTION FACTORS AND CONGENITAL HEART DEFECTS (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 97-121 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Although there have been important advances in diagnostic modalities and therapeutic strategies for congenital heart defects (CHD), these malformations still lead to significant morbidity and mortality in the human population. Over the past 10 years, characterization of the genetic causes of CHD has begun to elucidate some of the molecular causes of these defects. Linkage analysis and candidate-gene approaches have been used to identify gene mutations that are associated with both familial and sporadic cases of CHD. Complementation of the human studies with developmental studies in mouse models provides information for the roles of these genes in normal development as well as indications for disease pathogenesis. Biochemical analysis of these gene mutations has provided further insight into the molecular effects of these genetic mutations. Here we review genetic, developmental, and biochemical studies of six cardiac transcription factors that have been identified as genetic causes for CHD in humans.
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    STRESS TRANSMISSION IN THE LUNG: Pathways from Organ to Molecule (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 507-541 
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    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Gas exchange, the primary function of the lung, can come about only with the application of physical forces on the macroscale and their transmission to the scale of small airway, small blood vessel, and alveolus, where they serve to distend and stabilize structures that would otherwise collapse. The pathway for force transmission then continues down to the level of cell, nucleus, and molecule; moreover, to lesser or greater degrees most cell types that are resident in the lung have the ability to generate contractile forces. At these smallest scales, physical forces serve to distend the cytoskeleton, drive cytoskeletal remodeling, expose cryptic binding domains, and ultimately modulate reaction rates and gene expression. Importantly, evidence has now accumulated suggesting that multiscale phenomena span these scales and govern integrative lung behavior.
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    CO AS A CELLULAR SIGNALING MOLECULE (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 46 (2006), S. 411-449 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Many biological functions of heme oxygenase (HO), such as cytoprotection against oxidative stress, vasodilation, neurotransmission in the central or peripheral nervous systems, and anti-inflammatory, anti-apoptotic, or anti-proliferative potential, have been attributed to its enzymatic byproduct carbon monoxide (CO), although roles for biliverdin/bilirubin and iron have also been proposed. In addition to these well-characterized effects, recent findings reveal that HO-derived CO may act as an oxygen sensor and circadian modulator of heme biosynthesis. In lymphocytes, CO may participate in regulatory T cell function. A number of the known signaling effects of CO depend on stimulation of soluble guanylate cyclase and/or activation of mitogen-activated protein kinases (MAPK). Furthermore, modulation of caveolin-1 status may serve as an essential component of certain aspects of CO action, such as growth control. In this review, we summarize recent findings of the beneficial or detrimental effects of endogenous CO with an emphasis on the signaling pathways and downstream targets that trigger the action of this gas.
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    REGULATION OF PHOSPHOLIPASE C ISOZYMES BY RAS SUPERFAMILY GTPASES (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 46 (2006), S. 355-379 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: The physiological effects of many extracellular stimuli are mediated by receptor-promoted activation of phospholipase C (PLC) and consequential activation of inositol lipid-signaling pathways. These signaling responses include the classically described conversion of PtdIns(4,5)P2 to the Ca2+-mobilizing second messenger Ins(1,4,5)P3 and the protein kinase CĐ??activating second messenger diacylglycerol as well as alterations in membrane association or activity of many proteins that harbor phosphoinositide binding domains. Here we discuss how the family of PLCs elaborates a minimal catalytic core typified by PLC-?? to confer multiple modes of regulation on their phospholipase activities. Although PLC-dependent signaling is prominently regulated by direct interactions with heterotrimeric G proteins or tyrosine kinases, the existence of at least 13 divergent PLC isozymes promises a diverse repertoire of regulatory mechanisms for this class of important signaling proteins. We focus here on the recently realized and extensive regulation of inositol lipid signaling by Ras superfamily GTPases directly acting on PLC isozymes and conclude by considering the biological and pharmacological ramifications of this regulation.
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    REGULATION OF DRUG-METABOLIZING ENZYMES AND TRANSPORTERS IN INFLAMMATION (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 46 (2006), S. 123-149 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Inflammation and infection have long been known to downregulate the activity and expression of cytochrome P450 (CYP) enzymes involved in hepatic drug clearance. This can result in elevated plasma drug levels and increased adverse effects. Recent information on regulation of human CYP enzymes is presented, as are new developments in our understanding of the mechanisms of regulation. Experiments to study the effects of modulating CYP activities on the inflammatory response have yielded possible insights into the physiological consequences, if not the purpose, of the downregulation. Regulation of hepatic flavin monooxygenases, UDP-glucuronosyltransferases, sulfotransferases, glutathione S-transferases, as well as of hepatic transporters during the inflammatory response, exhibits similarities and differences with regulation of CYPs.
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    PHARMACOGENOMICS OF ACUTE LEUKEMIA (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 46 (2006), S. 317-353 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Over the past four decades, treatment of acute leukemia in children has made remarkable progress, from this disease being lethal to now achieving cure rates of 80% for acute lymphoblastic leukemia and 45% for acute myeloid leukemia. This progress is largely owed to the optimization of existing treatment modalities rather than the discovery of new agents. However, the annual number of patients with leukemia who experience relapse after initial therapy remains greater than that of new cases of most childhood cancers. The aim of pharmacogenetics is to develop strategies to personalize medications and tailor treatment regimens to individual patients, with the goal of enhancing efficacy and safety through better understanding of the person's genetic makeup. In this review, we summarize recent pharmacogenomic studies related to the treatment of pediatric acute leukemia. These include work using candidate-gene approaches, as well as genome-wide studies using haplotype mapping and gene expression profiling. These strategies illustrate the promise of pharmacogenomics to further advance the treatment of human cancers, with childhood leukemia serving as a paradigm.
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    THE PROTEASOME AND PROTEASOME INHIBITORS IN CANCER THERAPY (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 46 (2006), S. 189-213 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: The proteasome, a multicatalytic proteinase complex, is responsible for the majority of intracellular protein degradation. Pharmacologic inhibitors of the proteasome possess in vitro and in vivo antitumor activity, and bortezomib, the first such agent to undergo clinical testing, has significant efficacy against multiple myeloma and non-Hodgkin lymphoma (NHL). Preclinical studies demonstrate that proteasome inhibition potentiates the activity of other cancer therapeutics, in part by downregulating chemoresistance pathways. Early clinical studies of bortezomib-based combinations, showing encouraging activity, support this observation. Molecular characterization of resistance to proteasome inhibitors has revealed novel therapeutic targets for sensitizing malignancies to these agents, such as the heat shock pathway. Below, we review the pharmacologic, preclinical, and clinical data that have paved the way for the use of proteasome inhibitors for cancer therapy; outline strategies aimed at enhancing the efficacy of proteasome inhibitors; and review other potential targets in the ubiquitin proteasome pathway for the treatment of cancer.
