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  • Articles  (61,558)
  • American Association for the Advancement of Science  (58,802)
  • Annual Reviews  (1,877)
  • Blackwell Publishing Ltd  (879)
  • 2005-2009  (25,644)
  • 1980-1984  (16,511)
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  • Medicine  (61,558)
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  • Articles  (61,558)
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  • 1
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 21 (2005), S. 457-483 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The field of lymphatic research has been recently invigorated by the identification of genes and mechanisms that control various aspects of lymphatic development. We are beginning to understand how, starting from a subgroup of embryonic venous endothelial cells, the whole lymphatic system forms in a stepwise manner. The generation of genetically engineered mice with defects in different steps of the lymphangiogenic program has provided models that are increasing our understanding of the lymphatic system in health and disease. This knowledge, in turn, should lead to the development of better diagnostic methods and treatments of lymphatic disorders and tumor metastasis.
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  • 2
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 21 (2005), S. 1-33 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: In this review I describe the several stages of my research career, all of which were driven by a desire to understand the basic mechanisms responsible for the complex and beautiful organization of the eukaryotic cell. I was originally trained as an electron microscopist in Argentina, and my first major contribution was the introduction of glutaraldehyde as a fixative that preserved the fine structure of cells, which opened the way for cytochemical studies at the EM level. My subsequent work on membrane-bound ribosomes illuminated the process of cotranslational translocation of polypeptides across the ER membrane and led to the formulation, with Gunter Blobel, of the signal hypothesis. My later studies with many talented colleagues contributed to an understanding of ER structure and function and aspects of the mechanisms that generate and maintain the polarity of epithelial cells. For this work my laboratory introduced the now widely adopted Madin-Darby canine kidney (MDCK) cell line, and demonstrated the polarized budding of envelope viruses from those cells, providing a powerful new system that further advanced the field of protein traffic.
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  • 3
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 21 (2005), S. 133-153 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Chromatin can be differentiated by the deposition of variant histones at centromeres, active genes, and silent loci. Variant histones are assembled into nucleosomes in a replication-independent manner, in contrast to assembly of bulk chromatin that is coupled to replication. Recent in vitro studies have provided the first glimpses of protein machines dedicated to building and replacing alternative nucleosomes. They deposit variant H2A and H3 histones and are targeted to particular functional sites in the genome. Differences between variant and canonical histones can have profound consequences, either for delivery of the histones to sites of assembly or for their function after incorporation into chromatin. Recent studies have also revealed connections between assembly of variant nucleosomes, chromatin remodeling, and histone post-translational modification. Taken together, these findings indicate that chromosome architecture can be highly dynamic at the most fundamental level, with epigenetic consequences.
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  • 4
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 21 (2005), S. 203-222 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Plants shape their organs with a precision demanded by optimal function; organ shaping requires control over cell wall expansion anisotropy. Focusing on multicellular organs, I survey the occurrence of expansion anisotropy and discuss its causes and proposed controls. Expansion anisotropy of a unit area of cell wall is characterized by the direction and degree of anisotropy. The direction of maximal expansion rate is usually regulated by the direction of net alignment among cellulose microfibrils, which overcomes the prevailing stress anisotropy. In some stems, the directionality of expansion of epidermal cells is controlled by that of the inner tissue. The degree of anisotropy can vary widely as a function of position and of treatment. The degree of anisotropy is probably controlled by factors in addition to the direction of microfibril alignment. I hypothesize that rates of expansion in maximal and minimal directions are regulated by distinct molecular mechanisms that regulate interactions between matrix and microfibrils.
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  • 5
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 21 (2005), S. 581-603 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Over the past decades, intravital microscopy (IVM), the imaging of cells in living organisms, has become a valuable tool for studying the molecular determinants of lymphocyte trafficking. Recent advances in microscopy now make it possible to image cell migration and cell-cell interactions in vivo deep within intact tissues. Here, we summarize the principal techniques that are currently used in IVM, discuss options and tools for fluorescence-based visualization of lymphocytes in microvessels and tissues, and describe IVM models used to explore lymphoid and non-lymphoid organs. The latter will be introduced according to the physiologic itinerary of developing and differentiating T and B lymphocytes as they traffic through the body, beginning with their development in bone marrow and thymus and continuing with their migration to secondary lymphoid organs and peripheral tissues.
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  • 6
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 21 (2005), S. 411-434 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Centrosomes, spindle pole bodies, and related structures in other organisms are a morphologically diverse group of organelles that share a common ability to nucleate and organize microtubules and are thus referred to as microtubule organizing centers or MTOCs. Features associated with MTOCs include organization of mitotic spindles, formation of primary cilia, progression through cytokinesis, and self-duplication once per cell cycle. Centrosomes bind more than 100 regulatory proteins, whose identities suggest roles in a multitude of cellular functions. In fact, recent work has shown that MTOCs are required for several regulatory functions including cell cycle transitions, cellular responses to stress, and organization of signal transduction pathways. These new liaisons between MTOCs and cellular regulation are the focus of this review. Elucidation of these and other previously unappreciated centrosome functions promises to yield exciting scientific discovery for some time to come.
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  • 7
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 21 (2005), S. 695-718 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The combined use of the new technologies of multiphoton-based intravital imaging, the chemotaxis-mediated collection of invasive cells, and high sensitivity expression profiling has allowed the correlation of the behavior of invasive tumor cells in vivo with their gene expression patterns. New insights have resulted including a gene expression signature for invasive cells and the tumor microenvironment invasion model. This model proposes that tumor invasion and metastasis can be studied as a problem resembling normal morphogenesis. We discuss how these new insights may lead to a better understanding of the molecular basis of the invasive behavior of tumor cells in vivo, which may result in new strategies for the diagnosis and treatment of metastasis.
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  • 8
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 21 (2005), S. 435-456 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Secretory and transmembrane proteins enter the secretory pathway through the protein-conducting Sec61 channel in the membrane of the endoplasmic reticulum. In the endoplasmic reticulum, proteins fold, are frequently covalently modified, and oligomerize before they are packaged into transport vesicles that shuttle them to the Golgi complex. Proteins that misfold in the endoplasmic reticulum are selectively transported back across the endoplasmic reticulum membrane to the cytosol for degradation by proteasomes. Depending on the topology of the defect in the protein, cytosolic or lumenal chaperones are involved in its targeting to degradation. The export channel for misfolded proteins is likely also formed by Sec61p. Export may be powered by AAA-ATPases of the proteasome 19S regulatory particle or Cdc48p/p97. Exported proteins are frequently ubiquitylated prior to degradation and are escorted to the proteasome by polyubiquitin-binding proteins.
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  • 9
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 21 (2005), S. 511-527 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Phagocytosis, the process by which cells engulf large particles, requires a substantial contribution of membranes. Recent studies have revealed that intracellular compartments, including endocytic organelles and the endoplasmic reticulum (ER), can engage in fusion events with the plasma membrane at the sites of nascent phagosomes. The finding that ER proteins are delivered to phagosomes, where degraded peptides are loaded onto major histocompatibility complex (MHC) class II molecules, has significantly enhanced our understanding of the immune functions associated with these organelles. Although it is well known that pathogens are killed in phagosomes, the contribution of ER proteins to phagosomes has provided a novel pathway for the loading of exogenous peptides onto MHC class I molecules, a process known as cross-presentation. Thus, phagocytosis has evolved from a nutritional function in unicellular organisms to play key roles in both innate and adaptive immunity in vertebrates.
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  • 10
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 21 (2005), S. 551-580 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The sensory and motor components of nervous systems are connected topographically and contain neural maps of the external world. The paradigm for such maps is the precisely ordered wiring of the output cells of the eye to their synaptic targets in the tectum of the midbrain. The retinotectal map is organized in development through the graded activity of Eph receptor tyrosine kinases and their ephrin ligands. These signaling proteins are arrayed in complementary expression gradients along the orthogonal axes of the retina and tectum, and provide both input and recipient cells with Cartesian coordinates that specify their location. Molecular genetic studies in the mouse indicate that these coordinates are interpreted in the context of neuronal competition for termination sites in the tectum. They further suggest that order in the retinotectal map is determined by ratiometric rather than absolute difference comparisons in Eph signaling along the temporal-nasal and dorsal-ventral axes of the eye.
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  • 11
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 21 (2005), S. 271-295 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The cytoskeleton plays important roles in plant cell shape determination by influencing the patterns in which cell wall materials are deposited. Cortical microtubules are thought to orient the direction of cell expansion primarily via their influence on the deposition of cellulose into the wall, although the precise nature of the microtubule-cellulose relationship remains unclear. In both tip-growing and diffusely growing cell types, F-actin promotes growth and also contributes to the spatial regulation of growth. F-actin has been proposed to play a variety of roles in the regulation of secretion in expanding cells, but its functions in cell growth control are not well understood. Recent work highlighted in this review on the morphogenesis of selected cell types has yielded substantial new insights into mechanisms governing the dynamics and organization of cytoskeletal filaments in expanding plant cells and how microtubules and F-actin interact to direct patterns of cell growth. Nevertheless, many important questions remain to be answered.
