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  • PANGAEA  (62,799)
  • Annual Reviews
  • 2000-2004  (62,405)
  • 1990-1994  (10,191)
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  • 1
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 55 (1993), S. 209-226 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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  • 2
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 55 (1993), S. 249-265 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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  • 3
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 55 (1993), S. 289-304 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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  • 4
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 54 (1992), S. 601-618 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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  • 5
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 54 (1992), S. 799-826 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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  • 6
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 55 (1993), S. 571-573 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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  • 7
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 54 (1992), S. 885-909 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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  • 8
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 55 (1993), S. 17-54 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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  • 9
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 56 (1994), S. 237-272 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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  • 10
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 56 (1994), S. 297-319 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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  • 11
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 56 (1994), S. 349-369 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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  • 12
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 56 (1994), S. 399-417 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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  • 13
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 55 (1993), S. 661-681 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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  • 14
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 55 (1993), S. 785-817 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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  • 15
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 56 (1994), S. 649-669 
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  • 16
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 56 (1994), S. 671-689 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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  • 17
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 56 (1994), S. 711-739 
    ISSN: 0066-4278
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  • 18
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 56 (1994), S. 741-761 
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  • 19
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 56 (1994), S. 763-796 
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  • 20
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 56 (1994), S. 371-397 
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  • 21
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 56 (1994), S. 691-709 
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  • 22
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 56 (1994), S. 797-810 
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  • 23
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 56 (1994), S. 811-829 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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  • 24
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 62 (2000), S. 25-50 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract Ventricular fibrillation (VF) is the major immediate cause of sudden cardiac death. Traditionally, VF has been defined as turbulent cardiac electrical activity, which implies a large amount of irregularity in the electrical waves that underlie ventricular excitation. During VF, the heart rate is too high (〉 550 excitations/minute) to allow adequate pumping of blood. In the electrocardiogram (ECG), ventricular complexes that are ever-changing in frequency, contour, and amplitude characterize VF. This article reviews prevailing theories for the initiation and maintenance of VF, as well as its spatio-temporal organization. Particular attention is given to recent experiments and computer simulations suggesting that VF may be explained in terms of highly periodic three-dimensional rotors that activate the ventricles at exceedingly high frequency. Such rotors may show at least two different behaviors: (a) At one extreme, they may drift throughout the heart at high speeds producing beat-to-beat changes in the activation sequence. (b) At the other extreme, rotors may be relatively stationary, activating the ventricles at such high frequencies that the wave fronts emanating from them breakup at varying distances, resulting in complex spatio-temporal patterns of fibrillatory conduction. In either case, the recorded ECG patterns are indistinguishable from VF. The data discussed have paved the way for a better understanding of the mechanisms of VF in the normal, as well as the diseased, human heart. When the heart is diseased, its work is imperfectly performed: the vessels proceeding from the heart become inactive, so that you cannot feel them ... If the heart trembles, has little power and sinks, the disease is advancing and death is near. Ebers Papyrus ~3500 BC
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  • 25
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 62 (2000), S. 179-205 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract We use a comparative approach to examine some of the physiological traits that make flight possible. Comparisons of related fliers and runners suggest that fliers generally have higher aerobic metabolic capacities than runners but that the difference is highly dependent on the taxa studied. The high metabolic rates of fliers relative to runners, especially in insects, are correlated with high locomotory muscle cycle frequencies and low efficiences of conversion of metabolic power to mechanical power. We examine some factors that produce variation in flight respiration and energetics. Air temperature strongly affects the flight metabolic rate of some insects and birds. Flight speed interacts with flier mass, so that small fliers tend to exhibit a Jshaped power curve and larger fliers a U-shaped power curve. As body size increases, mass-specific aerobic flight metabolism decreases in most studies, but mass-specific power output is constant or increases, leading to an increase in efficiency with size. Intraspecific studies have revealed specific genetically based effects on flight metabolism and power output and multiple ecological correlates of flight capabilities.
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  • 26
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 62 (2000), S. 439-466 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract Thyroid hormone is essential for normal development, differentiation, and metabolic balance. Thyroid hormone action is mediated by multiple thyroid hormone receptor isoforms derived from two distinct genes. The thyroid hormone receptors belong to a nuclear receptor superfamily that also includes receptors for other small lipophilic hormones. Thyroid hormone receptors function by binding to specific thyroid hormone-responsive sequences in promoters of target genes and by regulating transcription. Thyroid hormone receptors often form heterodimers with retinoid X receptors. Heterodimerization is regulated through distinct mechanisms that together determine the specificity and flexibility of the sequence recognition. Amino-terminal regions appear to modulate thyroid hormone receptor function in an isoform-dependent manner. Unliganded thyroid hormone receptor represses transcription through recruitment of a corepressor complex, which also includes Sin3A and histone deacetylase. Ligand binding alters the conformation of the thyroid hormone receptor in such a way as to release the corepressor complex and recruit a coactivator complex that includes multiple histone acetyltransferases, including a steroid receptor family coactivator, p300/CREB-binding protein-associated factor (PCAF), and CREB binding protein (CBP). The existence of histone-modifying activities in the transcriptional regulatory complexes indicates an important role of chromatin structure. Stoichiometric, structural, and sequence-specific rules for coregulator interaction are beginning to be understood, as are aspects of the tissue specificity of hormone action. Moreover, knockout studies suggest that the products of two thyroid hormone receptor genes mediate distinct functions in vivo. The increased understanding of the structure and function of thyroid hormone receptors and their interacting proteins has markedly clarified the molecular mechanisms of thyroid hormone action.
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  • 27
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 62 (2000), S. 535-572 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract Chloride secretion is the major determinant of mucosal hydration thoughout the gastrointestinal tract, and chloride transport is also pivotal in the regulation of fluid secretion by organs that drain into the intestine. Moreover, there are pathological consequences if chloride secretion is either reduced or increased such as in cystic fibrosis and secretory diarrhea, respectively. With the molecular cloning of many of the proteins and regulatory factors that make up the chloride secretory mechanism, there have been significant advances in our understanding of this process at the cellular level. Similarly, emerging data have clarified the intercellular relationships that govern the extent of chloride secretion. The goal of our article is to review this area of investigation, with an emphasis on recent developments and their implications for the physiology and pathophysiology of chloride transport.