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    MOLECULAR MECHANISM OF 7TM RECEPTOR ACTIVATIONĐ??A GLOBAL TOGGLE SWITCH MODEL (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 46 (2006), S. 481-519 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: The multitude of chemically highly different agonists for 7TM receptors apparently do not share a common binding mode or active site but nevertheless act through induction of a common molecular activation mechanism. A global toggle switch model is proposed for this activation mechanism to reconcile the accumulated biophysical data supporting an outward rigid-body movement of the intracellular segments, as well as the recent data derived from activating metal ion sites and tethered ligands, which suggests an opposite, inward movement of the extracellular segments of the transmembrane helices. According to this model, a vertical see-saw movement of TM-VIĐ??and to some degree TM-VIIĐ??around a pivot corresponding to the highly conserved prolines will occur during receptor activation, which may involve the outer segment of TM-V in an as yet unclear fashion. Small-molecule agonists can stabilize such a proposed active conformation, where the extracellular segments of TM-VI and -VII are bent inward toward TM-III, by acting as molecular glue deep in the main ligand-binding pocket between the helices, whereas larger agonists, peptides, and proteins can stabilize a similar active conformation by acting as Velcro at the extracellular ends of the helices and the connecting loops.
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    FUNCTION OF RETINOID NUCLEAR RECEPTORS: Lessons from Genetic and Pharmacological Dissections of the Retinoic Acid Signaling Pathway During Mouse Embryogenesis (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 46 (2006), S. 451-480 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Retinoic acid (RA) is involved in vertebrate morphogenesis, growth, cellular differentiation, and tissue homeostasis. The use of in vitro systems initially led to the identification of nuclear receptor RXR/RAR heterodimers as possible transducers of the RA signal. To unveil the physiological functions of RARs and RXRs, genetic and pharmacological studies have been performed in the mouse. Together, their results demonstrate that (a) RXR/RAR heterodimers in which RXR is either transcriptionally active or silent are involved in the transduction of the RA signal during prenatal development, (b) specific RXRʼ̛/RAR heterodimers are required at many distinct stages during early embryogenesis and organogenesis, (c) the physiological role of RA and its receptors cannot be extrapolated from teratogenesis studies using retinoids in excess. Additional cell typeĐ??restricted and temporally controlled somatic mutagenesis is required to determine the functions of RARs and RXRs during postnatal life.
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    CANNABINOID RECEPTORS AS THERAPEUTIC TARGETS (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 46 (2006), S. 101-122 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: CB1 and CB2 cannabinoid receptors are the primary targets of endogenous cannabinoids (endocannabinoids). These G proteinĐ??coupled receptors play an important role in many processes, including metabolic regulation, craving, pain, anxiety, bone growth, and immune function. Cannabinoid receptors can be engaged directly by agonists or antagonists, or indirectly by manipulating endocannabinoid metabolism. In the past several years, it has become apparent from preclinical studies that therapies either directly or indirectly influencing cannabinoid receptors might be clinically useful. This review considers the components of the endocannabinoid system and discusses some of the most promising endocannabinoid-based therapies.
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    REGULATION OF PLATELET FUNCTIONS BY P2 RECEPTORS (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 46 (2006), S. 277-300 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: The main role of blood platelets is to ensure primary hemostasis, which is the maintenance of vessel integrity and cessation of bleeding upon injury. While playing a major part in acute arterial thrombosis, platelets are also involved in inflammation, atherosclerosis, and angiogenesis. ADP and ATP play a crucial role in platelet activation, and their receptors are potential targets for antithrombotic drugs. The ATP-gated cation channel P2X1 and the two G proteinĐ??coupled ADP receptors, P2Y1 and P2Y12, selectively contribute to platelet aggregation and formation of a thrombus. Owing to its central role in the growth and stabilization of a thrombus, the P2Y12 receptor is an established target of antithrombotic drugs such as clopidogrel. Studies in P2Y1 and P2X1 knockout mice and selective P2Y1 and P2X1 antagonists have shown that these receptors are also attractive targets for new antithrombotic compounds. The potential role of platelet P2 receptors in the involvement of platelets in inflammatory processes is also discussed.
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    FUNCTIONAL IMAGING OF TUMOR PROTEOLYSIS (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 46 (2006), S. 301-315 
    Details
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: The roles of proteases in cancer are now known to be much broader than simply degradation of extracellular matrix during tumor invasion and metastasis. Furthermore, proteases from tumor-associated cells (e.g., fibroblasts, inflammatory cells, endothelial cells) as well as tumor cells are recognized to contribute to pathways critical to neoplastic progression. Although elevated expression (transcripts and proteins) of proteases, and in some cases protease inhibitors, has been documented in many tumors, techniques to assess functional roles for proteases require that we measure protease activity and inhibition of that activity rather than levels of proteases, activators, and inhibitors. Novel techniques for functional imaging of protease activity, both in vitro and in vivo, are being developed as are imaging probes that will allow us to determine protease activity and in some cases to discriminate among protease activities. These should be useful clinically as surrogate endpoints for therapies that alter protease activities.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.45.120403.095853
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    Electronic Resource
    ROLE OF ABCG2/BCRP IN BIOLOGY AND MEDICINE (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 46 (2006), S. 381-410 
    Details
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: The protein variously named ABCG2/BCRP/MXR/ABCP is a recently described ATP-binding cassette (ABC) transporter originally identified by its ability to confer drug resistance that is independent of Mrp1 (multidrug-resistance protein 1) and Pgp (P-glycoprotein). Unlike Mrp1 and Pgp, ABCG2 is a half-transporter that must homodimerize to acquire transport activity. ABCG2 is found in a variety of stem cells and may protect them from exogenous and endogenous toxins. ABCG2 expression is upregulated under low-oxygen conditions, consistent with its high expression in tissues exposed to low-oxygen environments. ABCG2 interacts with heme and other porphyrins and protects cells and/or tissues from protoporphyrin accumulation under hypoxic conditions. Individuals who carry ABCG2 alleles that have impaired function may be more susceptible to porphyrin-induced toxicity. Abcg2 knock-out models have allowed in vivo studies of Abcg2 function in host and cellular defense. In combination with immunohistochemical analyses, these studies have revealed how ABCG2 influences the absorption, distribution, and excretion of drugs and cytotoxins.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.46.120604.141238
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    ACCESSORY PROTEINS FOR G PROTEINS: Partners in Signaling (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 46 (2006), S. 151-187 
    Details
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Accessory proteins involved in signal processing through heterotrimeric G proteins are generally defined as proteins distinct from G proteinĐ??coupled receptor (GPCR), G protein, or classical effectors that regulate the strength/efficiency/specificity of signal transfer upon receptor activation or position these entities in the right microenvironment, contributing to the formation of a functional signal transduction complex. A flurry of recent studies have implicated an additional class of accessory proteins for this system that provide signal input to heterotrimeric G proteins in the absence of a cell surface receptor, serve as alternative binding partners for G protein subunits, provide unexpected modes of G protein regulation, and have introduced additional functional roles for G proteins. This group of accessory proteins includes the recently discovered Activators of G protein Signaling (AGS) proteins identified in a functional screen for receptor-independent activators of G protein signaling as well as several proteins identified in protein interaction screens and genetic screens in model organisms. These accessory proteins may influence GDP dissociation and nucleotide exchange at the G subunit, alter subunit interactions within heterotrimeric G independent of nucleotide exchange, or form complexes with G or G independent of the typical G heterotrimer. AGS and related accessory proteins reveal unexpected diversity in G protein subunits as signal transducers within the cell.