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  • 12
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 21 (2005), S. 485-509 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The establishment of the Angiosperm root apical meristem is dependent on the specification of a stem cell niche and the subsequent development of the quiescent center at the presumptive root pole. Distribution of auxin and the establishment of auxin maxima are early formative steps in niche specification that depend on the expression and distribution of auxin carriers. Auxin specifies stem cell niche formation by directly and indirectly affecting gene activities. Part of the indirect regulation by auxin may involve changes in redox, favoring local, oxidized microenvironments. Formation of a QC is required for root meristem development and elaboration. Many signals likely pass between the QC and the adjacent root meristem tissues. Disappearance of the QC is associated with roots becoming determinate. Given the many auxin feedback loops, we hypothesize that roots evolved as part of an auxin homeostasis mechanism.
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  • 13
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 155-176 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Polarization is a feature common to many cell types. Epithelial cells, for example, exhibit a characteristic apical-basolateral polarity that is critical for their function. In addition to this ubiquitous form of polarity, whole fields of cells are often polarized in a plane perpendicular to the apical-basal axis. This form of polarity, referred to as planar cell polarity (PCP), exists in all adult Drosophila cuticular tissues, as well as in numerous vertebrate tissues, including the mammalian skin and inner ear epithelia. Recent advances in the study of PCP establishment are beginning to unravel the molecular mechanisms underlying this cellular process. This review discusses new developments in the molecular understanding of PCP in Drosophila and vertebrates and integrates the current data in a model to illustrate how interactions between PCP factors might function to generate planar polarity.
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  • 14
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 21 (2005), S. 633-657 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: In contrast to other tissues, the nervous system is enriched in the polyunsaturated fatty acids (PUFAs): arachidonic acid (AA, 20:4 n-6) and docosahexaenoic acid (DHA, 22:6 n-3). Despite their abundance in the nervous system, AA and DHA cannot be synthesized de novo by mammals; they, or their precursors, must be ingested from dietary sources and transported to the brain. During late gestation and the early postnatal period, neurodevelopment is exceptionally rapid, and substantial amounts of PUFAs, especially DHA, are critical to ensure neurite outgrowth as well as proper brain and retina development. Here, we review the various functions of DHA in the nervous system, the proteins involved in its internalization and metabolism into phospholipids, and its relationship to several neurological disorders, including Alzheimer's disease and depression.
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  • 15
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 21 (2005), S. 319-346 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Bacteria communicate with one another using chemical signal molecules. As in higher organisms, the information supplied by these molecules is critical for synchronizing the activities of large groups of cells. In bacteria, chemical communication involves producing, releasing, detecting, and responding to small hormone-like molecules termed autoinducers . This process, termed quorum sensing, allows bacteria to monitor the environment for other bacteria and to alter behavior on a population-wide scale in response to changes in the number and/or species present in a community. Most quorum-sensing-controlled processes are unproductive when undertaken by an individual bacterium acting alone but become beneficial when carried out simultaneously by a large number of cells. Thus, quorum sensing confuses the distinction between prokaryotes and eukaryotes because it enables bacteria to act as multicellular organisms. This review focuses on the architectures of bacterial chemical communication networks; how chemical information is integrated, processed, and transduced to control gene expression; how intra- and interspecies cell-cell communication is accomplished; and the intriguing possibility of prokaryote-eukaryote cross-communication.
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  • 16
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 21 (2005), S. 177-201 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Brassinosteroids (BRs), the polyhydroxylated steroid hormones of plants, regulate the growth and differentiation of plants throughout their life cycle. Over the past several years, genetic and biochemical approaches have yielded great progress in understanding BR signaling. Unlike their animal counterparts, BRs are perceived at the plasma membrane by direct binding to the extracellular domain of the BRI1 receptor S/T kinase. BR perception initiates a signaling cascade, acting through a GSK3 kinase, BIN2, and the BSU1 phosphatase, which in turn modulates the phosphorylation state and stability of the nuclear transcription factors BES1 and BZR1. Microarray technology has been used extensively to provide a global view of BR genomic effects, as well as a specific set of target genes for BES1 and BZR1. These gene products thus provide a framework for how BRs regulate the growth of plants.
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  • 17
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 21 (2005), S. 381-410 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: ʼ̛?‚ heterodimeric integrins mediate dynamic adhesive cell-cell and cell-extracellular matrix (ECM) interactions in metazoa that are critical in growth and development, hemostasis, and host defense. A central feature of these receptors is their capacity to change rapidly and reversibly their adhesive functions by modulating their ligand-binding affinity. This is normally achieved through interactions of the short cytoplasmic integrin tails with intracellular proteins, which trigger restructuring of the ligand-binding site through long-range conformational changes in the ectodomain. Ligand binding in turn elicits conformational changes that are transmitted back to the cell to regulate diverse responses. The publication of the integrin ʼ̛V?‚3 crystal structure has provided the context for interpreting decades-old biochemical studies. Newer NMR, crystallographic, and EM data, reviewed here, are providing a better picture of the dynamic integrin structure and the allosteric changes that guide its diverse functions.
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  • 18
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 105-131 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: This review surveys what is known about the structure and function of the subnuclear domains called Cajal bodies (CBs). The major focus is on CBs in mammalian cells but we provide an overview of homologous CB structures in other organisms. We discuss the protein and RNA components of CBs, including factors recently found to associate in a cell cycle-dependent fashion or under specific metabolic or stress conditions. We also consider the dynamic properties of both CBs and their molecular components, based largely on recent data obtained thanks to the advent of improved in vivo detection and imaging methods. We discuss how these data contribute to an understanding of CB functions and highlight major questions that remain to be answered. Finally, we consider the interesting links that have emerged between CBs and alterations in nuclear structure apparent in a range of human pathologies, including cancer and inherited neurodegenerative diseases. We speculate on the relationship between CB function and molecular disease.
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  • 19
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 57-79 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Phosphoinositide phosphates (PIPs) correspond to phosphorylated derivatives of phosphatidylinositol (PI). Despite their relatively low abundance in the plasma membrane, PIPs play a crucial role as precursors of second messengers and are themselves important signaling and targeting molecules. Indeed, modulation of levels of PIPs affects, for example, cortical actin organization, membrane dynamics, and cell migration. The focus of this review is on selected interesting targets of PIPs. Those proteins that bind PIPs and are involved in regulation of actin assembly, actin membrane linkage, and actin contractility are discussed, as well as those that are involved in signaling, such as small GTPases, protein kinases, and phosphatases, or in regulation of membrane dynamics.
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  • 20
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 223-245 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: In eukaryotes, the entwined pathways of RNA transport and local translational regulation are key determinants in the spatio-temporal articulation of gene expression. One of the main advantages of this mechanism over transcriptional control in the nucleus lies in the fact that it endows local sites with independent decision-making authority, a consideration that is of particular relevance in cells with complex cellular architecture such as neurons. Localized RNAs typically contain codes, expressed within cis-acting elements, that specify subcellular targeting. Such codes are recognized by trans-acting factors, adaptors that mediate translocation along cytoskeletal elements by molecular motors. Most transported mRNAs are assumed translationally dormant while en route. In some cell types, especially in neurons, it is considered crucial that translation remains repressed after arrival at the destination site (e.g., a postsynaptic microdomain) until an appropriate activation signal is received. Several candidate mechanisms have been suggested to participate in the local implementation of translational repression and activation, and such mechanisms may target translation at the level of initiation and/or elongation. Recent data indicate that untranslated RNAs may play important roles in the local control of translation.
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  • 21
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Five human teratoma cell lines have been characterized for the presence of a certain number of marker antigens whose presence or absence has been shown to be characteristic of mouse embryonal carcinoma (EC) cells. Four out of the five lines have been shown to respond to at least some of the criteria associated with murine EC cells even though only limited in vitro differentiation could be demonstrated. The significance of certain unusual marker antigen combinations present on the cell line Tera I and its clones and so far unobserved for the murine model is discussed. The observation in Tera I populations of cells carrying simultaneously both the F9 and β2-microglobulin or HLA antigens, suggest that the human cell lines may represent a novel material for the study of mammalian differentiation.
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  • 22
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 8 (1981), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Principles of Gene Manipulation. Studies in Microbiology
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  • 23
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    International journal of immunogenetics 7 (1980), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: A healthy 22-year-old woman was noted to have erythrocytes of the Pk phenotype: a strong Pk antigen, no detectable P antigen and anti-P antibody in her serum. Her erythrocytes contained four to six times as much Pk glycolipid (globotriaosylceramide or CTH) and approximately half as much P glycolipid (globotertraosylceramide or globoside) as normal red cells. The structures of CTH and globoside were characterized by analysis of permethylated sugars and complement fixation in addition to chromaographic mobility and sugar composition. Inasmuch as the erythrocytes of two Pk individuals that were analysed previously (Marcus et al., 1976) contained no detectable globoside, these abnormalities appear o represent a new phenotype in the P blood group system.