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  • 28
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 62 (2000), S. 595-620 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract Epithelial tissues such as kidney, lung, and breast arise through branching morphogenesis of a pre-existing epithelial structure. They share common morphological stages and a need for regulation of a similar set of developmental decisions-where to start; when, where, and in which direction to branch; and how many times to branch-decisions requiring regulation of cell proliferation, apoptosis, invasiveness, and cell motility. It is likely that similar molecular mechanisms exist for the epithelial branching program. Here we focus on the development of the collecting system of the kidney, where, from recent data using embryonic organ culture, cell culture models of branching morphogenesis, and targeted gene deletion experiments, the outlines of a working model for branching morphogenesis begin to emerge. Key branching morphogenetic molecules in this model include growth factors, transcription factors, distal effector molecules (such as extracellular matrix proteins, integrins, proteinases and their inhibitors), and genes regulating apoptosis and cell proliferation.
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  • 29
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 62 (2000), S. 723-753 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract Motor systems can adapt rapidly to changes in external conditions and to switching of internal goals. They can also adapt slowly in response to training, alterations in the mechanics of the system, and any changes in the system resulting from injury. This article reviews the mechanisms underlying short- and long-term adaptation in rhythmic motor systems. The neuronal networks underlying the generation of rhythmic motor patterns (central pattern generators; CPGs) are extremely flexible. Neuromodulators, central commands, and afferent signals all influence the pattern produced by a CPG by altering the cellular and synaptic properties of individual neurons and the coupling between different populations of neurons. This flexibility allows the generation of a variety of motor patterns appropriate for the mechanical requirements of different forms of a behavior. The matching of motor output to mechanical requirements depends on the capacity of pattern-generating networks to adapt to slow changes in body mechanics and persistent errors in performance. Afferent feedback from body and limb proprioceptors likely plays an important role in driving these long-term adaptive processes.
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  • 30
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 62 (2000), S. 755-778 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract In recent years, it has become apparent that ligand-gated ion channels (ionotropic receptors) in the neuronal plasma membrane interact via their cytoplasmic domains with a multitude of intracellular proteins. Different classes of ligand-gated channels associate with distinct sets of intracellular proteins, often through specialized scaffold proteins containing PDZ domains. These specific interactions link the receptor channel to the cortical cytoskeleton and to appropriate signal transduction pathways in the cell. Thus ionotropic receptors are components of extensive protein complexes that are likely involved in the subcellular targeting, cytoskeletal anchoring, and localized clustering of the receptors at specific sites on the neuronal surface. In addition to structural functions, receptor-associated proteins can play important roles as activity modulators or downstream effectors of ligand-gated channels.
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    Annual Review of Physiology 62 (2000), S. 825-846 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract Mortality of infants of 〈1-kg birth weight has decreased because of surfactant treatments, antenatal glucocorticoid treatments, and new ventilation strategies. However, many of these infants develop a chronic lung disease characterized by an arrest of lung development and interference with alveolarization. Antenatal glucocorticoids can induce early lung maturation clinically, but new information from transgenic and other experimental models indicates that traditional explanations for glucocorticoid effects on the developing lung are inadequate. These very preterm infants have lungs with small lung gas volumes and delicate lung tissue that are susceptible to injury with the initiation of ventilation and subsequent ventilation. Antenatal proinflammatory exposures are frequent in very preterm infants, and postnatal injury is associated with elevations of proinflammatory cytokines in the lungs. One hypothesis is that proinflammatory cytokines can promote or interfere with lung development as well as promote lung injury. Mechanisms of lung injury being characterized in the adult lung may have unique characteristics in the developing lung.
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  • 32
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 63 (2001), S. 1-14 
    ISSN: 0066-4278
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  • 33
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 63 (2001), S. 99-117 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract In order to control cell functions, hormones and neurotransmitters generate an amazing diversity of Ca2+ signals such as local and global Ca2+ elevations and also Ca2+ oscillations. In pancreatic acinar cells, cholecystokinin (CCK) stimulates secretion of digestive enzyme and promotes cell growth, whereas acetylcholine (ACh) essentially triggers enzyme secretion. Pancreatic acinar cells are a classic model for the study of CCK- and ACh-evoked specific Ca2+ signals. In addition to inositol 1,4,5 trisphosphate (IP3), recent studies have shown that cyclic ADPribose (cADPr) and nicotinic acid adenine dinucleotide phosphate (NAADP) release Ca2+ in pancreatic acinar cells. Moreover, it has also been shown that both ACh and CCK trigger Ca2+ spikes by co-activation of IP3 and ryanodine receptors but by different means. ACh uses IP3 and Ca2+, whereas CCK uses cADPr and NAADP. In addition, CCK activates phospholipase A2 and D. The concept emerging from these studies is that agonist-specific Ca2+ signals in a single target cell are generated by combination of different intracellular messengers.
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    Annual Review of Physiology 63 (2001), S. 141-164 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract The traditionally accepted theory has been that most of the biological effects of growth hormone (GH) are mediated by circulating (endocrine) insulin-like growth factor-I (IGF-I). This dogma was modified when it was discovered that most tissues express IGF-I that can act via an autocrine/paracrine fashion. In addition, both GH and IGF-I had independent effects on various target tissues. Using tissue-specific gene deletion of IGF-I in the liver, it has been shown that circulating IGF-I is predominantly liver-derived but is not essential for normal postnatal growth. Therefore, it is proposed that non-hepatic tissue-derived IGF-I may be sufficient for growth and development. Thus the original somatomedin hypothesis has undergone further modifications.
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    Annual Review of Physiology 63 (2001), S. 215-233 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract During the 1980s the purification, cloning, and expression of various forms of guanylyl cyclase (GC) revealed that they served as receptors for extracellular signals. Seven membrane forms, which presumably exist as homodimers, and four subunits of apparent heterodimers (commonly referred to as the soluble forms) are known, but in animals such as nematodes, much larger numbers of GCs are expressed. The number of transmembrane segments (none, one, or multiple) divide the GC family into three groups. Those with no or one transmembrane segment bind nitric oxide/carbon monoxide (NO/CO) or peptides. There are no known ligands for the multiple transmembrane segment class of GCs. Mutational and structural analyses support a model where catalysis requires a shared substrate binding site between the subunits, whether homomeric or heteromeric in nature. Because some cyclases or cyclase ligand genes lack specific GC inhibitors, disruption of either has been used to define the functions of individual cyclases, as well as to define human genetic disease counterparts.