    Type of Medium: Electronic Resource
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    Responding to amphibian loss (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-12-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pounds, J Alan -- Carnaval, Ana Carolina -- Puschendorf, Robert -- Haddad, Celio F B -- Masters, Karen L -- New York, N.Y. -- Science. 2006 Dec 8;314(5805):1541-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17158306" target="_blank"〉PubMed〈/a〉
    Keywords: *Amphibians ; Animals ; Biodiversity ; Chytridiomycota ; Conservation of Natural Resources ; *Ecosystem ; *Environment ; Greenhouse Effect ; Mycoses/veterinary ; Population Dynamics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Plants, RNAi, and the Nobel Prize (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-11-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jorgensen, Rich -- New York, N.Y. -- Science. 2006 Nov 24;314(5803):1242-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17124307" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Nobel Prize ; Plants/*genetics ; *RNA Interference ; RNA, Double-Stranded/genetics
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    MATERIALS SCIENCE: High-Pressure Microscopy (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-05-30
    Description: When bombarded with electrons, carbon nanotubes shrink, creating high internal pressures. The effect on molecules within the tubes can be studied at atomic resolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Zhongwu -- Zhao, Yusheng -- New York, N.Y. -- Science. 2006 May 26;312(5777):1149-1150.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16731518" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Forced resonant migration of Pluto's outer satellites by Charon (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-07-11
    Description: Two small moons of Pluto have been discovered in low-eccentricity orbits exterior to Pluto's large satellite, Charon. All three satellite orbits are nearly coplanar, implying a common origin. It has been argued that Charon formed as a result of a giant impact with primordial Pluto. The orbital periods of the two new moons are nearly integer multiples of Charon's period, suggesting that they were driven outward by resonant interactions with Charon during its tidal orbital expansion. This could have been accomplished if Charon's orbit was eccentric during most of this orbital evolution, with the small moons originating as debris from the collision that produced Charon.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ward, William R -- Canup, Robin M -- New York, N.Y. -- Science. 2006 Aug 25;313(5790):1107-9. Epub 2006 Jul 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Space Studies, Southwest Research Institute, Boulder, CO 80302, USA. ward@boulder.swri.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16825533" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Sherwood Boehlert interview. Explaining science to power: make it simple, make it pay. Interview by Jeffrey Mervis (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-11-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boehlert, Sherwood -- New York, N.Y. -- Science. 2006 Nov 24;314(5803):1228-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17124296" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Atmosphere. Global change in the upper atmosphere (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-11-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lastovicka, J -- Akmaev, R A -- Beig, G -- Bremer, J -- Emmert, J T -- New York, N.Y. -- Science. 2006 Nov 24;314(5803):1253-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Atmospheric Physics, 14131 Prague, Czech Republic. jla@ufa.cas.cz〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17124313" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
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    Altruistic helping in human infants and young chimpanzees (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-03-04
    Description: Human beings routinely help others to achieve their goals, even when the helper receives no immediate benefit and the person helped is a stranger. Such altruistic behaviors (toward non-kin) are extremely rare evolutionarily, with some theorists even proposing that they are uniquely human. Here we show that human children as young as 18 months of age (prelinguistic or just-linguistic) quite readily help others to achieve their goals in a variety of different situations. This requires both an understanding of others' goals and an altruistic motivation to help. In addition, we demonstrate similar though less robust skills and motivations in three young chimpanzees.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Warneken, Felix -- Tomasello, Michael -- New York, N.Y. -- Science. 2006 Mar 3;311(5765):1301-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental and Comparative Psychology, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany. warneken@eva.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16513986" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; *Altruism ; Animals ; Behavior, Animal ; Child, Preschool ; Female ; *Helping Behavior ; Humans ; Male ; Motivation ; Pan troglodytes/*psychology
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    Applied physics. Where have all the transistors gone? (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-01-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cowburn, R P -- New York, N.Y. -- Science. 2006 Jan 13;311(5758):183-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Blackett Physics Laboratory, Imperial College London, Prince Consort Road, London SW7 2BW, UK. r.cowburn@imperial.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16410511" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Isotopic evidence for dietary variability in the early hominin Paranthropus robustus (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-11-11
    Description: Traditional methods of dietary reconstruction do not allow the investigation of dietary variability within the lifetimes of individual hominins. However, laser ablation stable isotope analysis reveals that the delta13C values of Paranthropus robustus individuals often changed seasonally and interannually. These data suggest that Paranthropus was not a dietary specialist and that by about 1.8 million years ago, savanna-based foods such as grasses or sedges or animals eating these foods made up an important but highly variable part of its diet.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sponheimer, Matt -- Passey, Benjamin H -- de Ruiter, Darryl J -- Guatelli-Steinberg, Debbie -- Cerling, Thure E -- Lee-Thorp, Julia A -- New York, N.Y. -- Science. 2006 Nov 10;314(5801):980-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anthropology, University of Colorado at Boulder, Boulder, CO 80309, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17095699" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carbon Isotopes/*analysis ; Climate ; Dental Enamel/*chemistry ; *Diet ; Ecosystem ; *Fossils ; *Hominidae ; Lasers ; *Paleodontology ; Plants ; Poaceae ; Rain ; Seasons ; South Africa
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    Coherent control of retinal isomerization in bacteriorhodopsin (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-09-02
    Description: Optical control of the primary step of photoisomerization of the retinal molecule in bacteriorhodopsin from the all-trans to the 13-cis state was demonstrated under weak field conditions (where only 1 of 300 retinal molecules absorbs a photon during the excitation cycle) that are relevant to understanding biological processes. By modulating the phases and amplitudes of the spectral components in the photoexcitation pulse, we showed that the absolute quantity of 13-cis retinal formed upon excitation can be enhanced or suppressed by +/-20% of the yield observed using a short transform-limited pulse having the same actinic energy. The shaped pulses were shown to be phase-sensitive at intensities too low to access different higher electronic states, and so these pulses apparently steer the isomerization through constructive and destructive interference effects, a mechanism supported by observed signatures of vibrational coherence. These results show that the wave properties of matter can be observed and even manipulated in a system as large and complex as a protein.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Prokhorenko, Valentyn I -- Nagy, Andrea M -- Waschuk, Stephen A -- Brown, Leonid S -- Birge, Robert R -- Miller, R J Dwayne -- R01 GM034548/GM/NIGMS NIH HHS/ -- R01 GM034548-17/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2006 Sep 1;313(5791):1257-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Optical Sciences, Departments of Chemistry and Physics, University of Toronto, 80 St. George Street, M5S3H6, Toronto, Ontario, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16946063" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Bacteriorhodopsins/*chemistry ; Halobacterium salinarum/chemistry ; Isomerism ; Kinetics ; Lasers ; *Light ; Photochemistry ; Photons ; Quantum Theory ; Retinaldehyde/*chemistry ; Thermodynamics