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  • 24
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 7 (1980), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: We studied 201 unrelated French Basque individuals for HLA and Bf polymorphisms. The haplotypes of eighty-seven of them were deduced from family studies. The results show the frequency of the Bf F1 allele (0.1393) which is the highest one currently reported. They confirm the high frequencies of HLA-Aw19.2 and B18 previously reported in that population and show that a whole haplotype with strong linkage disequilibria, namely Aw19.2, Cw5, B18, Bf F1, DRw3 is frequent. On the other hand, the gene frequency of Bf S is decreased (0.5497) as compared with the other European Caucasoïd populations, while a slight increase in the Bf F gene frequency (0.2960) appears. These results point out that it is of importance to consider the genetic background in choosing the population where linkage disequilibria are to be studied.
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  • 25
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 7 (1980), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The genetic control of hybrid resistance to BALB/c fibrosarcoma Meth-A was investigated. A Meth-A tumour grew slower in (BALB/c X C57BL/6)F1 and reciprocal hybrid mice than in syngeneic BALB/c mice and was also found to grow slower in females than in males. Significant F1 resistance was demonstrated after both subcutaneous and intraperitoneal injection of tumour cells. However, (BALB/c X DBA/2)F1 mice did not show any significant resistance to Meth-A. In H-2 linkage studies of [BALB/c X (BALB/c X C57BL/6)] backcross mice, no statistically significant differences in the resistance of H-2 heterozygotes and homozygotes to Meth-A were observed. These results indicated that F1 hybrid resistance to Meth-A was controlled by non-H-2-linked resistance factor(s). No linkage was observed between resistance to Meth-A and coat colour c- and b-loci.
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  • 26
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 7 (1980), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: CBA/N mice have an X-linked B cell defect which prevents them from responding to non-mitogenic thymic independent (TI-II) antigens such as dinitrophenylated (DNP-AGG) Ficoll. The F1 male progeny of CBA/N female mice express the same defect. Spleen cell suspensions from such defective mice (CBA/N X C3H/HeN F1 males) could not respond to DNP-AGG-Ficoll following in vitro immunization and subsequent transfer into irradiated, syngeneic, F1 male recipients as expected. In contrast, normal CBA/N X C3H/HeN F1 female spleen cells could respond and effect a ‘rescue'; they mounted strong plaque-foriming cell 7 days after in vitro exposure to DNP-AGG-Ficoll and subsequent transfer into irradiated F1 male recipients. Defective F1 male spleen cells could bind significant quantities of DNP-AGG-Ficoll, however, after, in vitro exposure. Extensive washing of these spleen cells could not reverse this binding. Such DNP-AGG-Ficoll-exposed and washed F1 male spleen cells could, after transfer, aid normal untreated F1 female cells in their rescue function. The defective F1 male spleen cells could convey immunogenic quantities of DNP-AGG-Ficoll to the ‘rescuing’ F1 female cells.Mitomycin treatment of F1 male cells did not interfere with their conveyor function. Goat anti-mouse μ serum impeded the passive antigen conveyor function of defective F1 male cells as did prior exposure to high concentrations of free DNP-AGG hapten. Our data support the view that the B cell defect of CBA/N X C3H/HeN F1 male mice does not relate to antigen binding, but rather to an inability to be effectively triggered by certain cell-bound polymeric antigens.
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  • 27
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 7 (1980), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
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  • 28
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 7 (1980), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Results of a population study with all currently available B-cell specific alloantisera indicate that eight antigens controlled by the RhLA-linked DR locus can now be identified. This leaves a gene frequency of about 0.15 for unidentified or ‘blank’ antigens of that locus. Of the nine identifiable la antigens which are not controlled by the DR locus, three or four may form the basis of a second series which is probably also controlled by the RhLA region.
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    International journal of immunogenetics 7 (1980), S. 0 
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    Notes: Induction of tolerance to bovine serum albumin was studied in mice selected for high (H) or low (L) antibody responsiveness and in their F1 hybrids. No high or low zone tolerances were obtained in H mice whereas L mice were susceptible to tolerance induction by the two schedules. H mice were immunized by repeated injections of tolerogenic BSA for low zone tolerance induction but not after the administration of a single high dose of tolerogenic BSA. Resistance to tolerance induction is dominant in F1 hybrids.
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  • 30
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    International journal of immunogenetics 7 (1980), S. 0 
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    Notes: An attempt is made to account for immunoglobulin chain synthesis in terms of genetic events involving IS or controlling elements analogous to those found in bacteria, maize and drosophila. Transposition of variable and constant genes and normal immunoglobulin chain synthesis as well as qualitative and quantitative abnormalities might be explained by such regulatory elements. Intrachromosomal transpositions over short distances would be expressed as apparent hypermutability or redundancy of the variable DNA segment. The constant gene might comprise four sequences coding for the three homology domains and the hinge, separated by intervening sequences. A strong preference for shortrange transposition on the same chromosome and immobilization of the controlling element in the end might account for allelic exclusion.
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  • 31
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    International journal of immunogenetics 7 (1980), S. 0 
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    Notes: Fab2 fragments from antisera raised in rabbits with partially purified cellular and serum HLA antigens were tested for their ability to block the cytolytic activity of operationally specific HLA-A, B alloantisera. One Fab2 fragment preparation blocked the cytolytic activity of all the HLA-A,B alloantisera tested; the remaining nine inhibited the lytic activity of alloantisera to certain HLA-A,B allospecificities, suggesting that these xenoantisera contain antibody to certain HLA-A,B allotype determinants or to closely associated structures. In contrast to previous reports in the literature none of the xenoantisera contained significant amounts of antibodies to human β2-microglobulin.
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  • 32
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    International journal of immunogenetics 11 (1984), S. 0 
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    Notes: NIM-M8 is a monoclonla IgM antibody, specific for the LWab antigen as shown by its reaction with red cells of all donors except those lacking LWa, LWb and LWab. Indirect immunofluorescent staining and cell sorter analyses have shown that LWab is present on a subpopulation of human lymphoctes. Cell fractionation studies indicate that subsets of both B and T cells express LWab and it may, therefore, provide a further marker for heterogeneity in these lymphocyte populations.
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  • 33
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    Notes: Immunoprecipitation using a monoclonal antibody showed that the Wrb antigen is present on the abnormal (δ-α) hybrid sialoglycoprotein of Sta-positive human erythrocytes but not on the abnormal (δ-α) hybrid sialoglycoprotein of Dantu-positive erythrocytes. These results provide further information regarding the nature and location of the Wrb antigen on the normal erythrocyte sialoglycoprotein α.
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  • 34
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    International journal of immunogenetics 11 (1984), S. 0 
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    Notes: We studied structural and functional characteristics of lymphocytes from adult and fetal baboons (Papio cynocephalus). Flow cytometry with monoclonal antibodies to human lymphocyte antigens and plant lectins was used to define expression of surface antigens on lymphocytes from adult and 140 day fetal baboons (term = 180 days). Major T cell antigenic determinants on adult and fetal baboon lymphocytes were the Tp50, Tp32-45, and p45 glycoproteins detected by monoclonal reagents T11, OKT8, and OKT10 respectively. Baboon T lymphocytes did not react with the OKT3/anti-Leu4 or OKT4/ anti-Leu3a reagents which detect, respectively, Tp19-29 and Tp55, major surface glycoproteins on human T lymphocytes. OKT6, which identifies the human TL antigen equivalent on thymocytes, did not react with baboon thymocytes. These data demonstrate major evolutionary divergence between human and baboon T lymphocytes. By contrast, baboon lymphocytes resembled human peripheral lymphocytes in reactivities with several non-T cell reagents. Lectin binding studies revealed substantially fewer peanut agglutinin-and wheat germ agglutinin-binding cells in suspensions of baboon fetal splenocytes and adult peripheral lymphocytes compared with fetal thymocytes. Thereffore, maturation of baboon T lymphocytes is associated with loss of surface carbohydrate structures that bind these lectins. Adult and fetal baboon lymphocytes resembled human and murine lymphocytes in their capabilities to respond to mitogens and to produce interleukin-2. As in oter species, adult, but not fetal baboon lymphocytes, mediated NK activity against a variety of nucleated target cells. Despite divergence in lymphocyte antigen epression, babbon lymphocyte functional development colsely parallels that seen in humans.
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  • 35
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    International journal of immunogenetics 11 (1984), S. 0 
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    Notes: The Gm, Am and Km immunoglobulin allotypes and ABO blood groups were studied in three groups of Tunisian Berbers.The results showed that the actual Berbers of Tunisia present certain heterogeneity and their ancestors were probably the first inhabitants of North Africa. Indeed, although their Gm-Am haplotypes are mainly Caucasoid, some of them are typically African.The group of Kesra village, the most Caucasoid, shows frequencies of Gm-Am haplotypes very close to those of South European populations, particularly the Spanish, who are probably of the same origin. The gene frequencies of the ABO groups in the three Berber groups were similar to those recorded in European populations with a relatively high frequency of the O genes typical of the Berbers.