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    Annual Review of Physiology 63 (2001), S. 235-257 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract Ionic currents activated by hyperpolarization and regulated by cyclic nucleotides were first discovered more than 20 years ago. Recently the molecular identity of the underlying channels has been unveiled. The structural features of the protein sequences are discussed and related to the mechanisms of activation, selectivity for cyclic nucleotides, and ion permeation. Coverage includes a comparison of the biophysical properties of recombinant and native channels and their significance for the physiological functions of these channels.
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    Annual Review of Physiology 63 (2001), S. 119-139 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Gastric epithelial organization and function are controlled and maintained by a variety of endocrine and paracrine mediators. Peptides encoded by the gastrin gene are an important part of this system because targeted deletion of the gene, or of the gastrin-CCKB receptor gene, leads to decreased numbers of parietal cells and decreased gastric acid secretion. Recent studies indicate that the gastrin precursor, preprogastrin, gives rise to a variety of products, each with a distinctive spectrum of biological activity. The conversion of progastrin to smaller peptides is regulated by multiple mechanisms including prohormone phosphorylation and secretory vesicle pH. Progastrin itself stimulates colonic epithelial proliferation; biosynthetic intermediates (Gly-gastrins) stimulate colonic epithelial proliferation and gastric epithelial differentiation; and C-terminally amidated gastrins stimulate colonic proliferation, gastric epithelial proliferation and differentiation, and acid secretion. The effects of progastrin-derived peptides on gastric epithelial function are mediated in part by release of paracrine factors that include histamine, epidermal growth factor (EGF)-receptor ligands, and Reg. The importance of the appropriate regulation of this system is shown by the observation that prolonged moderate hypergastrinemia in transgenic mice leads to remodelling of the gastric epithelium, and in the presence of Helicobacter, to gastric cancer.
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    Annual Review of Physiology 63 (2001), S. 165-192 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract There was a time when the classification of sex hormones was simple. Androgens were male and estrogens female. What remains true today is that in young adults androgen levels are higher in males and estrogen levels higher in females. More recently we have learned that estrogens are necessary in males for regulation of male sexual behavior, maintenance of the skeleton and the cardiovascular system, and for normal function of the testis and prostate. The importance of androgen in females was never in doubt, it is after all the precursor of estrogen as the substrate for aromatase, the enzyme that produces estrogen. In addition, the tissue distribution of androgen receptors suggests that androgens themselves are important in the ovary, uterus, breast, and brain. New information promises to clarify some of the complex issues of the physiological roles of estrogen and the contribution of estrogen to the development of neoplastic diseases in humans. The discovery of the second estrogen receptor, the creation of mutant mice defective in both estrogen receptors and in the aromatase gene, the solution of the structures of the ligand-binding domains of estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta), the finding of novel routes through which estrogen receptors can modulate transcription, and the identification of a man with a bi-allelic disruptive mutation of the ERalpha gene are but some of the milestones. This review focuses on the mechanistic aspects of signal transduction mediated by ERs and on the physiological consequences of deficiency of estrogen or estrogen receptor in the available mouse models.
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    Annual Review of Physiology 63 (2001), S. 359-390 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract Marine teleosts at high latitudes can encounter ice-laden seawater that is approximately 1oC colder than the colligative freezing point of their body fluids. They avoid freezing by producing small antifreeze proteins (AFPs) that adsorb to ice and halt its growth, thereby producing an additional non-colligative lowering of the freezing point. AFPs are typically secreted by the liver into the blood. Recently, however, it has become clear that AFP isoforms are produced in the epidermis (skin, scales, fin, and gills) and may serve as a first line of defense against ice propagation into the fish. The basis for the adsorption of AFPs to ice is something of a mystery and is complicated by the extreme structural diversity of the five antifreeze types. Despite the recent acquisition of several AFP three-dimensional structures and the definition of their ice-binding sites by mutagenesis, no common ice-binding motif or even theme is apparent except that surface-surface complementarity is important for binding. The remarkable diversity of antifreeze types and their seemingly haphazard phylogenetic distribution suggest that these proteins might have evolved recently in response to sea level glaciation occurring just 1-2 million years ago in the northern hemisphere and 10-30 million years ago around Antarctica. Not surprisingly, the expression of AFP genes from different origins can also be quite dissimilar. The most intensively studied system is that of the winter flounder, which has a built-in annual cycle of antifreeze expression controlled by growth hormone (GH) release from the pituitary in tune with seasonal cues. The signal transduction pathway, transcription factors, and promoter elements involved in this process are just beginning to be characterized.
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    Annual Review of Physiology 63 (2001), S. 471-494 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract There is increasing evidence suggesting that formation of the tracheobronchial tree and alveoli results from heterogeneity of the epithelial-mesenchymal interactions along the developing respiratory tract. Recent genetic data support this idea and show that this heterogeneity is likely the result of activation of distinct networks of signaling molecules along the proximal-distal axis. Among these signals, fibroblast growth factors, retinoids, Sonic hedgehog, and transforming growth factors appear to play prominent roles. We discuss how these and other pattern regulators may be involved in initiation, branching, and differentiation of the respiratory system.
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    Annual Review of Physiology 64 (2002), S. 407-429 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract Recent discoveries have revolutionized our conceptions of enzyme-substrate specificity in signal transduction pathways. Protein kinases A and C are localized to discreet subcellular regions, and this localization changes in an isozyme-specific manner upon activation, a process referred to as translocation. The mechanisms for translocation involve interactions of soluble kinases with membrane-bound anchor proteins that recognize individual kinase isoenzymes and their state of activation. Recently, modulation of kinase-anchor protein interactions has been used to specifically regulate, positively or negatively, the activity of C kinase isozymes. Also described in this review is a role for the Rab family of small G proteins in regulating subcellular protein trafficking. The pathophysiological significance of disrupted subcellular protein transport in cell signaling and the potential therapeutic utility of targeted regulation of these events are in the process of being characterized.