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    An antigen produced by splicing of noncontiguous peptides in the reverse order (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-09-09
    Description: CD8-positive T lymphocytes recognize peptides that are usually derived from the degradation of cellular proteins and are presented by class I molecules of the major histocompatibility complex. Here we describe a human minor histocompatibility antigen created by a polymorphism in the SP110 nuclear phosphoprotein gene. The antigenic peptide comprises two noncontiguous SP110 peptide segments spliced together in reverse order to that in which they occur in the predicted SP110 protein. The antigenic peptide could be produced in vitro by incubation of precursor peptides with highly purified 20S proteasomes. Cutting and splicing probably occur within the proteasome by transpeptidation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Warren, Edus H -- Vigneron, Nathalie J -- Gavin, Marc A -- Coulie, Pierre G -- Stroobant, Vincent -- Dalet, Alexandre -- Tykodi, Scott S -- Xuereb, Suzanne M -- Mito, Jeffrey K -- Riddell, Stanley R -- Van den Eynde, Benoit J -- CA106512/CA/NCI NIH HHS/ -- CA18029/CA/NCI NIH HHS/ -- P01 CA018029/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2006 Sep 8;313(5792):1444-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Immunology, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16960008" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Motifs ; Amino Acid Sequence ; Amino Acid Substitution ; *Antigen Presentation ; B-Lymphocytes/immunology ; Cell Line, Transformed ; Cytotoxicity, Immunologic ; Electroporation ; HLA-A Antigens/immunology ; Humans ; Interferon-gamma/metabolism ; Male ; Middle Aged ; Minor Histocompatibility Antigens/genetics/*immunology/*metabolism ; Molecular Sequence Data ; Nuclear Proteins/chemistry/genetics/*immunology/*metabolism ; Peptide Fragments/metabolism ; Polymorphism, Single Nucleotide ; Proteasome Endopeptidase Complex/metabolism ; *Protein Splicing ; T-Lymphocytes, Cytotoxic/*immunology
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    Scientific publishing. Hwang aftereffects reverberate at journals (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-01-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin, Jennifer -- Holden, Constance -- Chong, Sei -- New York, N.Y. -- Science. 2006 Jan 20;311(5759):321.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16424308" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cloning, Organism ; Editorial Policies ; Embryo, Mammalian/*cytology ; Humans ; *Periodicals as Topic ; *Publishing ; *Scientific Misconduct ; *Stem Cells
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    Prying open the black box (2006)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2006-10-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bloom, Floyd -- New York, N.Y. -- Science. 2006 Oct 6;314(5796):17.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17023615" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*physiology ; *Computational Biology ; Databases as Topic ; *Models, Neurological ; Neurons/*physiology ; *Neurosciences
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    Coherent electronic fringe structure in incommensurate silver-silicon quantum wells (2006)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2006-11-04
    Description: Atomically uniform silver films grown on highly doped n-type Si(111) substrates show fine-structured electronic fringes near the silicon valence band edge as observed by angle-resolved photoemission. No such fringes are observed for silver films grown on lightly doped n-type substrates or p-type substrates, although all cases exhibited the usual quantum-well states corresponding to electron confinement in the film. The fringes correspond to electronic states extending over the silver film as a quantum well and reaching into the silicon substrate as a quantum slope, with the two parts coherently coupled through an incommensurate interface structure.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Speer, N J -- Tang, S-J -- Miller, T -- Chiang, T-C -- New York, N.Y. -- Science. 2006 Nov 3;314(5800):804-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, University of Illinois at Urbana-Champaign, 1110 West Green Street, Urbana, IL 61801-3080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17082455" target="_blank"〉PubMed〈/a〉
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    A scientific supercourse (2006)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2006-04-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Laporte, Ronald E -- Omenn, Gilbert S -- Serageldin, Ismail -- Cerf, Vinton G -- Linkov, Faina -- New York, N.Y. -- Science. 2006 Apr 28;312(5773):526.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16645075" target="_blank"〉PubMed〈/a〉
    Keywords: Education, Distance ; *Global Health ; *Internet ; Public Health/*education ; Science/*education
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    Debating sexual selection and mating strategies (2006)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2006-05-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ghiselin, Michael T -- New York, N.Y. -- Science. 2006 May 5;312(5774):689-97; author reply 689-97.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16680820" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Male ; *Sexual Behavior, Animal ; *Social Behavior
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    Molecular biology. Managing associations between different chromosomes (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spilianakis, Charalampos G -- Flavell, Richard A -- New York, N.Y. -- Science. 2006 Apr 14;312(5771):207-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16614205" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Cell Nucleus/genetics/metabolism ; Chromosomes, Mammalian/*genetics/metabolism ; DNA Methylation ; DNA-Binding Proteins/*metabolism ; Fluorescent Antibody Technique ; *Gene Expression Regulation ; Genomic Imprinting ; In Situ Hybridization, Fluorescence ; Insulin-Like Growth Factor II/genetics ; Mice ; Neurofibromin 1/genetics ; RNA, Long Noncoding ; RNA, Untranslated/genetics ; Regulatory Elements, Transcriptional ; Repressor Proteins/*metabolism ; Transcription, Genetic ; Transcriptional Activation ; Ubiquitin-Protein Ligases/genetics
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Social science. Google's hidden wealth (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-11-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bohannon, John -- New York, N.Y. -- Science. 2006 Nov 10;314(5801):915.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17095670" target="_blank"〉PubMed〈/a〉
    Keywords: Ethics, Research ; Humans ; *Information Storage and Retrieval/ethics ; *Internet ; *Research ; *Social Sciences
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Characterization of the piRNA complex from rat testes (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-06-17
    Description: Small noncoding RNAs regulate processes essential for cell growth and development, including mRNA degradation, translational repression, and transcriptional gene silencing (TGS). During a search for candidate mammalian factors for TGS, we purified a complex that contains small RNAs and Riwi, the rat homolog to human Piwi. The RNAs, frequently 29 to 30 nucleotides in length, are called Piwi-interacting RNAs (piRNAs), 94% of which map to 100 defined (〈 or = 101 kb) genomic regions. Within these regions, the piRNAs generally distribute across only one genomic strand or distribute on two strands but in a divergent, nonoverlapping manner. Preparations of piRNA complex (piRC) contain rRecQ1, which is homologous to qde-3 from Neurospora, a gene implicated in silencing pathways. Piwi has been genetically linked to TGS in flies, and slicer activity cofractionates with the purified complex. These results are consistent with a gene-silencing role for piRC in mammals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lau, Nelson C -- Seto, Anita G -- Kim, Jinkuk -- Kuramochi-Miyagawa, Satomi -- Nakano, Toru -- Bartel, David P -- Kingston, Robert E -- New York, N.Y. -- Science. 2006 Jul 21;313(5785):363-7. Epub 2006 Jun 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16778019" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/isolation & purification/metabolism ; Animals ; Chromosomes, Mammalian ; Conserved Sequence ; DNA Helicases/isolation & purification/metabolism ; Gene Library ; Genome ; Male ; Mice ; Proteins/isolation & purification/*metabolism ; *RNA Interference ; RNA, Untranslated/chemistry/genetics/isolation & purification/*metabolism ; Rats ; Rats, Sprague-Dawley ; RecQ Helicases ; Ribonucleoproteins/chemistry/isolation & purification/*metabolism ; Testis/*chemistry ; Transcription, Genetic