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  • 36
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    International journal of immunogenetics 11 (1984), S. 0 
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    Notes: Monoclonal antibody 212.i.4.2 mediated complement-dependent lysis of spleen and lymph node cells carrying the tw1, tw12, tw71, t6, tw73, and tLub1 haplotypes, while cells from mice carrying 11 other t haplotypes were not lysed. The antibody also detected an epitope controlled by genes in the H-2Dd region of non-t mice. A molecule of 46,000 molecular weight was immunoprecipitated by 212.i.4.2 from detergent extracts of 125I-labelled spleen cells of +/tw12 and B10.D2 mice. The H-2dm2 mutation did not alter the expression of the epitope recognized by 212.i.4.2. However, the H-2dm1 mutation decreased the reactivity of lymphoid cells with the antibody in cytotoxicity tests, and 212.i.4.2 immunoprecipitated little or no protein from extracts of B10.D2(R106) spleen cells which carry the H-2dm1 mutation.
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  • 37
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    International journal of immunogenetics 11 (1984), S. 0 
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    Notes: Spleen cells from Balb/c mice given multiple injections of intact human erythrocytes (group O, NN) were fused with NS1 myeloma cells. Culture fluids from the resulting hybrid cells were screened for agglutinating antibody against a panel of erythrocytes. One cell line, 2/23, secreted an IgM antibody which reacted more strongly with NN than with MM cells. Neuraminidase or papain treatment of erythrocytes abolished agglutination whereas trypsin treatment did not. Reactions with U-erythrocytes of different MN phenotypes confirmed the anti-N specificity of monoclonal antibody 2/23. This is the first report of monoclonal anti-N stimulated by the immunization of mice with intact erythrocytes.
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  • 38
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    International journal of immunogenetics 11 (1984), S. 0 
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    Notes: Spleen cells from 30 individual murine irradiation chimeras of the type (P1 x P2)F1→ P1 were compared in a rosetting assay for H-2K and H-2D cell surface antigen expression with normal (P1 x P2)F1 hybrid controls. Eleven out of the 30 chimeras were in the normal range, but the other 19 differed from F1 controls by 4- to 100-fold in endpoint titre for at least one H-2K or H-2D antigen. Every possible class of variation was found, i.e. up or down variation of H-2K or H-2D antigens of P1 or P2 type. This evidence, together with data from T6 chromosome marker experiments which also showed full reconstitution of lethally irradiated P1 recipients by (P1 x P2)F1 donor lymphomyloid stem cells, suggested that incomplete reconstitution was not the cause of H-2 antigenic variation.Low expression of P2 H-2 antigens on spleen cells derived from (P1 x P2)F1→ P1 chimeras was investigated further. Fifteen lethally irradiated (P1 x P2)F1 recipients of bone marrow cells from two such chimeras were all of normal F1 H-2 phenotype when tested 10-12 weeks after reconstitution, thus excluding stable, low P2 H-2-expressing variant F1 stem cells as a cause of the phenomenon. If P1 recipients were hyperimmunized against P2 cells before lethal irradiation and reconstitution with (P1 x P2)F1 stem cells, there were significantly fewer Till-McCulloch colonies in their spleens 10 days after reconstitution than in spleens of unimmunized controls. Also 〉 90% of immunized recients died by 6 weeks after stem cell injection but two survivors both showed very low levels of P2 H-2K and H-2D antigens. These results together with previously published evidence of anti-P2 Tc cell activity and P2 skin graft rejection in (P1 x P2)F1→ P1 chimeras suggested that residual anti-P2 immunological capability in lethally irradiated P1 recipients may be associated with low P2 H-2 expression on their F1-derived spleen cells, although the mechanism does not involve selection of stable, variant F1 stem cells. The mechanism(s) of other classes of variation in H-2 expression in (P1 x P2)F1→ P1 chimeras were not investigated.
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    International journal of immunogenetics 11 (1984), S. 0 
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    Notes: RNA was extracted from the splenocytes of Brucella abortus antigen stimulated mice and of control mice. The proportion of chromatographically separated polyadenylated 11.2S mRNA, was determined. With the technique used, only stimulated mice exhibited significant amounts of this RNA species. The highest level was reached 1 day after the stimulation, and the decay from this level presented an oscillatory form during the 4 weeks following the injection.In two different genetic backgrounds, H-2b mice did not respond to the stimulus, in contrast to H-2a and H-2f mice. H-2b/H-2f heterozygotes behaved roughly as intermediate between H-2b and H-2f mice. This genetic control seems to parallel the genetic control of some Brucella-induced, thymus-dependent events previously described.
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    Notes: Book Reviews in this ArticleR. WITKOWSKI and O. PROKOP: Genetik erblicher Syndrome und Mgbildungen. Worterbuch fur die Familienberatung.
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  • 41
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    International journal of immunogenetics 11 (1984), S. 0 
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    Notes: Monoclonal anti-Ia inhibition experiments were conducted to confirm and extend genetic mapping data of I-A gene control of immunity to human haemoglobin (Hb). It was found that the Aβ gene is of critical importance in conferring immunity to the α-chain and β-chain subunits of Hb. A possible involvement of I-E region genes in B10.D2 mice to β-chain is discussed. Through the use of an α-chain specific T cell clone data, is obtained indicating that an intact Ia.8+ Aβ chain is necessary for antigen presentation in vitro.
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  • 42
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    International journal of immunogenetics 10 (1983), S. 0 
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    Notes: C4 is composed of two tightly linked genes (C4A and C4B) lying within the major histocompatibility complex of chromosome 6 that can be demonstrated by agarose gel electrophoresis. Seven alleles and five alleles at the C4A and C4B loci, respectively, were detected in 169 black individuals from the southeastern United States. Furthermore, the phenotypic frequencies of C4A6, C4A5, C4A4, C4B4, C4B3, and C4BQO were significantly different between black and white Americans.
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  • 43
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    International journal of immunogenetics 10 (1983), S. 0 
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    Notes: Two B complex genotypes, B1B1 and B19B19, of outbred line S1, were tested for low and high immune response to GAT, from which four recombinants were recovered: B1B1 GAT-hi and lo, and B19B19 GAT-hi and -lo. Also included in the study were birds of B2B2 genotype with an intermediate level of immune response to GAT.A total of 225 birds of these groups were challenged with the Bryan strain of Rous Sarcoma virus subgroup C, RSV (RAV-7), by inoculation into the wing web at five weeks of age. The B1B1 genotype had the lowest percentage of regressors (17.6%), B19B19 had the highest (42.2%), and the B2B2 genotype was intermediate (23.7%). Combining the results of GAT response over the B1B1 and B19B19 genotypes, 14.0% of GAT-lo and 37.8% of GAT-hi regressed their tumours, respectively. The highly significant (P ≤ 0.01) difference between the combined GAT-hi and -lo groups would suggest that the Rs locus controlling tumour regression induced by the subgroup C virus is closely linked to the region controlling immune response to GAT, but the data also provides evidence that the B-F region of the B complex also plays an important role in RSV-induced tumour regression.
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  • 44
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    International journal of immunogenetics 10 (1983), S. 0 
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    Notes: Surface immunoglobulin on spleen cells from NZB and NZB/W mice and congenic mice bearing the nude or X-linked immune defective (Xid) gene was examined by flow microfluorometry with regard to both the frequency of positive cells and density expressed on the cell. These data indicate that although the frequency of unseparated sIg+ B lymphocytes is equivalent among all of these groups of mice, the densities of sIgM and sIgD are different. Spleen cells from these mice were also separated by free-flow electrophoresis and analyzed in a similar manner. This analysis demonstrated the absence of a subpopulation of B lymphocytes with a low electrophoretic mobility and low expression of sIgM. These studies suggest that maturational and/or activation states of the B cells in mice bearing the Xid or nude genes are different from those seen in the parent strains of mice. Such alterations in cell-surface antigens correlate with differences in the natural history of immunopathology of the autoimmune disease in these congenic colonies of New Zealand mice.
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    International journal of immunogenetics 10 (1983), S. 0 
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    Notes: Fifty-five Caucasoid patients with polymalgia rheumatica (PMR) or giant cell arteritis (GCA) were immunoglobulin (Gm) allotyped for this study. Forty-four of these patients had been previously HLA-A,B,C and DR locus allotyped. The incidence of the immunoglobulin allotypic marker Glm(2) was significantly increased in the GCA group (50.00% v. controls 18.75%, P= 〈0.01). There was a similar but insignificant rise of this Gm marker in the PMR group (27.24% v. 18.75%, NS). The increase in Glm(2) in the GCA group was not accompanied by a corresponding rise in the number of people homozygous for Glm(2), i.e., all the increase could be attributed to patients with the Glm(1,2,3): G3m(5,10,21) phenotype.
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  • 46
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    Notes: The strains B 10.S(7R), B 10.S(23 R) and B 10.S(24R), all thought to be genetically identical, differ in levels of susceptibility to infection with Trichinella spiralis. In a series of nine independent experiments, B 10.S(7R) was shown to be more susceptible than the other two strains. In another series of seven experiments, the strain B 10.A(18R) was shown to be more susceptible to infection with T. spiralis than the strains B 10.S(21R) or B 10.BAR-5, all of which were thought to share common H-2 alleles. These results indicate that a gene mapping between the S and D loci influences susceptibility to infection with T. spiralis. Typing of these strains for Qa and Tl loci rule out the possibility of a double crossover accounting for the differences observed. The new gene is designated Ts-2. Previously published data have also been reinterpreted and another gene Ts-1 is shown to be associated with the Aβ locus. When the d allele is expressed at the Ts-2 locus, strains of mice expressing s, q, f or b alleles at Ts-1 are rendered more susceptible to infection.
