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  • Annual Reviews
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  • 101
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 62 (2000), S. 825-846 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 102
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 63 (2001), S. 1-14 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 103
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 63 (2001), S. 99-117 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 104
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 63 (2001), S. 141-164 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 105
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 63 (2001), S. 215-233 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 106
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 63 (2001), S. 235-257 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 107
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 63 (2001), S. 119-139 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 108
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 63 (2001), S. 165-192 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 109
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 59 (1997), S. 573-574 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 110
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 59 (1997), S. 575-599 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract Physical forces of gravity, hemodynamic stresses, and movement play a critical role in tissue development. Yet, little is known about how cells convert these mechanical signals into a chemical response. This review attempts to place the potential molecular mediators of mechanotransduction (e.g. stretch-sensitive ion channels, signaling mollecules, cytoskeleton, integrins) within the context of the structural complexity of living cells. The model presented relies on recent experimental findings, which suggests that cells use tensegrity architecture for their organization. Tensegrity predicts that cells are hard-wired to respond immediately to mechanical stresses transmitted over cell surface receptors that physically couple the cytoskeleton to extracellular matrix (e.g. integrins) or to other cells (cadherins, selectins, CAMs). Many signal transducing molecules that are activated by cell binding to growth factors and extracellular matrix associate with cytoskeletal scaffolds within focal adhesion complexes. Mechanical signals, therefore, may be integrated with other environmental signals and transduced into a biochemical response through force-dependent changes in scaffold geometry or molecular mechanics. Tensegrity also provides a mechanism to focus mechanical energy on molecular transducers and to orchestrate and tune the cellular response.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 111
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 63 (2001), S. 359-390 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 112
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 63 (2001), S. 471-494 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 113
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 5 (1943), S. 207-228 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 114
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 5 (1943), S. 229-252 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 115
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 5 (1943), S. 321-344 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 116
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 5 (1943), S. 1-16 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 117
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 59 (1997), S. 633-657 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract Although mechanosensory responses are ubiquitous and diverse, the molecular bases of mechanosensation in most cases remain mysterious.MscL, a mechano-sensitive channel of large conductance of Escherichia coli and its bacterial homologues are the first and currently only channel molecules shown to directly sense mechanical stretch of the membrane. In response to the tension conveyed via the lipid bilayer, MscL increases its open probability by several orders of magnitude. In the present review we describe the identification, cloning, and first sets of biophysical and structural data on this simplest mechanosensory molecule. We discovered a 2.5-ns mechanosensitive conductance in giant E. coli spheroplasts. Using chromatographies to enrich the target and patch clamp to assay the channel activity in liposome-reconstituted fractions, we identified the MscL protein and cloned the mscL gene. MscL comprises 136 amino acid residues (15 kDa), with two highly hydrophobic regions, and resides in the inner membrane of the bacterium. PhoA-fusion experiments indicate that the protein spans the membrane twice with both termini in the cytoplasm. Spectroscopic techniques show that it is highly helical. Expression of MscL tandems and covalent cross-linking suggest that the active channel complex is a homo-hexamer. We have identified several residues, which when deleted or substituted, affect channel kinetics or mechanosensitivity. Although unique when discovered, highly conserved MscL homologues in both gram-negative and gram-positive bacteria have been found, suggesting their ubiquitous importance among bacteria.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 118
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 5 (1943), S. 63-78 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 119
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 5 (1943), S. 105-122 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 120
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 5 (1943), S. 133-156 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 121
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 5 (1943), S. 253-274 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 122
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 5 (1943), S. 181-206 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 123
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 5 (1943), S. 275-294 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 124
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 64 (2002), S. 407-429 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 125
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 64 (2002), S. 1-18 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 126
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 63 (2001), S. 871-894 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 127
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 64 (2002), S. 635-661 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 128