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    Social science. Tracking people's electronic footprints (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-11-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bohannon, John -- New York, N.Y. -- Science. 2006 Nov 10;314(5801):914-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17095669" target="_blank"〉PubMed〈/a〉
    Keywords: Computer Simulation ; Group Processes ; Humans ; *Interpersonal Relations ; Mathematics ; *Social Behavior ; *Sociology ; Suicide ; Terrorism
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    Israel-Palestine science. Breaking up bomb plots--and habitats? (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-04-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bohannon, John -- New York, N.Y. -- Science. 2006 Apr 21;312(5772):354-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16627712" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biodiversity ; Conservation of Natural Resources ; *Ecosystem ; *Environment ; Israel ; Middle East ; Plants ; Politics ; *Security Measures
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Cyclopropenylidenes: from interstellar space to an isolated derivative in the laboratory (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-04-15
    Description: Like many of the molecular species that have been detected in the interstellar medium, the singlet carbene cyclopropenylidene (C3H2) has been presumed to be too unstable to isolate in the laboratory. However, by appending pi-electron-donating amino groups to the triangular skeleton, we prepared a cyclopropenylidene derivative that is stable at room temperature. In contrast to previously isolated carbenes, this compound does not require a heteroatom adjacent to the electron-deficient carbon to confer stability. Despite the presence of amino groups, the geometric parameters of the cyclic skeleton, revealed by x-ray crystallography, are only slightly perturbed relative to those of the calculated structure of unsubstituted cyclopropenylidene. Stable cyclopropenylidene derivatives might thus serve as models for a better understanding of the formation of carbon-bearing molecules in the interstellar medium.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2427275/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2427275/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lavallo, Vincent -- Canac, Yves -- Donnadieu, Bruno -- Schoeller, Wolfgang W -- Bertrand, Guy -- R01 GM 68825/GM/NIGMS NIH HHS/ -- R01 GM068825/GM/NIGMS NIH HHS/ -- R01 GM068825-01A2/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2006 May 5;312(5774):722-4. Epub 2006 Apr 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of California, Riverside-CNRS Joint Research Chemistry Laboratory (Unite Mixte Internationale 2957), Department of Chemistry, University of California, Riverside, CA 92521-0403, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16614171" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray ; Cyclopropanes/chemistry/*isolation & purification ; *Extraterrestrial Environment ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Temperature ; Thermodynamics
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    Ecology. Photosymbiosis and the evolution of modern coral reefs (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-05-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stanley, George D Jr -- New York, N.Y. -- Science. 2006 May 12;312(5775):857-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Montana Paleontology Center, Missoula, MT 59812, USA. george.stanley@umontana.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16690848" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Animals ; Anthozoa/growth & development/*physiology ; *Biological Evolution ; Calcification, Physiologic ; Calcium Carbonate/metabolism ; Carbon Dioxide/metabolism ; Climate ; *Ecosystem ; Eukaryota/growth & development/*physiology ; Fossils ; Photosynthesis ; Sunlight ; *Symbiosis
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    Paleoanthropology. Lucy's 'child' offers rare glimpse of an ancient toddler (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-09-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gibbons, Ann -- New York, N.Y. -- Science. 2006 Sep 22;313(5794):1716.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16990523" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone and Bones/anatomy & histology ; Ethiopia ; Female ; *Fossils ; *Hominidae/anatomy & histology/growth & development ; Paleodontology ; Skeleton ; Skull/anatomy & histology
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    Bioethics. Researchers attack newspaper probe of trials (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-09-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2006 Sep 22;313(5794):1714.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16990521" target="_blank"〉PubMed〈/a〉
    Keywords: Antifungal Agents/administration & dosage/therapeutic use ; Clinical Trials as Topic/*ethics ; Conflict of Interest ; Consultants ; Drug Industry ; Humans ; National Institutes of Health (U.S.) ; *Newspapers as Topic ; Research Design ; Research Personnel/*ethics ; United States
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    Women in science. MIT hiring controversy sparks faculty fracas (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-07-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lawler, Andrew -- New York, N.Y. -- Science. 2006 Jul 21;313(5785):284.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16857909" target="_blank"〉PubMed〈/a〉
    Keywords: *Faculty ; Female ; Humans ; Massachusetts ; *Neurosciences ; *Personnel Selection ; Prejudice ; Universities/*manpower ; *Women, Working
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    Molecular imaging in cancer (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-05-27
    Description: Medical imaging technologies have undergone explosive growth over the past few decades and now play a central role in clinical oncology. But the truly transformative power of imaging in the clinical management of cancer patients lies ahead. Today, imaging is at a crossroads, with molecularly targeted imaging agents expected to broadly expand the capabilities of conventional anatomical imaging methods. Molecular imaging will allow clinicians to not only see where a tumor is located in the body, but also to visualize the expression and activity of specific molecules (e.g., proteases and protein kinases) and biological processes (e.g., apoptosis, angiogenesis, and metastasis) that influence tumor behavior and/or response to therapy. This information is expected to have a major impact on cancer detection, individualized treatment, and drug development, as well as our understanding of how cancer arises.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weissleder, Ralph -- New York, N.Y. -- Science. 2006 May 26;312(5777):1168-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. weissleder@helix.mgh.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16728630" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor ; *Diagnostic Imaging ; Drug Evaluation, Preclinical ; Humans ; Indicators and Reagents ; *Molecular Diagnostic Techniques ; Neoplasms/chemistry/*diagnosis/*therapy ; Positron-Emission Tomography ; *Radiopharmaceuticals
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    Cancer. First pass at cancer genome reveals complex landscape (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-09-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2006 Sep 8;313(5792):1370.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16959977" target="_blank"〉PubMed〈/a〉
    Keywords: Breast Neoplasms/*genetics ; Colonic Neoplasms/*genetics ; Databases, Nucleic Acid ; *Genes, Neoplasm ; *Genome, Human ; Humans ; *Mutation ; Sequence Analysis, DNA
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    Cortical 5-HT2A receptor signaling modulates anxiety-like behaviors in mice (2006)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2006-07-29
    Description: Serotonin [5-hydroxytryptamine (5-HT)] neurotransmission in the central nervous system modulates depression and anxiety-related behaviors in humans and rodents, but the responsible downstream receptors remain poorly understood. We demonstrate that global disruption of 5-HT2A receptor (5HT2AR) signaling in mice reduces inhibition in conflict anxiety paradigms without affecting fear-conditioned and depression-related behaviors. Selective restoration of 5HT2AR signaling to the cortex normalized conflict anxiety behaviors. These findings indicate a specific role for cortical 5HT2AR function in the modulation of conflict anxiety, consistent with models of cortical, "top-down" influences on risk assessment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weisstaub, Noelia V -- Zhou, Mingming -- Lira, Alena -- Lambe, Evelyn -- Gonzalez-Maeso, Javier -- Hornung, Jean-Pierre -- Sibille, Etienne -- Underwood, Mark -- Itohara, Shigeyoshi -- Dauer, William T -- Ansorge, Mark S -- Morelli, Emanuela -- Mann, J John -- Toth, Miklos -- Aghajanian, George -- Sealfon, Stuart C -- Hen, Rene -- Gingrich, Jay A -- KO8 MH01711/MH/NIMH NIH HHS/ -- P01 DA12923/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 2006 Jul 28;313(5786):536-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Columbia University and the New York State Psychiatric Institute, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16873667" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anxiety/*physiopathology ; Cerebral Cortex/*metabolism ; Conditioning (Psychology) ; Conflict (Psychology) ; Depression/physiopathology ; Exploratory Behavior ; Fear ; Limbic System/metabolism ; Mice ; Mice, Knockout ; Patch-Clamp Techniques ; Periaqueductal Gray/metabolism ; Prosencephalon/metabolism ; Receptor, Serotonin, 5-HT2A/genetics/*metabolism ; Receptor, Serotonin, 5-HT2C/metabolism ; Receptors, Neurotransmitter/metabolism ; Risk-Taking ; Serotonin/physiology ; *Signal Transduction ; Synaptic Transmission