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    Annual Review of Physiology 64 (2002), S. 1-18 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: This article gives a history of the evidence (a) that animal cell membranes contain pumps that expel sodium ions in exchange for potassium ions; (b) that the pump derives energy from the hydrolysis of ATP; (c) that it is thermodynamically reversible-artificially steep transmembrane ion gradients make it run backward synthesizing ATP from ADP and orthophosphate; (d) that its mechanism is a ping-pong one, in which phosphorylation of the pump by ATP is associated with an efflux of three sodium ions, and hydrolysis of the phosphoenzyme is associated with an influx of two potassium ions; (e) that each half of the working cycle involves both the transfer of a phosphate group and a conformational change-the phosphate transfer being associated with the occlusion of ions bound at one surface and the conformational change releasing the occluded ions at the opposite surface.
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    Annual Review of Physiology 63 (2001), S. 871-894 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract A variety of isoforms of mammalian voltage-gated sodium channels have been described. Ten genes encoding sodium channel alpha subunits have been identified, and nine of those isoforms have been functionally expressed in exogenous systems. The alpha subunit is associated with accessory beta subunits in some tissues, and three genes encoding different beta subunits have been identified. The alpha subunit isoforms have distinct patterns of development and localization in the nervous system, skeletal and cardiac muscle. In addition, many of the isoforms demonstrate subtle differences in their functional properties. However, there are no clear subfamilies of the channels, unlike the situation with potassium and calcium channels. The subtle differences in the functional properties of the sodium channel isoforms result in unique conductances in specific cell types, which have important physiological effects for the organism. Small alterations in the electrophysiological properties of the channel resulting from mutations in specific isoforms cause human diseases such as periodic paralysis, long QT syndrome, and epilepsy.
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    Annual Review of Physiology 64 (2002), S. 635-661 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract Bile salts are the major organic solutes in bile and undergo extensive enterohepatic circulation. Hepatocellular bile salt uptake is mediated predominantly by the Na+-taurocholate cotransport proteins Ntcp (rodents) and NTCP (humans) and by the Na+-independent organic anion-transporting polypeptides Oatp1, Oatp2, and Oatp4 (rodents) and OATP-C (humans). After diffusion (bound by intracellular bile salt-binding proteins) to the canalicular membrane, monoanionic bile salts are secreted into bile canaliculi by the bile salt export pump Bsep (rodents) or BSEP (humans). Both belong to the ATP-binding cassette (ABC) transporter superfamily. Dianionic conjugated bile salts are secreted into bile by the multidrug-resistance-associated proteins Mrp2/MRP2. In bile ductules, a minor portion of protonated bile acids and monomeric bile salts are reabsorbed by non-ionic diffusion and the apical sodium-dependent bile salt transporter Asbt/ASBT, transported back into the periductular capillary plexus by Mrp3/MRP3 [and/or a truncated form of Asbt (tAsbt)], and subjected to cholehepatic shunting. The major portion of biliary bile salts is aggregated into mixed micelles and transported into the intestine, where they are reabsorbed by apical Oatp3, the apical sodium-dependent bile salt transporter (ASBT), cytosolic intestinal bile acid-binding protein (IBABP), and basolateral Mrp3/MRP3 and tAsbt. Transcriptional and posttranscriptional regulation of these enterohepatic bile salt transporters is closely related to the regulation of lipid and cholesterol homeostasis. Furthermore, defective expression and function of bile salt transporters have been recognized as important causes for various cholestatic liver diseases.
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 62 (2000), S. 947-950 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Annual Review of Physiology 62 (2000), S. 961-963 
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    Annual Review of Physiology 65 (2003), S. 735-759 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract In Drosophila photoreceptors, the light-sensitive current is mediated downstream of phospholipase C by TRP (transient receptor potential) channels. Recent evidence suggests that Drosophila TRP channels are activated by diacylglycerol (DAG) or its metabolites (polyunsaturated fatty acids), possibly in combination with the reduction in phosphatidyl inositol 4,5 bisphosphate (PIP2). Consistent with this view, diacylglycerol kinase is identified as a key enzyme required for response termination. Signaling is critically dependent upon efficient PIP2 synthesis; mutants of this pathway in combination with genetically targeted PIP2 reporters provide unique insights into the kinetics and regulation of PIP2 turnover. Recent evidence indicates that a growing number of mammalian TRP homologues are also regulated by lipid messengers, including DAG, arachidonic acid, and PIP2.
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    Annual Review of Physiology 65 (2003), S. 701-734 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Maintenance of membrane lipid asymmetry is a dynamic process that influences many events over the lifespan of the cell. With few exceptions, most cells restrict the bulk of the aminophospholipids to the inner membrane leaflet by means of specific transporters. Working in concert with each other, these proteins correct for sporadic incursions of the aminophospholipids to the outer membrane leaflet as a result of bilayer imbalances created by various cellular events. A shift in the relative contribution in each of these activities can result in sustained exposure of the aminophospholipids at the cell surface, which allows capture of the cells by phagocytes before the integrity of the plasma membrane is compromised. The absence of an efficient recognition and elimination mechanism can result in uncontrolled and persistent presentation of self-antigens to the immune system, with development of autoimmune syndromes. To prevent this, phagocytes have developed a diverse array of distinct and redundant receptor systems that drive the postphagocytic events along pathways that facilitate cross-talk between the homeostatic and the immune systems. In this work, we review the basis for the proposed mechanism(s) by which apoptotic ligands appear on the target cell surface and the phagocyte receptors that recognize these moieties.
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    Annual Review of Physiology 65 (2003), S. 761-789 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Phosphoinositides [PPIs, which collectively refer to phosphorylated derivatives of phosphatidylinositol (PI)] have a pivotal role as precursors to important second messengers and as bona fide signaling and scaffold targeting molecules. This review focuses on recent advances that elucidate how PPIs, particularly PI(4,5)P2 (PIP2), directly regulate the actin cytoskeleton in vivo by modulating the activity and targeting of actin regulatory proteins. The role of PIP2 in stimulating actin polymerization and in establishing cytoskeleton-plasma membrane linkages is emphasized. In addition, the review presents tantalizing evidence that suggests how binding of selected cytoskeletal proteins to membrane PPIs may promote PPI clustering into raft lipid microdomains, alter their accessibility to other proteins, and even distort the bilayer conformation. These actions have profound implications for many other PPI-regulated membrane functions that are beginning to be uncovered, and they suggest how PPIs can mediate crosstalk between the actin cytoskeleton and an expanding spectrum of essential cellular functions.