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 60 (1998), S. 143-159 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract The intercellular tight junction is the rate-limiting barrier in the paracellular pathway for permeation by ions and larger solutes. A variety of widely used electrical and flux approaches are used in the analyses of solute permeation through this pathway; however, each has limitations in practice. It is now clear that solute permeation across tight junctions is dynamically regulated by intracellular events with a common effector mechanism apparently tied to the cytoskeleton. These pathways, which regulate tight junction solute permeability, are targets that produce epithelial barrier dysfunction in a variety of disease states. However, regulation of solute permeation across the junctional barrier may also represent a potential means to improve bioavailability of orally administered bioactive solutes.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 129
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 60 (1998), S. 161-177 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract The tight junction (TJ) is not randomly located on the cell membrane, but occupies a precise position at the outermost edge of the intercellular space and, therefore, is itself considered a polarized structure. This article reviews the most common experimental approaches for studying this relationship. We then discuss three main topics. (a) The mechanisms of polarization that operate regardless of the presence of TJs: We explore a variety of polarization mechanisms that operate at stages of the cell cycle in which TJs may be already established. (b) TJs and polarity as partners in highly dynamic processes: Polarity and TJs are steady state situations that may be drastically changed by a variety of signaling events. (c) Polarized distribution of membrane molecules that depend on TJs: This refers to molecules (mainly lipids) whose polarized distribution, although not the direct result of TJs, depends on these structures to maintain such distribution.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 130
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 60 (1998), S. 243-266 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract This review focuses on sodium-independent transport systems for organic cations in small intestine, liver, kidney, and brain. The roles of P-glycoproteins (MDR) and anion transporters (OATP) in organic cation transport are reported, and two members of the new transporter family OCT are described. The OCT transporters belong to a superfamily that includes multidrug-resistance proteins, facilitative diffusion systems, and proton antiporters. They mediate electrogenic transport of small organic cations with different molecular structures, independently of sodium and proton gradients. The current knowledge of the distribution and functional properties of cloned cation transport systems and of cation transport measured in intact plasma membranes is used to postulate identical or homologous transporters in intestine, liver, kidney, and brain.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 131
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 60 (1998), S. 179-197 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract Calcium and sodium absorption by the kidney normally proceed in parallel. However, a number of physiological, pharmacological, pathological, and genetic conditions dissociate this relation. In each instance, the dissociation can be traced to the distal convoluted tubule, where calcium and sodium transport are inversely related. Based on the identification of the relevant sodium transporters in these cells and on analysis of the mechanism of calcium transport, an explanation for this inverse relation can be developed. Apical membrane calcium entry is mediated by voltage-sensitive calcium channels that are activated upon membrane hyperpolarization. Basolateral calcium efflux is effected primarily by Na+/Ca2+ exchange. According to the model, inhibition of sodium entry through either the Na-Cl cotransporter or the Na+ channel hyperpolarizes the cell, as does parathyroid hormone, thereby activating the calcium entry channel and increasing the driving force for diffusional entry. Membrane hyperpolarization also increases the driving force of calcium efflux through the Na+/Ca2+ exchanger. Thus sodium-dependent changes of calcium transport are indirect and occur secondarily through effects on membrane voltage.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 132
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 60 (1998), S. 199-220 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract Since the molecular identification of the first aquaporin in 1992, the number of proteins known to belong to this family has been rapidly increasing. These members may be separated into two subgroups based on gene structure, sequence homology, and function. Regulation of the water permeability of the collecting ducts of the kidney is essential for urinary concentration. Aquaporin-2 and -3, which are representative of these subgroups, are colocalized in the collecting ducts. Understanding these subgroups will elucidate the differences between aquaporin-2 and -3. Aquaporin-2 is a vasopressin-regulated water channel located in the apical membrane, and aquaporin-3 is a constitutive water channel located in the basolateral membrane. In contrast to aquaporin-3, which appears to be less well regulated, many studies have now identified multiple regulational mechanisms at the gene, protein, and cell levels for aquaporin-2, thus reflecting its physiological importance. Evidence of the participation of aquaporin-2 in the pathophysiology of water-balance disorders is accumulating.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 133
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 60 (1998), S. 221-242 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract Despite the fact that prostaglandins (PGs) have low intrinsic permeabilities across the plasma membrane, they must cross it twice: first upon release from the cytosol into the blood, and again upon cellular uptake prior to oxidation. Until recently, there were no cloned carriers that transported PGs. PGT is a broadly-expressed, 12-membrane-spanning domain integral membrane protein. When heterologously expressed in HeLa cells or Xenopus oocytes, it catalyzes the rapid, specific, and high-affinity uptake of PGE2, PGF2alpha, PGD2, 8-iso-PGF2alpha, and thromboxane B2. Functional studies indicate that PGT transports its substrate as the charged anion. The PGT substrate specificity and inhibitor profile match remarkably well with earlier in situ studies on the metabolic clearance of PGs by rat lung. Because PGT expression is especially high in this tissue, it is likely that PGT mediates the membrane step in PG clearance by the pulmonary circulation. Evidence is presented that PGT may play additional roles in other tissues and that there may be additional PG transporters yet to be identified molecularly.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 134