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  • 47
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    Notes: IgG and IgA heavy chain allotypes were determined in the sera of 483 Caucasian Type 1 diabetes patients and 503 Caucasian healthy controls. There was no significant difference between patients and controls neither on the level of Gm phenotype frequencies nor on the level of Gm three-locus and two-locus haplotype frequencies. A selective IgA deficiency was found in 14 patients (2.9%) but in none of the control individuals (P〈10-4).
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    Notes: Gm allotypes were detected and quantitated by radioimmunoassay (RIA) in paired serum and CSF samples from patients suffering from various neurological diseases. Of 115 patients with neurological disorders (65 MS and 50 others), seven subjects displayed one or two allotypes in their CSF which were absent in serum. The Gm phenotype in the patient's serum allowed us to infer the genotype without the need of familial data. A comparison of the regression curves obtained in RIA from the unexpected allotype in CSF and the counterpart in a normal serum pool argued for an identity of the Gm antigen carried by both inhibitory molecules. The unexpected allotype(s) in CSF can be considered as the product of a latent Gm gene which may be activated by either immune perturbations due to the disease per se or some particular immune regulations in the central nervous system.
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    Notes: Book reviewed in this article:N. Catsimpoolas; Cell Analysis. Plenum Publishing CorpJ.W.Shay: Techniques In Somatic Cell Genetics
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    Notes: Immunoprecipitaon studies of the rhesus monkey major histocompatibility system have shown that the RhLA-DR locus codes for class II antigens with molecular features that are homologous to the class II antigens coded for by the human HLA-dR locus, The products of another alloantigenic RhLA-linked locus of the rhesus monkey, called ‘48’, is provisionally characterized as a class I system.
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    Notes: The relationships between the antigens recognized by four monoclonal anti-human ‘Ia’-like antibodies were investigated using sequential immunoprecipitation and capping techniques. Two of the antibodies were ‘monomorphic’ and have previously been shown to recognize epitopes in which carbohydrate residues are involved, whereas the two ‘polymorphic’ antibodies recognized protein-defined epitopes—one of these epitopes being present on MB+DR- molecules. In the absence of an indisputable anti-DR monoclonal antibody, it was not possible to conclusively verify which ‘Ia’-encoded antigens were detected by the anti-‘Ia’-like monoclonal antibodies. Nevertheless, several firm conclusions could be drawn: (a) so-called ‘monomorphic’ antibodies do not necessarily react with all ‘Ia’ molecules encoded by a single locus—from the results using the two monomorphic antibodies, B5.1 and 3F1.1, described herein, two populations of antigens being B5.1+3F1.1+ and B5.1+3F1.1- were identified; (b) cross-reactivity of a polymorphic determinant expressed on antigenically-separable ‘Ia’ molecules was noted—using the two polymorphic antibodies, 26.1 and F5C9, molecules which were 26.1+F5C9+ and 26.1-F5C9+ were identified; and (c) the data clearly point to the existence of at least two loci coding for ‘Ia’-like antigens (one of which may or may not be the HLA-DR locus). Given that polymorphisms can now include protein- and carbohydrate-defined epitopes, that cross-reactions occur and that the definition of DR itself by monoclonal antibodies is not clear, the complexity of the human ‘Ia’ antgens is apparent.
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    Notes: We report HLA genotypes in four familial cases of Hodgkin's disease (HD), Nodular Sclerosis (NS) histological subtype, where all patients showed B18 antigen. This finding, although statistically not supported, confirms the possible correlation between HD and B18 antigen which carries a high relative risk in international data.
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    Notes: Previous studies from this laboratory have resulted in the determination of the antigenic structure of sperm-whale myoglobin (Mb). In the present work, we have investigated the fine specificity requirements for T-cell recognition of one of the Mb antigenic sites (antigenic site 5). The antigenic site (peptide 145-153) and seven progressively longer peptides, increasing in length stepwise by two residues at a time, up to 22 residues in length (peptide 132-153), were synthesized. In addition, four truncated peptides were synthesized with intentional deletions at Tyr- 151 and Ala- 144. The T-cell recognition of these purified synthetic peptides was examined here in detail in three strains of mice (BALB/cByJ, B10.D2/n and SJL/J). Mb-primed mice afforded T-cells which proliferated to smaller peptides (two or four residues longer than the site; i.e. peptides 145-153 and 143-153) and more so to the longer peptides 135-153 and 132-153 and to Mb. No response was obtained to the truncated peptides, thus underscoring the fine specificity T-cells. No response was obtained also to intermediate-sized peptides. The latter result, due to an unfavourable mode of folding, suggested a conformational dependency in T-lymphocyte recognition.
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    Notes: Serum blood samples from 563 of the total 700 Nganasans, members of the isolate in the northern-most part of Siberia were tested for G1m, (z,a,x,f), G2m (n), G3m (g,b0,b1,b3,b5,s,t), and km (1) allotypic determinants. Additionally, 78 Yenisey Samoyeds (Entsi) who are the Nganasan's western neighbours were studied. Both populations are remarkable for high frequency of ‘Northern Oriental’Gm (za;.;b0b3b5st) which appears to be the most frequent haplotype in the Nganasans (0.486), and is the second frequent in Yenisey Samoyeds (0.276). The Gm (f;b) generalized haplotype which used to be considered as an indicator of Caucasian gene flow occurred in the Nganasans in the very low frequency of 0.008, versus 0.045 revealed in adjoining Yenisey Samoyeds. Both populations also differ in the frequency of Km1 which is two times lower in the Nganasans (0.048), than in Yenisey Samoyeds (0.103). When segregation ratios for the Gm locus were inspected in 67 Nganasan families, no apparent deviations from Mendelian expectations, and no recombinant phenotypes were observed.
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    International journal of immunogenetics 10 (1983), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Genetic control of PQ prolongation of the electrocardiogram (ECG) in the mouse, immunized with killed group A streptococci, was studied by using various congenic mice. Mice of H-2a, H-2k and H-2f haplotypes showed high frequencies of PQ prolongation, while haplotypes of H-2b, H-2d and H-2s showed low frequencies of PQ prolongation. Studies using various recombinant mice revealed that at least one immune-associated (Ir) gene mapped in the left side of the I-B subregion. High responsiveness of F1 hybrids of H-2b and H-2d, as well as B1O.A(5R) and B10.A(3R), suggests the existence of a complementing gene. In addition, the differences between C3H and CKB, as well as differences between C3H.SW and CWB, indicate that another Ir gene maps in the immunoglobulin heavy chain (Igh) coding loci. Repeated injections of anti-I-J or anti-I-A antisera also modified this PQ prolongation. These results suggested that both the major histocompatibility complex (MHC) and immunoglobulin (Igh) loci seem to be playing important roles in the pathogenesis of PQ prolongation.