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    Running out of water--and time (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-08-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bohannon, John -- New York, N.Y. -- Science. 2006 Aug 25;313(5790):1085-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16931753" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture ; *Fresh Water ; Humans ; Middle East ; Sewage ; Water Pollutants/analysis ; *Water Purification ; *Water Supply
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    Comment on "Gene regulatory networks and the evolution of animal body plans" (2006)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2006-08-12
    Description: Davidson and Erwin (Reviews, 10 February 2006, p. 796) argued that known microevolutionary processes cannot explain the evolution of large differences in development that characterize phyla. Instead, they proposed that phyla arise from novel evolutionary processes involving large mutations acting on conserved core pathways of development. I question some of their assumptions and show that natural selection adequately explains the origin of new phyla.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coyne, Jerry A -- New York, N.Y. -- Science. 2006 Aug 11;313(5788):761; author reply 761.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolution, University of Chicago, 1101 East 57th Street, Chicago, IL 60637, USA. j-coyne@uchicago.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16902111" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; Body Patterning/*genetics ; *Gene Expression Regulation, Developmental ; *Genetic Speciation ; Morphogenesis/*genetics ; *Phylogeny ; *Selection, Genetic
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    Conductance quantization at a half-integer plateau in a symmetric GaAs quantum wire (2006)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2006-06-03
    Description: We present data from an induced gallium arsenide (GaAs) quantum wire that exhibits an additional conductance plateau at 0.5(2e2/h), where e is the charge of an electron and h is Planck's constant, in zero magnetic field. The plateau was most pronounced when the potential landscape was tuned to be symmetric by using low-temperature scanning-probe techniques. Source-drain energy spectroscopy and temperature response support the hypothesis that the origin of the plateau is the spontaneous spin-polarization of the transport electrons: a ferromagnetic phase. Such devices may have applications in the field of spintronics to either generate or detect a spin-polarized current without the complications associated with external magnetic fields or magnetic materials.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crook, R -- Prance, J -- Thomas, K J -- Chorley, S J -- Farrer, I -- Ritchie, D A -- Pepper, M -- Smith, C G -- New York, N.Y. -- Science. 2006 Jun 2;312(5778):1359-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cavendish Laboratory, 19 JJ Thomson Avenue, Cambridge CB3 0HE, UK. rc230@cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16741116" target="_blank"〉PubMed〈/a〉
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    Scientific publishing. Canadian editors fired in row with association (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-03-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Webster, Paul -- New York, N.Y. -- Science. 2006 Mar 3;311(5765):1226.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16513951" target="_blank"〉PubMed〈/a〉
    Keywords: Canada ; *Editorial Policies ; Periodicals as Topic ; *Publishing ; *Societies, Medical
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    Chemistry. Seamless proteins tie up their loose ends (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-03-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Craik, David J -- New York, N.Y. -- Science. 2006 Mar 17;311(5767):1563-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia. d.craik@imb.uq.edu.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16543448" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-HIV Agents/chemistry/pharmacology ; Anti-Infective Agents/chemistry/pharmacology ; Bacterial Proteins/biosynthesis/chemistry/pharmacology ; Codon, Terminator ; Cyclization ; Cyclotides/biosynthesis/*chemistry/pharmacology ; Defensins/biosynthesis/chemistry/genetics/pharmacology ; Drug Design ; Humans ; Peptides, Cyclic/biosynthesis/*chemistry ; Plant Proteins/biosynthesis/chemistry/pharmacology ; Protein Biosynthesis ; Protein Conformation ; Protein Denaturation ; Protein Engineering ; Protein Folding ; Protein Precursors/metabolism ; Proteins/*chemistry/metabolism/pharmacology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Chemistry. Strong-arming molecular dynamics (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-10-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rabitz, Herschel -- New York, N.Y. -- Science. 2006 Oct 13;314(5797):264-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Princeton University, Princeton, NJ 08544, USA. hrabitz@princeton.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17038613" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Israel-Palestine science. Palestinian archaeology braces for a storm (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-04-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bohannon, John -- New York, N.Y. -- Science. 2006 Apr 21;312(5772):352-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16627711" target="_blank"〉PubMed〈/a〉
    Keywords: *Archaeology ; Financial Support ; International Cooperation ; Israel ; Middle East ; Politics ; *Research ; Research Support as Topic
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  • 80
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    HIV testing and individual rights (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-10-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mills, Edward -- Rennie, Stuart -- New York, N.Y. -- Science. 2006 Oct 20;314(5798):417-9; author reply 417-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17053128" target="_blank"〉PubMed〈/a〉
    Keywords: *AIDS Serodiagnosis ; Female ; HIV Infections/*diagnosis/prevention & control ; *Human Rights ; Humans ; Male ; Mandatory Testing ; Prejudice
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 81
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    Ecology. Adding biofuels to the invasive species fire? (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-09-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Raghu, S -- Anderson, R C -- Daehler, C C -- Davis, A S -- Wiedenmann, R N -- Simberloff, D -- Mack, R N -- New York, N.Y. -- Science. 2006 Sep 22;313(5794):1742.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Illinois Natural History Survey, Champaign, IL 61820, USA. raghu@uiuc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16990536" target="_blank"〉PubMed〈/a〉
    Keywords: *Biomass ; *Conservation of Natural Resources ; *Ecosystem ; *Energy-Generating Resources ; *Environment ; Herbicides ; Pest Control, Biological ; *Poaceae/growth & development ; United States
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  • 82
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    Anthropology. Autonomous cultivation before domestication (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-06-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weiss, Ehud -- Kislev, Mordechai E -- Hartmann, Anat -- New York, N.Y. -- Science. 2006 Jun 16;312(5780):1608-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Martin (Szusz) Department of Land of Israel Studies and Archaeology and Faculty of Life Sciences, Bar-Ilan University, 52900 Ramat-Gan, Israel. eweiss@mail.biu.ac.il〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16778044" target="_blank"〉PubMed〈/a〉
    Keywords: *Anthropology ; Avena/growth & development/history ; Crops, Agricultural/growth & development/*history ; Edible Grain/growth & development/*history ; History, Ancient ; Hordeum/growth & development/history ; Lens Plant/growth & development ; Middle East ; North America ; Secale/growth & development/history