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 60 (1998), S. 267-286 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract The discovery in the chick embryo that a specific region of the neural crest, termed the cardiac neural crest, is essential for septation of the cardiac outflow tract and for aortic arch artery development has led to the classification of a whole series of human cardiac defects as neural crest-associated. Recently, several mouse genetic models have been effectively employed to yield new insights into the relationship between cardiac neural crest and structural heart development. In all the animal models of neural crest-related heart defects, prenatal mortality is too high to be attributed to structural defects of the heart alone, and there are obvious signs of severe cardiac dysfunction. The evidence indicates that poor viability is from impaired cardiac excitation-contraction coupling and contractile function at the myocyte level. The continued study of experimental and genetically defined models with neural crest-associated heart defects will prove useful in identifying the common pathways by which the neural crest contributes to normal heart development.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 135
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 60 (1998), S. 287-308 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract Recent discoveries have led to a greater appreciation of the diverse mechanisms that underlie cardiac morphogenesis. Genetic strategies (primarily gene targeting approaches in mice) have significantly broadened research in cardiovascular developmental biology by illuminating new pathways involved in heart development and by allowing the genetic evaluation of pathways that have previously been implicated in these events. Advances have also been made using biochemical and cell- and tissue-based approaches. This review summarizes the author's interpretation of current trends in the effort to understand the molecular basis of cardiac development, with an emphasis on insights obtained from genetic models.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 136
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 62 (2000), S. 947-950 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 137
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 62 (2000), S. 961-963 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 138
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 735-759 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 139
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 701-734 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 140
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 761-789 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 141
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 851-879 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 142
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 66 (2004), S. 239-274 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 143
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 60 (1998), S. 407-429 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract Gonadal hormones are known to act during development to establish permanent sex differences in the anatomy and function of the vertebrate brain. They also act on the adult brain to activate reproductive behaviors. However, there are wide gaps in our understanding of how sexually dimorphic neural circuits translate into sex differences in behavior and other CNS functions. Moreover, not all sexually dimorphic properties of the adult brain can be attributed to known effects of gonadal hormones during development or adulthood, and factors other than gonadal steroids may contribute to these sex differences. This paper reviews sexual differentiation and the role of gonadal steroids and non-gonadal factors on sexually dimorphic development of the avian brain.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 144
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 60 (1998), S. 497-523 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract In mammals the male sex determination switch is controlled by a single gene on the Y chromosome, SRY. SRY encodes a protein with an HMG-like DNA-binding domain, which probably acts as a local organizer of chromatin structure. It is believed to regulate downstream genes in the sex determination cascade, although no direct targets of SRY are clearly known. More genes in the pathway have been isolated through mutation approaches in mouse and human. At least three genes, SRY itself, SOX9, and DAX1, are dosage sensitive, providing molecular evidence that the sex determination step operates at a critical threshold. SRY initiates development of a testis from the bipotential cells of the early gonad. The dimorphic male and female pathways present a rare opportunity to link a pivotal gene in development with morphogenetic mechanisms that operate to pattern an organ and the differentiation of its cells. Mechanisms of testis organogenesis triggered downstream of SRY include pathways of cell signaling controlling cell reorganization, cell proliferation, cell migration, and vascularization.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 145
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 60 (1998), S. 525-532 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 146
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 60 (1998), S. 461-496 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract The luteinizing hormone receptor (LHR) is a member of the subfamily of glycoprotein hormone receptors within the superfamily of G protein-coupled receptor (GPCR)/seven-transmembrane domain receptors. Over the past eight years, major advances have been made in determining the structure and function of the LHR and its gene. The hormone-binding domain has been localized to exons 1-7 in the extracellular (EC) domain/region of the receptor, which contains several leucine-rich repeats. High-affinity binding of LH and human chorionic gonadotropin (hCG) causes secondary hormone or receptor contacts to be established with regions of the EC loop/transmembrane module that initiate signal transduction. Models of hormone-receptor interaction have been derived from the crystal structures of hCG and of the ribonuclease inhibitor, which also contains leucine-rich repeats. Such models provide a framework for the interpretation of mutational studies and for further experiments. The extracellular domain of the receptor has been overexpressed in vitro, which will facilitate crystallographic resolution of the structure of the receptor-binding site. The transmembrane domain/loop/cytoplasmic module transduces the signal for couplingto G proteins. Several constitutive, activating mutations that cause human disease have been found in helix VI and adjacent structures. These mutations have provided valuable information about mechanisms of signal transfer and G protein coupling. The structure of the LHR gene has been elucidated, and the regulation of its transcription is beginning to be understood. Valuable insights into receptor evolution have been derived from analysis of sequence homologies, the gene structure of glycoprotein hormone receptors and other members of the GPCR family, and the glycoprotein hormone receptor-like precursors identified in several invertebrate species.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 147