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    International journal of immunogenetics 10 (1983), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
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    Notes: The growth and reproduction complex contains recessive genes (grc) which influence body weight and gonadal development. Homozygous males are sterile, and they have an arrest of spermatogenesis at the primary spermatocyte stage. Homozygous females are fertile but have a reduced reproductive capacity. The data presented in this paper show that the latter defect is associated with a decrease in the relative number of secondary ovarian follicles and an increase in the number of atretic follicles. This finding indicates that most of the primary follicles do not mature properly. Thus, the genetic defect in gametogenesis controlled by the grc appears to occur at the same stage of development in both females and males.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 247-269 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Approximately one percent of the human genome encodes proteins that either regulate or are regulated by direct interaction with members of the Rho family of small GTPases. Through a series of complex biochemical networks, these highly conserved molecular switches control some of the most fundamental processes of cell biology common to all eukaryotes, including morphogenesis, polarity, movement, and cell division. In the first part of this review, we present the best characterized of these biochemical pathways; in the second part, we attempt to integrate these molecular details into a biological context.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 529-550 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: The conserved protein-conducting channel, referred to as the Sec61 channel in eukaryotes or the SecY channel in eubacteria and archaea, translocates proteins across cellular membranes and integrates proteins containing hydrophobic transmembrane segments into lipid bilayers. Structural studies illustrate how the protein-conducting channel accomplishes these tasks. Three different mechanisms, each requiring a different set of channel binding partners, are employed to move polypeptide substrates: The ribosome feeds the polypeptide chain directly into the channel, a ratcheting mechanism is used by the eukaryotic endoplasmic reticulum chaperone BiP, and a pushing mechanism is utilized by the bacterial ATPase SecA. We review these translocation mechanisms, relating biochemical and genetic observations to the structures of the protein-conducting channel and its binding partners.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 35-56 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Apoptosis plays a central role in the development and homeostasis of metazoans. Research in the past two decades has led to the identification of hundreds of genes that govern the initiation, execution, and regulation of apoptosis. An earlier focus on the genetic and cell biological characterization has now been complemented by systematic biochemical and structural investigation, giving rise to an unprecedented level of clarity in many aspects of apoptosis. In this review, we focus on the molecular mechanisms of apoptosis by synthesizing available biochemical and structural information. We discuss the mechanisms of ligand binding to death receptors, actions of the Bcl-2 family of proteins, and caspase activation, inhibition, and removal of inhibition. Although an emphasis is given to the mammalian pathways, a comparative analysis is applied to related mechanistic information in Drosophila and Caenorhabditis elegans.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 347-380 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The nuclear envelope (NE) is a highly specialized membrane that delineates the eukaryotic cell nucleus. It is composed of the inner and outer nuclear membranes, nuclear pore complexes (NPCs) and, in metazoa, the lamina. The NE not only regulates the trafficking of macromolecules between nucleoplasm and cytosol but also provides anchoring sites for chromatin and the cytoskeleton. Through these interactions, the NE helps position the nucleus within the cell and chromosomes within the nucleus, thereby regulating the expression of certain genes. The NE is not static, rather it is continuously remodeled during cell division. The most dramatic example of NE reorganization occurs during mitosis in metazoa when the NE undergoes a complete cycle of disassembly and reformation. Despite the importance of the NE for eukaryotic cell life, relatively little is known about its biogenesis or many of its functions. We thus are far from understanding the molecular etiology of a diverse group of NE-associated diseases.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 605-631 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Adult tissue-specific stem cells have the capacity to self-renew and generate functional differentiated cells that replenish lost cells throughout an organism's lifetime. Studies on stem cells from diverse systems have shown that stem cell function is controlled by extracellular cues from the niche and by intrinsic genetic programs within the stem cell. Here, we review the remarkable progress recently made in research regarding the stem cell niche. We compare the differences and commonalities of different stem cell niches in Drosophila ovary/testis and Caenorhabditis elegans distal tip, as well as in mammalian bone marrow, skin/hair follicle, intestine, brain, and testis. On the basis of this comparison, we summarize the common features, structure, and functions of the stem cell niche and highlight important niche signals that are conserved from Drosophila to mammals. We hope this comparative summary defines the basic elements of the stem cell niche, providing guiding principles for identification of the niche in other systems and pointing to areas for future studies.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 659-693 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The TGF-?‚ family comprises many structurally related differentiation factors that act through a heteromeric receptor complex at the cell surface and an intracellular signal transducing Smad complex. The receptor complex consists of two type II and two type I transmembrane serine/threonine kinases. Upon phosphorylation by the receptors, Smad complexes translocate into the nucleus, where they cooperate with sequence-specific transcription factors to regulate gene expression. The vertebrate genome encodes many ligands, fewer type II and type I receptors, and only a few Smads. In contrast to the perceived simplicity of the signal transduction mechanism with few Smads, the cellular responses to TGF-?‚ ligands are complex and context dependent. This raises the question of how the specificity of the ligand-induced signaling is achieved. We review the molecular basis for the specificity and versatility of signaling by the many ligands through this conceptually simple signal transduction mechanism.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 81-103 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Sphingolipids and glycosphingolipids are membrane components of eukaryotic cell surfaces. Their constitutive degradation takes place on the surface of intra-endosomal and intra-lysosomal membrane structures. During endocytosis, these intra-lysosomal membranes are formed and prepared for digestion by a lipid-sorting process during which their cholesterol content decreases and the concentration of the negatively charged bis(monoacylglycero)phosphate (BMP)Đ??erroneously also called lysobisphosphatidic acid (LBPA)Đ??increases. Glycosphingolipid degradation requires the presence of water-soluble acid exohydrolases, sphingolipid activator proteins, and anionic phospholipids like BMP. The lysosomal degradation of sphingolipids with short hydrophilic head groups requires the presence of sphingolipid activator proteins (SAPs). These are the saposins (Saps) and the GM2 activator protein. Sphingolipid activator proteins are membrane-perturbing and lipid-binding proteins with different specificities for the bound lipid and the activated enzyme-catalyzed reaction. Their inherited deficiency leads to sphingolipid- and membrane-storage diseases. Sphingolipid activator proteins not only facilitate glycolipid digestion but also act as glycolipid transfer proteins facilitating the association of lipid antigens with immunoreceptors of the CD1 family.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 297-318 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: RNA silencing refers to a broad range of phenomena sharing the common feature that large, double-stranded RNAs or stem-loop precursors are processed to ca. 21Đ??26 nucleotide small RNAs, which then guide the cleavage of cognate RNAs, block productive translation of these RNAs, or induce methylation of specific target DNAs. Although the core mechanisms are evolutionarily conserved, epigenetic maintenance of silencing by amplification of small RNAs and the elaboration of mobile, RNA-based silencing signals occur predominantly in plants. Plant RNA silencing systems are organized into a network with shared components and overlapping functions. MicroRNAs, and probably trans-acting small RNAs, help regulate development at the posttranscriptional level. Small interfering RNAs associated with transgene- and virus-induced silencing function primarily in defending against foreign nucleic acids. Another system, which is concerned with RNA-directed methylation of DNA repeats, seems to have roles in epigenetic silencing of certain transposable elements and genes under their control.
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    Annual Review of Immunology 1 (1983), S. 87-115 
    ISSN: 0732-0582
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    Annual Review of Immunology 1 (1983), S. 143-173 
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    Annual Review of Immunology 1 (1983), S. 335-359 
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    Annual Review of Immunology 1 (1983), S. 307-327 
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    Annual Review of Immunology 1 (1983), S. 439-461 
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    Annual Review of Immunology 1 (1983), S. 529-568 
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    Annual Review of Immunology 23 (2005), S. 161-196 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Our views regarding the origins and functions of splenic marginal zone B cells have changed considerably over the past few years. Perspectives regarding the development and function of these cells vary considerably between investigators studying human and rodent immunology. Marginal zone B cells are now recognized to constitute a distinct naive B lymphoid lineage. Considerable progress has been made regarding the mechanisms involved in marginal zone B cell development in the mouse. Many of the molecular events that participate in the retention of this lineage of B cells in the marginal zone have been identified. Here, we discuss the functions of these cells in both innate and adaptive immunity. We also attempt to reconcile differing viewpoints regarding the generation and function of marginal zone B cells in rodents and primates.
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    Annual Review of Immunology 23 (2005), S. 487-513 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Helper T (Th) cellĐ??regulated B cell immunity progresses in an ordered cascade of cellular development that culminates in the production of antigen-specific memory B cells. The recognition of peptide MHC class II complexes on activated antigen-presenting cells is critical for effective Th cell selection, clonal expansion, and effector Th cell function development (Phase I). Cognate effector Th cellĐ??B cell interactions then promote the development of either short-lived plasma cells (PCs) or germinal centers (GCs) (Phase II). These GCs expand, diversify, and select high-affinity variants of antigen-specific B cells for entry into the long-lived memory B cell compartment (Phase III). Upon antigen rechallenge, memory B cells rapidly expand and differentiate into PCs under the cognate control of memory Th cells (Phase IV). We review the cellular and molecular regulators of this dynamic process with emphasis on the multiple memory B cell fates that develop in vivo.
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    Annual Review of Immunology 23 (2005), S. 415-445 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: The proliferation and differentiation of lymphocytes are regulated by receptors localized on the cell surface. Engagement of these receptors induces the activation of intracellular signaling proteins that transmit the receptor signals to distinct targets and control the cellular responses. The first signaling proteins to be discovered in higher organisms were the products of oncogenes. For example, the kinases Src and Abelson (Abl) were originally identified as oncogenes and were later characterized as important proteins for signal transduction in various cell types, including lymphocytes. Now, as many cellular signaling molecules have been discovered and ordered into certain pathways, we can better understand why particular signaling proteins are associated with tumorigenesis. In this review, we discuss recent progress in unraveling the molecular mechanisms of signaling pathways that control the proliferation and differentiation of early B cells. We point out the concepts of auto-inhibition and subcellular localization as crucial aspects in the regulation of B cell signaling.
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    Annual Review of Immunology 23 (2005), S. 683-747 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Multiple sclerosis (MS) develops in young adults with a complex predisposing genetic trait and probably requires an inciting environmental insult such as a viral infection to trigger the disease. The activation of CD4+ autoreactive T cells and their differentiation into a Th1 phenotype are a crucial events in the initial steps, and these cells are probably also important players in the long-term evolution of the disease. Damage of the target tissue, the central nervous system, is, however, most likely mediated by other components of the immune system, such as antibodies, complement, CD8+ T cells, and factors produced by innate immune cells. Perturbations in immunomodulatory networks that include Th2 cells, regulatory CD4+ T cells, NK cells, and others may in part be responsible for the relapsing-remitting or chronic progressive nature of the disease. However, an important paradigmatic shift in the study of MS has occurred in the past decade. It is now clear that MS is not just a disease of the immune system, but that factors contributed by the central nervous system are equally important and must be considered in the future.