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  • 83
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    Ecology. Staying connected in a turbulent world (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-01-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Steneck, Robert S -- New York, N.Y. -- Science. 2006 Jan 27;311(5760):480-1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Marine Sciences, University of Maine, Darling Marine Center, Walpole, ME 04573, USA. steneck@maine.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16439653" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Anthozoa ; Caribbean Region ; Computer Simulation ; Conservation of Natural Resources ; *Ecosystem ; Fishes/growth & development/*physiology ; Larva/physiology ; Models, Biological ; Population Dynamics ; *Seawater ; *Swimming ; Water Movements
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    Language control in the bilingual brain (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-06-10
    Description: How does the bilingual brain distinguish and control which language is in use? Previous functional imaging experiments have not been able to answer this question because proficient bilinguals activate the same brain regions irrespective of the language being tested. Here, we reveal that neuronal responses within the left caudate are sensitive to changes in the language or the meaning of words. By demonstrating this effect in populations of German-English and Japanese-English bilinguals, we suggest that the left caudate plays a universal role in monitoring and controlling the language in use.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crinion, J -- Turner, R -- Grogan, A -- Hanakawa, T -- Noppeney, U -- Devlin, J T -- Aso, T -- Urayama, S -- Fukuyama, H -- Stockton, K -- Usui, K -- Green, D W -- Price, C J -- 051067/Wellcome Trust/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2006 Jun 9;312(5779):1537-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Department of Imaging Neuroscience, University College London, London WC1N 3BG, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16763154" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Brain Mapping ; Caudate Nucleus/*physiology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; *Multilingualism ; Neurons/physiology ; Positron-Emission Tomography ; Semantics
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    2007 U.S. budget. NASA budget soars as shuttle lands (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-07-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lawler, Andrew -- New York, N.Y. -- Science. 2006 Jul 21;313(5785):280.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16857906" target="_blank"〉PubMed〈/a〉
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    Scholarly publishing. Particle physicists want to expand open access (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-09-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2006 Sep 1;313(5791):1215.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16946040" target="_blank"〉PubMed〈/a〉
    Keywords: Fees and Charges ; *Information Dissemination ; *Periodicals as Topic/economics ; Physical Phenomena ; *Physics ; *Publishing/economics ; Societies, Scientific/economics
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    Arata Kochi profile. Fighting words from WHO's new malaria chief (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-02-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bohannon, John -- New York, N.Y. -- Science. 2006 Feb 3;311(5761):599.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16456051" target="_blank"〉PubMed〈/a〉
    Keywords: Antimalarials/pharmacology/therapeutic use ; Artemisinins/pharmacology/therapeutic use ; Developing Countries ; Drug Industry ; Drug Resistance ; Drug Therapy, Combination ; History, 20th Century ; History, 21st Century ; Humans ; Japan ; *Malaria/drug therapy/epidemiology/parasitology ; Sesquiterpenes/pharmacology/therapeutic use ; World Health Organization/*organization & administration
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    Astronomy. Testing star formation theory (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-08-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crutcher, Richard M -- New York, N.Y. -- Science. 2006 Aug 11;313(5788):771-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Astronomy, University of Illinois, 1002 W. Green Street, Urbana, IL 61801, USA. crutcher@uiuc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16902116" target="_blank"〉PubMed〈/a〉
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    Archaeology. North versus south, Mesopotamian style (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-06-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lawler, Andrew -- New York, N.Y. -- Science. 2006 Jun 9;312(5779):1458-63.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16763123" target="_blank"〉PubMed〈/a〉
    Keywords: Archaeology ; Civilization/*history ; History, Ancient ; Humans ; Syria ; Urban Population/history
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  • 90
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    Direct determination of local lattice polarity in crystals (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-06-03
    Description: With current advances in sub-angstrom resolution scanning transmission electron microscopy (STEM), it is now possible to image directly local crystal structures of materials where dramatically different atoms are separated from each other at distances about or less than 1 angstrom. We achieved direct imaging of atomic columns of nitrogen in close proximity to columns of aluminum in wurtzite aluminum nitride by using annular dark field imaging in an aberration-corrected STEM. This ability allows direct determination of the local polarity in nanoscale crystals and crystal defects.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mkhoyan, K A -- Batson, P E -- Cha, J -- Schaff, W J -- Silcox, J -- New York, N.Y. -- Science. 2006 Jun 2;312(5778):1354.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Applied and Engineering Physics, Cornell University, Ithaca, NY 14853, USA. kam55@cornell.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16741114" target="_blank"〉PubMed〈/a〉
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    Plant genotypic diversity predicts community structure and governs an ecosystem process (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-08-19
    Description: Theory predicts, and recent empirical studies have shown, that the diversity of plant species determines the diversity of associated herbivores and mediates ecosystem processes, such as aboveground net primary productivity (ANPP). However, an often-overlooked component of plant diversity, namely population genotypic diversity, may also have wide-ranging effects on community structure and ecosystem processes. We showed experimentally that increasing population genotypic diversity in a dominant old-field plant species, Solidago altissima, determined arthropod diversity and community structure and increased ANPP. The effects of genotypic diversity on arthropod diversity and ANPP were comparable to the effects of plant species diversity measured in other studies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crutsinger, Gregory M -- Collins, Michael D -- Fordyce, James A -- Gompert, Zachariah -- Nice, Chris C -- Sanders, Nathan J -- New York, N.Y. -- Science. 2006 Aug 18;313(5789):966-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, University of Tennessee, Knoxville, TN 37996, USA. gcrutsin@utk.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16917062" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Arthropods ; *Biodiversity ; *Ecosystem ; *Genetic Variation ; Genotype ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Population Density ; Solidago/*genetics/growth & development
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  • 92
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    The fluorescent toolbox for assessing protein location and function (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-04-15
    Description: Advances in molecular biology, organic chemistry, and materials science have recently created several new classes of fluorescent probes for imaging in cell biology. Here we review the characteristic benefits and limitations of fluorescent probes to study proteins. The focus is on protein detection in live versus fixed cells: determination of protein expression, localization, activity state, and the possibility for combination of fluorescent light microscopy with electron microscopy. Small organic fluorescent dyes, nanocrystals ("quantum dots"), autofluorescent proteins, small genetic encoded tags that can be complexed with fluorochromes, and combinations of these probes are highlighted.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Giepmans, Ben N G -- Adams, Stephen R -- Ellisman, Mark H -- Tsien, Roger Y -- GM 72033/GM/NIGMS NIH HHS/ -- NS27177/NS/NINDS NIH HHS/ -- RR04050/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2006 Apr 14;312(5771):217-24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Center for Microscopy and Imaging Research, Center for Research in Biological Systems, Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16614209" target="_blank"〉PubMed〈/a〉