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 60 (1998), S. 533-573 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract Since the discovery that cells can activate their own suicide program, investigators have attempted to determine whether the events that are associated with this form of cell death are genetically determined. The discovery that the ced-3 gene of Caenorhabditis elegans encodes a cysteine protease essential for developmentally regulated apoptosis ignited interest in this area of research. As a result, we now know that cell death is specified by a number of genes and that this biologic process contributes significantly to development, tumorigenesis, and autoimmune disease. In this review I summarize what is currently known about signaling pathways involved in apoptosis, with particular emphasis on the function of the cysteine proteases known as caspases. However, there is also evidence that protease-independent cell death pathways exist. Is there a relationship between these two distinct mechanisms? If so, how do they communicate? Finally, even though the involvement of tumor necrosis factor/nerve growth factor family of receptors and cysteine proteases has been elegantly established as a component of many apoptotic signaling pathways, what happens downstream of these initial events? Why are only a selected group of cellular proteins-many nuclear-the targets of these proteases? Are nuclear events essential for apoptosis in vivo? Are the cellular genes that encode products involved in apoptotic signaling frequent targets of mutation/alteration during tumorigenesis? These are only a few questions that may be answered in the next ten years.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 148
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 60 (1998), S. 575-600 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract The proto-oncogene c-myc encodes a transcription factor c-Myc, which is of great importance in controlling cell growth and vitality. The quantity of c-Myc is carefully controlled by many mechanisms, and its actions to induce and repress genes are modulated by interactions with other regulatory proteins. Understanding the kinetic and quantitative relationships that determine how and what genes c-Myc regulates is essential to understanding how Myc is involved in apoptosis. Reduction of c-myc expression and its inappropriate expression can be associated with cellular apoptosis. This review outlines the nature and regulation of the c-myc gene and of c-Myc and presents the systems and conditions in which Myc-related apoptotic events occur. Hypotheses of the mechanisms by which expression and repression of c-myc lead to apoptosis are discussed.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 149
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 60 (1998), S. 601-617 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Abstract Tissue homeostasis requires a balance between cell proliferation and death. Apoptosis and proliferation are linked by cell cycle regulators, and apoptotic stimuli affect both cell proliferation and death. Glucocorticoids induce G1 arrest and apoptosis in transformed lymphoid cells. Decreased expression of the cell cycle components c-myc and cyclin D3 is essential for glucocorticoid-induced growth arrest and death in dividing cells. Other G1 regulators, such as p53, pRb, and E2F, have also been implicated in apoptosis. Mice lacking either p53 or E2F display aberrant cell proliferation and tumor formation, suggesting that these proteins are involved in the elimination of abnormal cells through apoptosis. In contrast, pRb induces G1 arrest and suppresses apoptosis in cultured cells. Mice that lack pRb are nonviable and show ectopic mitosis and massive cell death, suggesting that pRb is an apoptotic suppressor. Further analysis of common components of apoptotic and cell cycle machinery may provide insight into the coordinated regulation of these antagonistic processes.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 150
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 67 (2005), S. 491-514 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: Vision at absolute threshold is based on signals produced in a tiny fraction of the rod photoreceptors. This requires that the rods signal the absorption of single photons, and that the resulting signals are transmitted across the retina and encoded in the activity sent from the retina to the brain. Behavioral and ganglion cell sensitivity has often been interpreted to indicate that these biophysical events occur noiselessly, i.e., that vision reaches limits to sensitivity imposed by the division of light into discrete photons and occasional photon-like noise events generated in the rod photoreceptors. We argue that this interpretation is not unique and provide a more conservative view of the constraints behavior and ganglion cell experiments impose on phototransduction and retinal processing. We summarize what is known about how these constraints are met and identify some of the outstanding open issues.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 151
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 68 (2006), S. 159-191 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 152
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 66 (2004), S. 447-475 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 153
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 66 (2004), S. 477-519 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 154
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 66 (2004), S. 521-545 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 155
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 66 (2004), S. 625-645 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 156
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 7 (1945), S. 163-180 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 157
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 7 (1945), S. 231-274 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 158
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 7 (1945), S. 275-304 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 159
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 7 (1945), S. 305-330 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 160