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    Annual Review of Physiology 65 (2003), S. 851-879 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Rhodopsin is a retinal photoreceptor protein of bipartite structure consisting of the transmembrane protein opsin and a light-sensitive chromophore 11-cis-retinal, linked to opsin via a protonated Schiff base. Studies on rhodopsin have unveiled many structural and functional features that are common to a large and pharmacologically important group of proteins from the G protein-coupled receptor (GPCR) superfamily, of which rhodopsin is the best-studied member. In this work, we focus on structural features of rhodopsin as revealed by many biochemical and structural investigations. In particular, the high-resolution structure of bovine rhodopsin provides a template for understanding how GPCRs work. We describe the sensitivity and complexity of rhodopsin that lead to its important role in vision.
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    Annual Review of Physiology 66 (2004), S. 239-274 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Although it is well established that during periods of torpor heterothermic mammals and birds can reduce metabolic rates (MR) substantially, the mechanisms causing the reduction of MR remain a controversial subject. The comparative analysis provided here suggests that MR reduction depends on patterns of torpor used, the state of torpor, and body mass. Daily heterotherms, which are species that enter daily torpor exclusively, appear to rely mostly on the fall of body temperature (Tb) for MR reduction, perhaps with the exception of very small species and at high torpor Tb, where some metabolic inhibition may be used. In contrast, hibernators (species capable of prolonged torpor bouts) rely extensively on metabolic inhibition, in addition to Tb effects, to reduce MR to a fraction of that observed in daily heterotherms. In small hibernators, metabolic inhibition and the large fall of Tb are employed to maximize energy conservation, whereas in large hibernators, metabolic inhibition appears to be employed to facilitate MR and Tb reduction at torpor onset. Over the ambient temperature (Ta) range where torpid heterotherms are thermo-conforming, the Tb-Ta differential is more or less constant despite a decline of MR with Ta; however, in thermo-regulating torpid individuals, the Tb-Ta differential is maintained by a proportional increase of MR as during normothermia, albeit at a lower Tb. Thermal conductance in most torpid thermo-regulating individuals is similar to that in normothermic individuals despite the substantially lower MR in the former. However, conductance is low when deeply torpid animals are thermo-conforming probably because of peripheral vasoconstriction.
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    Annual Review of Physiology 66 (2004), S. 447-475 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: One of the central questions in neurobiology is how experience modifies neural function, and how changes in the nervous system permit an animal to adapt its behavior to a changing environment. Learning and adaptation to a host of different environmental stimuli exemplify processes we know must alter the nervous system because the behavioral output changes after experience. Alterations in behavior after exposure to addictive drugs are a striking example of chemical alterations of nervous system function producing long-lasting changes in behavior. The alterations produced in the central nervous system (CNS) by addictive drugs are of interest because of their relationship to human substance abuse but also because these CNS alterations produce dramatic, easily observed alterations in behavior in response to discrete stimuli. Considerable study has been given to behavioral and biochemical correlates of addiction over the past 50 or more years; however, our understanding of the cellular physiological responses of affected CNS neurons is in its infancy. This review focuses on alterations in cellular and synaptic physiology in the ventral tegmental area (VTA) in response to addictive drugs.
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    Annual Review of Physiology 66 (2004), S. 477-519 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: The intrinsic electrical properties of neurons are shaped in large part by the action of voltage-gated ion channels. Molecular cloning studies have revealed a large family of ion channel genes, many of which are expressed in mammalian brain. Much recent effort has focused on determining the contribution of the protein products of these genes to neuronal function. This requires knowledge of the abundance and distribution of the constituent subunits of the channels in specific mammalian central neurons. Here we review progress made in recent studies aimed at localizing specific ion channel subunits using in situ hybridization and immunohistochemistry. We then discuss the implications of these results in terms of neuronal physiology and neuronal mechanisms underlying the observed patterns of expression.
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    Annual Review of Physiology 66 (2004), S. 521-545 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Given their prominent actin-rich subcellular specializations, it is no surprise that mechanosensitive hair cells of the inner ear exploit myosin molecules-the only known actin-dependent molecular motors-to carry out exotic but essential tasks. Recent experiments have confirmed that an unconventional myosin isozyme, myosin-1c, is a component of the hair cell's adaptation-motor complex. This complex carries out slow adaptation, provides tension to sensitize transduction channels, and may participate in assembly of the transduction apparatus. This review focuses on the detailed operation of the adaptation motor and the functional consequences of the incorporation of this specific myosin isozyme into the motor complex.
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    Annual Review of Physiology 66 (2004), S. 625-645 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Classical experiments in embryology have shown that normal growth, morphogenetic patterning, and cellular differentiation in the developing lung depend on interactive signaling between the endodermal epithelium and mesenchyme derived from splanchnic mesoderm. These interactions are mediated by a myriad of diffusible factors that are precisely regulated in their temporal and spatial expression. In this review we first describe factors regulating formation of the embryonic foregut. We then discuss the experiments demonstrating the importance of tissue interactions in lung patterning and differentiation. Finally, we detail the roles that a few key signaling systems-fibroblast growth factors and their receptors, sonic hedgehog and Gli genes, Wnt genes and beta-catenin, and BMP4-play as mediators of epithelial-mesenchymal interactions in the developing lung.
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    Annual Review of Physiology 66 (2004), S. 799-828 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: This review is divided into two parts, the first dealing with the cell and molecular biology of muscle in terms of growth and wasting and the second being an account of current knowledge of physiological mechanisms involved in the alteration of size of the human muscle mass. Wherever possible, attempts have been made to interrelate the information in each part and to provide the most likely explanation for phenomena that are currently only partially understood. The review should be of interest to cell and molecular biologists who know little of human muscle physiology and to physicians, physiotherapists, and kinesiologists who may be familiar with the gross behavior of human muscle but wish to understand more about the underlying mechanisms of change.
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    Annual Review of Physiology 64 (2002), S. 129-152 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract All cells have the capacity to respond to chemical and sensory stimuli. Central to many such signaling pathways is the heterotrimeric G protein, which transmits a signal from cell surface receptors to intracellular effectors. Recent studies using the yeast Saccharomyces cerevisiae have produced important advances in our understanding of G protein activation and inactivation. This review focuses on the mechanisms by which G proteins transmit a signal from peptide pheromone receptors to the mating response in yeast and how mechanisms elucidated in yeast can provide insights to signaling events in more complex organisms.