    Keywords: Diffusion ; Enzymes/metabolism ; Fluorescence ; Fluorescence Resonance Energy Transfer ; Fluorescent Antibody Technique ; *Fluorescent Dyes/chemistry ; Genetic Techniques ; Immunohistochemistry ; *Luminescent Proteins/chemistry/genetics ; Microscopy, Electron ; *Molecular Probe Techniques ; Protein Conformation ; Protein Transport ; Proteins/*analysis/chemistry/metabolism/*physiology ; *Quantum Dots
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    2007 NASA budget. Space scientists score a modest victory in House spending bill (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-06-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lawler, Andrew -- New York, N.Y. -- Science. 2006 Jun 23;312(5781):1729.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16794048" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
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  • 94
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    Archaeology. A rising star in the trenches (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-06-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lawler, Andrew -- New York, N.Y. -- Science. 2006 Jun 9;312(5779):1462-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16763126" target="_blank"〉PubMed〈/a〉
    Keywords: Archaeology/*history ; History, 21st Century ; Syria
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  • 95
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    Sustainability. Resolving mismatches in U.S. ocean governance (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-08-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crowder, L B -- Osherenko, G -- Young, O R -- Airame, S -- Norse, E A -- Baron, N -- Day, J C -- Douvere, F -- Ehler, C N -- Halpern, B S -- Langdon, S J -- McLeod, K L -- Ogden, J C -- Peach, R E -- Rosenberg, A A -- Wilson, J A -- New York, N.Y. -- Science. 2006 Aug 4;313(5787):617-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Marine Conservation, Nicholas School of the Environment and Earth Sciences, Duke University Marine Laboratory, Beaufort, NC 28516, USA. lcrowder@duke.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16888124" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biodiversity ; *Conservation of Natural Resources ; *Ecosystem ; Environment ; Fisheries ; Fishes ; *Government Regulation ; *Marine Biology ; Oceans and Seas ; Population Dynamics ; Seawater ; United States
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    Localized temporal change of the Earth's inner core boundary (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-09-30
    Description: Compressional waves of an earthquake doublet (two events occurring in the South Sandwich Islands on 1 December 1993 and 6 September 2003), recorded at three seismic stations in Russia and Kyrgyzstan and reflected off Earth's inner core boundary, arrived at least from 39 to 70 milliseconds earlier in the 2003 event than in the 1993 event. Such changes indicate that Earth's inner core radius enlarged locally beneath middle Africa by 0.98 to 1.75 kilometers between the times of these two events. Changes of the inner core radius may be explained by either a differential motion of the inner core, assuming that irregularities are present at the inner core boundary and fixed to the inner core, or a rapid growth of the inner core by this amount.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wen, Lianxing -- New York, N.Y. -- Science. 2006 Nov 10;314(5801):967-70. Epub 2006 Sep 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Geosciences, State University of New York at Stony Brook, NY 11794, USA. Lianxing.Wen@sunysb.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17008488" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 97
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    Sara endosomes and the maintenance of Dpp signaling levels across mitosis (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-11-18
    Description: During development, cells acquire positional information by reading the concentration of morphogens. In the developing fly wing, a gradient of the transforming growth factor-beta (TGF-beta)-type morphogen decapentaplegic (Dpp) is transduced into a gradient of concentration of the phosphorylated form of the R-Smad transcription factor Mad. The endosomal protein Sara (Smad anchor for receptor activation) recruits R-Smads for phosphorylation by the type I TGF-beta receptor. We found that Sara, Dpp, and its type I receptor Thickveins were targeted to a subpopulation of apical endosomes in the developing wing epithelial cells. During mitosis, the Sara endosomes and the receptors therein associated with the spindle machinery to segregate into the two daughter cells. Daughter cells thereby inherited equal amounts of signaling molecules and thus retained the Dpp signaling levels of the mother cell.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bokel, Christian -- Schwabedissen, Anja -- Entchev, Eugeni -- Renaud, Olivier -- Gonzalez-Gaitan, Marcos -- New York, N.Y. -- Science. 2006 Nov 17;314(5802):1135-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17110576" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Division ; DNA-Binding Proteins/metabolism ; Drosophila Proteins/*metabolism ; Drosophila melanogaster/cytology/*metabolism ; Endosomes/*metabolism ; Epithelial Cells/cytology/metabolism ; *Mitosis ; Phosphorylation ; Point Mutation ; Protein-Serine-Threonine Kinases/metabolism ; Receptors, Cell Surface/metabolism ; *Signal Transduction ; Smad Proteins, Receptor-Regulated/metabolism ; Transcription Factors/metabolism ; Transforming Growth Factor beta/*metabolism ; Wings, Animal/cytology/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 98
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    The burden of brain disorders (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-04-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cruz, Marcelo -- Jenkins, Rachel -- Silberberg, Donald -- New York, N.Y. -- Science. 2006 Apr 7;312(5770):53.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16601174" target="_blank"〉PubMed〈/a〉
    Keywords: Brain Diseases/*epidemiology ; Developing Countries/*statistics & numerical data ; Health Promotion ; Humans
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 99
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    Save the lab in Montemar, Chile (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-04-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Borges, Ricardo -- Viveros, O Humberto -- Latorre, Ramon -- New York, N.Y. -- Science. 2006 Mar 31;311(5769):1866.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16574850" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biophysics/history ; Chile ; Decapodiformes ; History, 20th Century ; *Laboratories/history
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 100
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    A clamping mechanism involved in SNARE-dependent exocytosis (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-06-24
    Description: During neurotransmitter release at the synapse, influx of calcium ions stimulates the release of neurotransmitter. However, the mechanism by which synaptic vesicle fusion is coupled to calcium has been unclear, despite the identification of both the core fusion machinery [soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)] and the principal calcium sensor (synaptotagmin). Here, we describe what may represent a basic principle of the coupling mechanism: a reversible clamping protein (complexin) that can freeze the SNAREpin, an assembled fusion-competent intermediate en route to fusion. When calcium binds to the calcium sensor synaptotagmin, the clamp would then be released. SNARE proteins, and key regulators like synaptotagmin and complexin, can be ectopically expressed on the cell surface. Cells expressing such "flipped" synaptic SNAREs fuse constitutively, but when we coexpressed complexin, fusion was blocked. Adding back calcium triggered fusion from this intermediate in the presence of synaptotagmin.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Giraudo, Claudio G -- Eng, William S -- Melia, Thomas J -- Rothman, James E -- New York, N.Y. -- Science. 2006 Aug 4;313(5787):676-80. Epub 2006 Jun 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16794037" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Vesicular Transport ; Animals ; Calcium/metabolism ; Cell Membrane/metabolism ; *Exocytosis ; Glycosylphosphatidylinositols/metabolism ; HeLa Cells ; Humans ; Nerve Tissue Proteins/*metabolism ; Rats ; Recombinant Proteins/metabolism ; SNARE Proteins/*metabolism ; Synaptotagmin I/metabolism ; Synaptotagmins/metabolism ; Type C Phospholipases/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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