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    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 7 (1945), S. 389-404 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 161
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    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 7 (1945), S. 365-388 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 162
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 7 (1945), S. 455-470 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 163
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 7 (1945), S. 471-508 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 164
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    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 7 (1945), S. 509-526 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 165
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    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 7 (1945), S. 599-622 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 166
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    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 7 (1945), S. 623-652 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 167
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    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 7 (1945), S. 567-598 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 168
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    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 7 (1945), S. 677-706 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 169
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    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 8 (1946), S. 17-42 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 170
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    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 8 (1946), S. 89-98 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 171
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    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 8 (1946), S. 65-88 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 172
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    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 8 (1946), S. 145-168 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 173
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    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 8 (1946), S. 263-296 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 174
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    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 8 (1946), S. 355-374 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 175
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 8 (1946), S. 451-466 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 176
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 8 (1946), S. 535-558 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 177
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    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 66 (2004), S. 799-828 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 178
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    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 9 (1947), S. 149-162 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 179
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    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 9 (1947), S. 119-148 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 180
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    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 9 (1947), S. 255-300 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 181
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    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 9 (1947), S. 409-428 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 182
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 9 (1947), S. 457-476 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 183
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 9 (1947), S. 553-569 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 184
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 64 (2002), S. 129-152 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 185
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    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 64 (2002), S. 189-222 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 186
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 64 (2002), S. 153-187 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 187
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 64 (2002), S. 313-353 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 188
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    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 64 (2002), S. 563-594 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 189
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    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 64 (2002), S. 663-680 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 190
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    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 64 (2002), S. 749-774 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 191
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    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 64 (2002), S. 877-897 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 192
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    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 45-79 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 193
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    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 161-175 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 194
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 177-201 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 195
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 203-230 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 196
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 231-259 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 197
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 65 (2003), S. 543-566 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 198
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 66 (2004), S. 1-27 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 199
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 66 (2004), S. 29-48 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 66 (2004), S. 131-159 
    ISSN: 0066-4278
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Biologie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
    BibTip Andere fanden auch interessant ...
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