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    Annual Review of Physiology 64 (2002), S. 189-222 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract The olfactory system sits at the interface of the environment and the nervous system and is responsible for correctly coding sensory information from thousands of odorous stimuli. Many theories existed regarding the signal transduction mechanism that mediates this difficult task. The discovery that odorant transduction utilizes a unique variation (a novel family of G protein-coupled receptors) based upon a very common theme (the G protein-coupled adenylyl cyclase cascade) to accomplish its vital task emphasized the power and versatility of this motif. We now must understand the downstream consequences of this cascade that regulates multiple second messengers and perhaps even gene transcription in response to the initial interaction of ligand with G protein-coupled receptor.
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    Annual Review of Physiology 64 (2002), S. 153-187 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Phototransduction is the process by which a photon of light captured by a molecule of visual pigment generates an electrical response in a photoreceptor cell. Vertebrate rod phototransduction is one of the best-studied G protein signaling pathways. In this pathway the photoreceptor-specific G protein, transducin, mediates between the visual pigment, rhodopsin, and the effector enzyme, cGMP phosphodiesterase. This review focuses on two quantitative features of G protein signaling in phototransduction: signal amplification and response timing. We examine how the interplay between the mechanisms that contribute to amplification and those that govern termination of G protein activity determine the speed and the sensitivity of the cellular response to light.
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    Annual Review of Physiology 64 (2002), S. 313-353 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Spines are neuronal protrusions, each of which receives input typically from one excitatory synapse. They contain neurotransmitter receptors, organelles, and signaling systems essential for synaptic function and plasticity. Numerous brain disorders are associated with abnormal dendritic spines. Spine formation, plasticity, and maintenance depend on synaptic activity and can be modulated by sensory experience. Studies of compartmentalization have shown that spines serve primarily as biochemical, rather than electrical, compartments. In particular, recent work has highlighted that spines are highly specialized compartments for rapid large-amplitude Ca2+ signals underlying the induction of synaptic plasticity.
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    Annual Review of Physiology 64 (2002), S. 563-594 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Multiple organic anion transporters in the proximal tubule of the kidney are involved in the secretion of drugs, toxic compounds, and their metabolites. Many of these compounds are potentially hazardous on accumulation, and it is therefore not surprising that the proximal tubule is also an important target for toxicity. In the past few years, considerable progress has been made in the cloning of these transporters and their functional characterization following heterologous expression. Members of the organic anion transporter (OAT), organic anion transporting polypeptide (OATP), multidrug resistance protein (MRP), sodium-phosphate transporter (NPT), and peptide transporter (PEPT) families have been identified in the kidney. In this review, we summarize our current knowledge on their localization, molecular and functional characteristics, and substrate and inhibitor specificity. A major challenge for the future will be to understand how these transporters work in concert to accomplish the renal secretion of specific anionic substrates.
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    Annual Review of Physiology 64 (2002), S. 663-680 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Hereditary hemochromatosis (HH) is a common inborn error of iron metabolism characterized by excess dietary iron absorption and iron deposition in several tissues. Clinical consequences include hepatic failure, hepatocellular carcinoma, diabetes, cardiac failure, impotence, and arthritis. Despite the discovery of the mutation underlying most cases of HH, considerable uncertainty exists in the mechanism by which the normal gene product, HFE, regulates iron homeostasis. Knockout of the HFE gene clearly confers the HH phenotype on mice. However, studies on HFE expressed in cultured cells have not yet clarified the mechanism by which HFE mutations lead to increased dietary iron absorption. Recent discoveries suggest other genes, including a second transferrin receptor and the circulating peptide hepcidin, participate in a shared pathway with HFE in regulation of iron absorption. This review summarizes our current understanding of the relationship between iron stores and absorption and presents models to explain the dysregulated iron homeostasis in HH.
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    Annual Review of Physiology 64 (2002), S. 749-774 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Endothelial nitric oxide synthase (eNOS) is expressed in vascular endothelium, airway epithelium, and certain other cell types where it generates the key signaling molecule nitric oxide (NO). Diminished NO availability contributes to systemic and pulmonary hypertension, atherosclerosis, and airway dysfunction. Complex mechanisms underly the cell specificity of eNOS expression, and co- and post-translational processing leads to trafficking of the enzyme to plasma membrane caveolae. Within caveolae, eNOS is the downstream target member of a signaling complex in which it is functionally linked to both typical G protein-coupled receptors and less typical receptors such as estrogen receptor (ER) alpha and the high-density lipoprotein receptor SR-BI displaying novel actions. This compartmentalization facilitates dynamic protein-protein interactions and calcium- and phosphorylation-dependent signal transduction events that modify eNOS activity. Further understanding of these mechanisms will enable us to take preventive and therapeutic advantage of the powerful actions of NO in multiple cell types.
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    Annual Review of Physiology 64 (2002), S. 877-897 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract The epithelial sodium channel (ENaC) expressed in aldosterone-responsive epithelial cells of the kidney and colon plays a critical role in the control of sodium balance, blood volume, and blood pressure. In lung, ENaC has a distinct role in controlling the ionic composition of the air-liquid interface and thus the rate of mucociliary transport. Loss-of-function mutations in ENaC cause a severe salt-wasting syndrome in human pseudohypoaldosteronism type 1 (PHA-1). Gain-of-function mutations in ENaC beta and gamma subunits cause pseudoaldosteronism (Liddle's syndrome), a severe form of salt-sensitive hypertension. This review discusses genetically defined forms of a salt sensitivity and salt resistance in human monogenic diseases and in animal models mimicking PHA-1 or Liddle's syndrome. The complex interaction between genetic factors (ENaC mutations) and the risk factor (salt intake) can now be studied experimentally. The role of single-nucleotide polymorphisms (SNPs) in determining salt sensitivity or salt resistance in general populations is one of the main challenges of the post-genomic era.