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    Annual Review of Immunology 23 (2005), S. 651-682 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: CD8+ T cells play a critical role in antiviral immunity by exerting direct antiviral activity against infected cells. Because of their ability to recognize all types of viral proteins, they offer the promise of providing broad immunity to viruses that evade humoral immunity by varying their surface proteins. Consequently, there is considerable interest in developing vaccines that elicit effective antiviral TCD8+ responses. Generating optimal vaccines ultimately requires rational design based on detailed knowledge of how TCD8+ are activated in vivo under natural circumstances. Here we review recent progress obtained largely by in vivo studies in mice to understand the mechanistic basis for activation of naive TCD8+ in virus infections. These studies point the way to detailed understanding and provide some key information for vaccine development, although much remains to be learned to enable truly rational vaccine design.
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    Annual Review of Immunology 23 (2005), S. 945-974 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: The Notch pathway is gaining increasing recognition as a key regulator of developmental choices, differentiation, and function throughout the hematolymphoid system. Notch controls the generation of hematopoietic stem cells during embryonic development and may affect their subsequent homeostasis. Commitment to the T??cell lineage and subsequent stages of early thymopoiesis is critically regulated by Notch. Recent data indicate that Notch can also direct the differentiation and activity of peripheral T and B cells. Thus, the full spectrum of Notch effects is just beginning to be understood. In this review, we discuss this explosion of knowledge as well as current controversies and challenges in the field.
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    Annual Review of Physiology 67 (2005), S. 25-37 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Peter Hochachka was one of the most creative forces in the field of comparative physiology during the past half-century. His career was truly an exploratory adventure, in both intellectual and geographic senses. His broad comparative studies of metabolism in organisms as diverse as trout, tunas, oysters, squid, turtles, locusts, hummingbirds, seals, and humans revealed the adaptable features of enzymes and metabolic pathways that provide the biochemical bases for diverse lifestyles and environments. In its combined breadth and depth, no other corpus of work better illustrates the principle of "unity in diversity" that marks comparative physiology. Through his publications, his stimulating mentorship, his broad editorial services, and his continuousĐ??and highly infectiousĐ??enthusiasm for his field, Peter Hochachka served as one of the most influential leaders in the transformation of comparative physiology.
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    Annual Review of Physiology 67 (2005), S. 1-21 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: My scientific life has been spent trying to understand how cells communicate with each other. This interest in cell signaling began with studies on the control of fluid secretion by an insect salivary gland, and the subsequent quest led to the discovery of inositol trisphosphate (IP3) and its role in calcium signaling, which effectively divided my scientific career into two distinct parts. The first part was primarily experimental and culminated in the discovery of IP3, which set the agenda for the second half during which I have enjoyed exploring the many functions of this remarkably versatile signaling system. It has been particularly exciting to find out how this IP3/Ca2+ signaling pathway has been adapted to control processes as diverse as fertilization, proliferation, cell contraction, secretion, and information processing in neuronal cells.
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    Notes: Over the past four years RNA interference (RNAi) has exploded onto the research scene as a new approach to manipulate gene expression in mammalian systems. More recently, RNAi has garnered much interest as a potential therapeutic strategy. In this review, we briefly summarize the current understanding of RNAi biology and examine how RNAi has been used to study the genetic basis of physiological and disease processes in mammalian systems. We also explore some of the new developments in the use of RNAi for disease therapy and highlight the key challenges that currently limit its application in the laboratory, as well as in the clinical setting.
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    Annual Review of Physiology 67 (2005), S. 259-284 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: The stress response is subserved by the stress system, which is located both in the central nervous system and the periphery. The principal effectors of the stress system include corticotropin-releasing hormone (CRH); arginine vasopressin; the proopiomelanocortin-derived peptides ʼ̛-melanocyte-stimulating hormone and ?‚-endorphin, the glucocorticoids; and the catecholamines norepinephrine and epinephrine. Appropriate responsiveness of the stress system to stressors is a crucial prerequisite for a sense of well-being, adequate performance of tasks, and positive social interactions. By contrast, inappropriate responsiveness of the stress system may impair growth and development and may account for a number of endocrine, metabolic, autoimmune, and psychiatric disorders. The development and severity of these conditions primarily depend on the genetic vulnerability of the individual, the exposure to adverse environmental factors, and the timing of the stressful events, given that prenatal life, infancy, childhood, and adolescence are critical periods characterized by increased vulnerability to stressors.
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    Annual Review of Physiology 67 (2005), S. 285-308 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Tremendous progress has been made in elucidating numerous critical aspects of estrogen signaling. New tools and techniques have enabled detailed molecular analysis of components that direct estrogen responses. At the other end of the spectrum, generation of a multiplicity of transgenic animals has allowed analysis of the physiological roles of the estrogen-signaling components in biologically relevant models. Here, we review the ever-increasing body of knowledge in the field of estrogen biology, especially as applied to the female reproductive processes.
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    Annual Review of Physiology 67 (2005), S. 377-409 
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    Notes: In many species the pancreatic duct epithelium secretes HCO3 ions at a concentration of around 140 mM by a mechanism that is only partially understood. We know that HCO3 uptake at the basolateral membrane is achieved by Na+-HCO3 cotransport and also by a H+-ATPase and Na+/H+ exchanger operating together with carbonic anhydrase. At the apical membrane, the secretion of moderate concentrations of HCO3 can be explained by the parallel activity of a Cl/HCO3 exchanger and a Cl conductance, either the cystic fibrosis transmembrane conductance regulator (CFTR) or a Ca2+-activated Cl channel (CaCC). However, the sustained secretion of HCO3 into a HCO3 -rich luminal fluid cannot be explained by conventional Cl/HCO3 exchange. HCO3 efflux across the apical membrane is an electrogenic process that is facilitated by the depletion of intracellular Cl, but it remains to be seen whether it is mediated predominantly by CFTR or by an electrogenic SLC26 anion exchanger.
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    Annual Review of Physiology 67 (2005), S. 471-490 
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    Notes: The intestines play an important role in the absorption and secretion of nutrients. The colon is the final area for recapturing electrolytes and water prior to excretion, and in order to maintain this electrolyte homeostasis, a complex interaction between secretory and absorptive processes is necessary. Until recently it was thought that secretion and absorption were two distinct processes associated with either crypts or surface cells, respectively. Recently it was demonstrated that both the surface and crypt cells can perform secretory and absorptive functions and that, in fact, these functions can be going on simultaneously. This issue is important in the complexities associated with secretory diarrhea and also in attempting to develop treatment strategies for intestinal disorders. Here, we update the model of colonic secretion and absorption, discuss new issues of transporter activation, and identify some important new receptor pathways that are important modulators of the secretory and absorptive functions of the colon.
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    Annual Review of Physiology 67 (2005), S. 557-572 
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    Notes: Reabsorption of amino acids, similar to that of glucose, is a major task of the proximal kidney tubule. Various amino acids are actively transported across the luminal brush border membrane into proximal tubule epithelial cells, most of which by cotransport. An important player is the newly identified cotransporter (symporter) B0AT1 (SLC6A19), which imports a broad range of neutral amino acids together with Na+ across the luminal membrane and which is defective in Hartnup disorder. In contrast, cationic amino acids and cystine are taken up in exchange for recycled neutral amino acids by the heterodimeric cystinuria transporter. The basolateral release of some neutral amino acids into the extracellular space is mediated by unidirectional efflux transporters, analogous to GLUT2, that have not yet been definitively identified. Additionally, cationic amino acids and some other neutral amino acids leave the cell basolaterally via heterodimeric obligatory exchangers.
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    Annual Review of Physiology 67 (2005), S. 663-696 
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    Notes: Surfactant protein C (SP-C) is a hydrophobic 35-amino acid peptide that co-isolates with the phospholipid fraction of lung surfactant. SP-C represents a structurally and functionally challenging protein for the alveolar type 2 cell, which must synthesize, traffic, and process a 191Đ??197-amino acid precursor protein through the regulated secretory pathway. The current understanding of SP-C biosynthesis considers the SP-C proprotein (proSP-C) as a hybrid molecule that incorporates structural and functional features of both bitopic integral membrane proteins and more classically recognized luminal propeptide hormones, which are subject to post-translational processing and regulated exocytosis. Adding to the importance of a detailed understanding of SP-C biosynthesis has been the recent association of mutations in the proSP-C sequence with chronic interstitial pneumonias in children and adults. Many of these mutations involve either missense or deletion mutations located in a region of the proSP-C molecule that has structural homology to the BRI family of proteins linked to inherited degenerative dementias. This review examines the current state of SP-C biosynthesis with a focus on recent developments related to molecular and cellular mechanisms implicated in the emerging role of SP-C mutations in the pathophysiology of diffuse parenchymal lung disease.
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    Annual Review of Physiology 67 (2005), S. 595-621 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Exocytosis is fundamental in biology and requires an orchestra of proteins and other constituents to fuse a vesicle with the plasma membrane. Although the molecular fusion machinery appears to be well conserved in evolution, the process itself varies considerably with regard to the diversity of physico-chemical and structural factors that govern the delay between stimulus and fusion, the expansion of the fusion pore, the release of vesicle content, and, finally, its extracellular dispersion. Exocytosis of surfactant is unique in many of these aspects. This review deals with the secretory pathway of pulmonary surfactant from the type II cell to the air-liquid interface, with focus on the distinct mechanisms and regulation of lamellar body (LB) fusion and release. We also discuss the fate of secreted material until it is rearranged into units that finally function to reduce the surface tension in the lung.