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    Annual Review of Physiology 65 (2003), S. 45-79 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Cardiac hypertrophy is the heart's response to a variety of extrinsic and intrinsic stimuli that impose increased biomechanical stress. While hypertrophy can eventually normalize wall tension, it is associated with an unfavorable outcome and threatens affected patients with sudden death or progression to overt heart failure. Accumulating evidence from studies in human patients and animal models suggests that in most instances hypertrophy is not a compensatory response to the change in mechanical load, but rather is a maladaptive process. Accordingly, modulation of myocardial growth without adversely affecting contractile function is increasingly recognized as a potentially auspicious approach in the prevention and treatment of heart failure. In this review, we summarize recent insights into hypertrophic signaling and consider several novel antihypertrophic strategies. The same thing that makes you live can kill you in the end. -Neil Young
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    Annual Review of Physiology 65 (2003), S. 161-175 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Conventional kinesin is the prototypic member of a family of diverse proteins that use the chemical energy of ATP hydrolysis to generate force and move along microtubules. These proteins, which are involved in a wide range of cellular functions, have been identified in protozoa, fungi, plants, and animals and possess a high degree of sequence conservation among species in their motor domains. The biochemical properties of kinesin and its homologues, in conjunction with the recently solved three-dimensional structures of several kinesin motors, have contributed to our understanding of the mechanism of kinesin movement along microtubules. We discuss several models for movement, including the hand-over-hand, inchworm, and biased diffusion models of processive movement, as well as models of nonprocessive movement.
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    Annual Review of Physiology 65 (2003), S. 177-201 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract This review addresses the mechanisms by which mitochondrial structure and function are regulated, with a focus on vertebrate muscle. We consider the adaptive remodeling that arises during physiological transitions such as differentiation, development, and contractile activity. Parallels are drawn between such phenotypic changes and the pattern of change arising over evolutionary time, as suggested by interspecies comparisons. We address the physiological and evolutionary relationships between ATP production, thermogenesis, and superoxide generation in the context of mitochondrial function. Our discussion of mitochondrial structure focuses on the regulation of membrane composition and maintenance of the three-dimensional reticulum. Current studies of mitochondrial biogenesis strive to integrate muscle functional parameters with signal transduction and molecular genetics, providing insight into the origins of variation arising between physiological states, fiber types, and species.
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    Annual Review of Physiology 65 (2003), S. 203-230 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Comparative physiology has proven a powerful approach to our understanding of how animals function under hypoxic conditions and to identifying potential adaptations to environmental oxygen levels. This review considers the potential for using a similar comparative approach with functional genomics to understand the genetic basis of such physiological processes and evolutionary adaptations. Comparative functional genomics is currently limited by genome data, which are available for only a few model organisms. However, comparative studies between model organisms of the same species having slightly different genomes (e.g., in-bred strains of laboratory rodents, transgenic mice, and consomic rats) demonstrate the types of results, as well as the analytical challenges, that are possible if comparative functional genomics is applied to more species. Results from wild and domestic animal studies suggest new models to investigate physiological and evolutionary responses to oxygen levels with functional genomics.
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    Annual Review of Physiology 65 (2003), S. 231-259 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract DNA microarray technology is revolutionizing many aspects of biological research, allowing the expression of many thousands of gene transcripts to be monitored simultaneously. This provides powerful tools for the genome-wide correlation of gene transcript levels with physiological responses and alterations in physiological states. To date, microarray analyses have been applied almost exclusively to a few model species for which the abundant gene sequence data permit the fabrication of whole-genome microarrays. However, many interesting physiological traits and responses are poorly expressed or absent in model species and may be better illustrated in nonmodel organisms. Comparative approaches to understanding function traditionally focus on species that by virtue of their unusual adaptations, lifestyles, and phylogeny are particularly suited to address a specific biological process or problem. In this review, we show that microarray technology can be successfully applied to these nonmodel species and used to generate new insights of comparative and evolutionary significance into animal function.
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 543-566 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract Urea plays a key role in the urine-concentrating mechanism. Physiologic and molecular data demonstrate that urea transport in kidney and red blood cells occurs by specific urea transporter proteins. Two gene families for facilitated urea transporters, UT-A and UT-B, and several urea transporter cDNA isoforms have been cloned from human, rat, mouse, and several non-mammalian species. Polyclonal antibodies have been generated to many of the urea transporter proteins, and several novel findings have resulted from their use in integrative animal studies. For example, (a) vasopressin increases the phosphorylation of UT-A1 in rat inner medullary collecting duct; (b) UT-A1 protein abundance is increased in the rat inner medulla during conditions in which urine-concentrating ability is reduced; and (c) urea transporters are expressed in non-renal tissues, and UT-A protein abundance is up-regulated in uremia in both liver and heart. In addition to the facilitated urea transporters, functional evidence exists for active urea transport in the kidney collecting duct. This review summarizes the physiologic evidence for the existence of facilitated and active urea transporters, the molecular biology of the facilitated urea transporter gene families and cDNAs, and integrative studies into urea transporter protein regulation, both in the kidney and in other organs.
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    Annual Review of Physiology 66 (2004), S. 1-27 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: This article is mostly about the beginnings of the molecular biology of membranes, covering the decade 1964-1974. It is difficult to read (or write) this article because of a sense of deja vu. Most of the material in it is considered commonplace today, having been established experimentally since then. But at the time this work was begun, practically nothing was known about the molecular structure and the mechanisms of the functions of membranes. This situation existed because no membrane proteins of the kind I called integral had as yet been isolated in a pure state, and therefore none had had their amino acid sequence determined. The first integral membrane protein to be so characterized was human erythrocyte glycophorin, in 1978. It was the use of the thermodynamic reasoning that had been developed for the study of water-soluble proteins, together with the information from several key experiments carried out in a number of laboratories during the early decade, that led us to the fluid mosaic model of membrane structure in 1972. Without direct evidence to confirm the model in 1971-1972, my colleagues and I nevertheless had the confidence in it to pursue some of the consequences of the model for a new understanding of many membrane functions, which I present here in some detail. Finally, I discuss two recent high-resolution X-ray crystallographic studies of integral proteins to ask how well the structural and functional proposals that we derived from the fluid mosaic model fit these remarkably detailed X-ray results.
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    Annual Review of Physiology 66 (2004), S. 29-48 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Heart failure remains a leading cause of hospital admissions and mortality in the elderly, and current interventional approaches often fail to treat the underlying cause of pathogenesis. Preservation of structure and function in the aging myocardium is most likely to be successful via ongoing cellular repair and replacement, as well as survival of existing cardiomyocytes that generate contractile force. Research has led to a paradigm shift driven by application of stem cells to generate cardiovascular cell lineages. Early controversial findings of pluripotent precursors adopting cardiac phenotypes are now widely accepted, and current debate centers upon the efficiency of progenitor cell incorporation into the myocardium. Much work remains to be done in determining the relevant progenitor cell population and optimizing conditions for efficient differentiation and integration. Significant implications exist for treatment of pathologically damaged or aging myocardium since future interventional approaches will capitalize upon the use of cardiac stem cells as therapeutic reagents.
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    Annual Review of Physiology 66 (2004), S. 131-159 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Potassium (K+) channels exist in all three domains of organisms: eubacteria, archaebacteria, and eukaryotes. In higher animals, these membrane proteins participate in a multitude of critical physiological processes, including food and fluid intake, locomotion, stress response, and cognitive functions. Metabolic regulatory factors such as O2, CO2/pH, redox equivalents, glucose/ATP/ADP, hormones, eicosanoids, cell volume, and electrolytes regulate a diverse group of K+ channels to maintain homeostasis.
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    Annual Review of Physiology 66 (2004), S. 183-207 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Studies investigating the effects of temperature, food availability, or other physical factors on the physiology of marine animals have led to the development of biochemical indicators of growth rate, metabolic condition, and physiological stress. Measurements of metabolic enzyme activity and RNA/DNA have been especially valuable as indicators of condition in studies of marine invertebrates and fishes, groups for which accurate determination of field metabolic rates is difficult. Properly calibrated and applied, biochemical indicators have been successfully used in studies of rocky intertidal ecology, where two decades of experimentation have generated rigorous, testable models for determining the relative influences of biotic and abiotic factors on species distribution, abundance, and interaction. Biochemical indicators of condition and metabolic activity (metabolic enzymes, RNA/DNA) have been used to test nutrient-productivity models by demonstrating tight linkages between nearshore oceanographic processes (such as upwelling) and benthic rocky intertidal ecosystems. Indices of condition and heat stress (heat shock proteins, or Hsps) have begun to be used to test environmental stress models by comparing condition, activity, and Hsp expression of key rocky intertidal predator and prey species. Using biochemical indicators of condition and stress in natural systems holds great promise for understanding mechanisms by which organisms respond to rapid environmental change.
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    Annual Review of Physiology 66 (2004), S. 291-313 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: The past decade has witnessed a growing interest in estrogens and their activity in the central nervous system, which was originally believed to be restricted to the control of reproduction. It is now well accepted that estrogens modulate the activity of all types of neural cells through a multiplicity of mechanisms. Estrogens, by binding to two cognate receptors ERalpha and ERbeta, may interact with selected promoters to initiate the synthesis of target proteins. Alternatively, the hormone receptor complex may interfere with intracellular signaling at both cytoplasmic and nuclear levels. The generation of cellular and animal models, combined with clinical and epidemiological studies, has allowed us to appreciate the neurotrophic and neuroprotective effects of estrogens. These findings are of major interest because estradiol might become an important therapeutic agent to maintain neural functions during aging and in selected neural diseases.
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    Annual Review of Anthropology 22 (1993), S. 395-423 
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    Annual Review of Anthropology 23 (1994), S. 1-24 
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    Annual Review of Anthropology 23 (1994), S. 55-82 
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    Annual Review of Anthropology 23 (1994), S. 137-158 
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    Annual Review of Anthropology 23 (1994), S. 457-480 
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    Annual Review of Anthropology 23 (1994), S. 483-506 
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    Annual Review of Anthropology 23 (1994), S. 325-345 
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    Annual Review of Anthropology 19 (1990), S. 1-15 
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    Annual Review of Anthropology 29 (2000), S. 329-355 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Ethnic Sciences , Biology
    Notes: Abstract This review inverts the idiom "family values" to show the value of the family. It grounds this value in family economic activity but advocates an interactive approach in which cultural commitments to the family influence economic and political outcomes. Historical and ethnographic research on the family is mustered to illustrate the interaction and then combined with theories of capitalism and nationalism to account for the resonance of the family values discourse. A final section reviews the potential dangers of family-focused research. That tradesman who does not delight in his family will never long delight in his business. D. Defoe
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    Annual Review of Anthropology 19 (1990), S. 89-117 
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    Annual Review of Anthropology 19 (1990), S. 39-58 
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    Annual Review of Anthropology 19 (1990), S. 119-150 
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    Annual Review of Anthropology 19 (1990), S. 187-210 
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    Annual Review of Anthropology 19 (1990), S. 151-186 
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    Annual Review of Anthropology 19 (1990), S. 211-242 
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    Annual Review of Anthropology 19 (1990), S. 283-307 
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    Annual Review of Anthropology 19 (1990), S. 261-282 
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    Annual Review of Anthropology 19 (1990), S. 309-330 
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    Annual Review of Anthropology 19 (1990), S. 353-394 
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    Annual Review of Anthropology 19 (1990), S. 331-351 
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    Annual Review of Anthropology 19 (1990), S. 419-451 
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    Annual Review of Anthropology 19 (1990), S. 395-417 
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    Annual Review of Anthropology 31 (2002), S. 69-97 
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    Topics: Ethnic Sciences , Biology
    Notes: Abstract Because of their deafness, deaf people have been marked as different and treated problematically by their hearing societies. Until 25 years ago, academic literature addressing deafness typically described deafness as pathology, focusing on cures or mitigation of the perceived handicap. In ethnographic accounts, interactions involving deaf people are sometimes presented as examples of how communities treat atypical members. Recently, studies of deafness have adopted more complex sociocultural perspectives, raising issues of community identity, formation and maintenance, and language ideology. Anthropological researchers have approached the study of d/Deaf communities from at least three useful angles. The first, focusing on the history of these communities, demonstrates that the current issues have roots in the past, including the central role of education in the creation and maintenance of communities. A second approach centers on emic perspectives, drawing on the voices of community members themselves and accounts of ethnographers. A third perspective studies linguistic issues and how particular linguistic issues involving deaf people articulate with those of their hearing societies. To use a cultural definition is not only to assert a new frame of reference, but to consciously reject an older one.... But the cultural definition continues to perplex many. If Deaf people are indeed a cultural group, why then don't they seem more like the Pennan of the island of Borneo, or the Huichol of Mexico? Carol Padden (1996a)
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    Annual Review of Anthropology 20 (1991), S. 167-186 
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    Annual Review of Anthropology 20 (1991), S. 187-209 
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