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 67 (2005), S. 759-778 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Numerous Cl channels have been identified in the kidney using physiological approaches and thus are thought to be involved in a range of physiological processes, including vectorial transepithelial Cl transport, cell volume regulation, and vesicular acidification. In addition, expression of genes from several Cl channel gene families has also been observed. However, the molecular characteristics of a number of Cl channels within the kidney are still unknown, and the physiological roles of Cl channels identified by molecular means remain to be determined. A gene knockout approach using mice might shed further light on the characteristics of these various Cl channels. In addition, study of diseases involving Cl channels (channelopathies) might clarify the physiological role of specific Cl channels. To date, more is known about CLC Cl channels than any other Cl channels within the kidney. This review focuses on the physiological roles of CLC Cl channels within the kidney, particularly kidney-specific ClC-K Cl channels, as well as the recently identified maxi anion channel in macula densa, which is involved in tubulo-glomerular feedback.
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    Annual Review of Physiology 68 (2006), S. 431-459 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: The FXYD proteins are a family of seven homologous single transmembrane segment proteins (FXYD1Đ??7), expressed in a tissue-specific fashion. The FXYD proteins modulate the function of Na,K-ATPase, thus adapting kinetic properties of active Na+ and K+ transport to the specific needs of different cells. Six FXYD proteins ( 1Đ??5, 7 ) are known to interact with Na,K-ATPase and affect its kinetic properties in specific ways. Although effects of FXYD proteins on parameters such as K1/2Na+, K1/2K+, KmATP, and Vmax are modest, usually twofold, these effects may have important long-term consequences for homeostasis of cation balance. In this review we summarize basic features of FXYD proteins and present recent evidence for functional effects, structure-function relations and structural interactions with Na,K-ATPase. We then discuss possible physiological roles, based on in vitro observations and newly available knockout mice models. Finally, we also consider evidence that FXYD proteins affect functioning of other ion transport systems.
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    Annual Review of Physiology 68 (2006), S. 51-66 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Communication between endothelial cells and cardiomyocytes regulates not only early cardiac development but also adult cardiomyocyte function, including the contractile state. In the normal mammalian myocardium, each cardiomyocyte is surrounded by an intricate network of capillaries and is next to endothelial cells. Cardiomyocytes depend on endothelial cells not only for oxygenated blood supply but also for local protective signals that promote cardiomyocyte organization and survival. While endothelial cells direct cardiomyocytes, cardiomyocytes reciprocally secrete factors that impact endothelial cell function. Understanding how endothelial cells communicate with cardiomyocytes will be critical for cardiac regeneration, in which the ultimate goal is not simply to improve systolic function transiently but to establish new myocardium that is both structurally and functionally normal in the long term.
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    Annual Review of Physiology 67 (2005), S. 39-67 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Although well known as the location of the mechanism by which the cardiac sarcomere is activated by Ca2+ to generate force and shortening, the thin filament is now also recognized as a vital component determining the dynamics of contraction and relaxation. Molecular signaling in the thin filament involves steric, allosteric, and cooperative mechanisms that are modified by protein phosphorylation, sarcomere length and load, the chemical environment, and isoform composition. Approaches employing transgenesis and mutagenesis now permit investigation of these processes at the level of the systems biology of the heart. These studies reveal that the thin filaments are not merely slaves to the levels of Ca2+ determined by membrane channels, transporters and exchangers, but are actively involved in beat to beat control of cardiac function by neural and hormonal factors and by the Frank-Starling mechanism.
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    Annual Review of Physiology 67 (2005), S. 177-201 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Recent meta-analyses have shown that the effects of climate change are detectable and significant in their magnitude, but these studies have emphasized the utility of looking for large-scale patterns without necessarily understanding the mechanisms underlying these changes. Using a series of case studies, we explore the potential pitfalls when one fails to incorporate aspects of physiological performance when predicting the consequences of climate change on biotic communities. We argue that by considering the mechanistic details of physiological performance within the context of biophysical ecology (engineering methods of heat, mass and momentum exchange applied to biological systems), such approaches will be better poised to predict where and when the impacts of climate change will most likely occur.
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    Annual Review of Physiology 67 (2005), S. 491-514 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: 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.
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 67 (2005), S. 623-661 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Past studies have primarily focused on how altered lung vascular growth and development contribute to pulmonary hypertension. Recently, basic studies of vascular growth have led to novel insights into mechanisms underlying development of the normal pulmonary circulation and the essential relationship of vascular growth to lung alveolar development. These observations have led to new concepts underlying the pathobiology of developmental lung disease, especially the inhibition of lung growth that characterizes bronchopulmonary dysplasia (BPD). We speculate that understanding basic mechanisms that regulate and determine vascular growth will lead to new clinical strategies to improve the long-term outcome of premature babies with BPD.
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    Annual Review of Physiology 67 (2005), S. 719-758 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Calcium-activated chloride channels (CaCCs) play important roles in cellular physiology, including epithelial secretion of electrolytes and water, sensory transduction, regulation of neuronal and cardiac excitability, and regulation of vascular tone. This review discusses the physiological roles of these channels, their mechanisms of regulation and activation, and the mechanisms of anion selectivity and conduction. Despite the fact that CaCCs are so broadly expressed in cells and play such important functions, understanding these channels has been limited by the absence of specific blockers and the fact that the molecular identities of CaCCs remains in question. Recent status of the pharmacology and molecular identification of CaCCs is evaluated.
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    Annual Review of Physiology 67 (2005), S. 701-718 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: The assembly of the cystic fibrosis transmembrane regulator (CFTR) chloride channel is of interest from the broad perspective of understanding how ion channels and ABC transporters are formed as well as dealing with the mis-assembly of CFTR in cystic fibrosis. CFTR is functionally distinct from other ABC transporters because it permits bidirectional permeation of anions rather than vectorial transport of solutes. This adaptation of the ABC transporter structure can be rationalized by considering CFTR as a hydrolyzable-ligand-gated channel with cytoplasmic ATP as ligand. Channel gating is initiated by ligand binding when the protein is also phosphorylated by protein kinase A and made reversible by ligand hydrolysis. The two nucleotide-binding sites play different roles in channel activation. CFTR self-associates, possibly as a function of its activation, but most evidence, including the low-resolution three-dimensional structure, indicates that the channel is monomeric. Domain assembly and interaction within the monomer is critical in maturation, stability, and function of the protein. Disease-associated mutations, including the most common, ??F508, interfere with domain folding and association, which occur both co- and post-translationally. Intermolecular interactions of mature CFTR have been detected primarily with the N- and C-terminal tails, and these interactions have some impact not only on channel function but also on localization and processing within the cell. The biosynthetic processing of the nascent polypeptide leading to channel assembly involves transient interactions with numerous chaperones and enzymes on both sides of the endoplasmic reticulum membrane.
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    Annual Review of Physiology 67 (2005), S. 809-839 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: The CLC family comprises a group of integral membrane proteins whose major action is to translocate chloride (Cl) ions across the cell membranes. Recently, the structures of CLC orthologues from two bacterial species, Salmonella typhimurium and Escherichia coli, were solved, providing the first framework for understanding the operating mechanisms of these molecules. However, most of the previous mechanistic understanding of CLC channels came from electrophysiological studies of a branch of the channel family, the muscle-type CLC channels in vertebrate species. These vertebrate CLC channels were predicted to contain two identical but independent pores, and this hypothesis was confirmed by the solved bacterial CLC structures. The opening and closing of the vertebrate CLC channels are also known to couple to the permeant ions via their binding sites in the ion-permeation pathway. The bacterial CLC structures can probably serve as a structural model to explain the gating-permeation coupling mechanism. However, the CLC-ec1 protein in E. coli was most recently shown to be a Cl-H+ antiporter, but not an ion channel. The molecular basis to explain the difference between vertebrate and bacterial CLCs, especially the distinction between an ion channel and a transporter, remains a challenge in the structure/function studies for the CLC family.
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    Annual Review of Physiology 68 (2006), S. 685-717 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Ion channels are pore-forming transmembrane proteins that allow ions to permeate biological membranes. Pore structure plays a crucial role in determining the ion permeation and selectivity properties of particular channels. In the past few decades, efforts have been undertaken to identify key elements of the pore regions of different classes of ion channels. In this review, we summarize current knowledge about permeation and selectivity of channel proteins from the transient receptor potential (TRP) superfamily. Whereas all TRP channels are permeable for cations, only two TRP channels are impermeable for Ca2+ (TRPM4, TRPM5), and two others are highly Ca2+ permeable (TRPV5, TRPV6). Despite the great advances in the TRP channel field during the past decade, only a limited number of reports have dealt with functional characterization of pore properties, biophysical aspects of cation permeation, or description of pore structures of TRP channels. This review gives an overview of available experimental and theoretical data and discusses the functional impact of pore-structure modifications on TRP channel properties.
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