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  • Life and Medical Sciences  (779)
  • 1995-1999  (779)
  • 1965-1969
  • 1997  (779)
  • 1
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    BioEssays 19 (1997), S. 75-84 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Fluorescent in situ hybridization technology is one of the most exciting and versatile research tools to be developed in recent years. It has enabled research to progress at a phenomenal rate in diverse areas of basic research as well as in clinical medicine. Fluorescent in situ hybridization has applications in physical mapping, the study of nuclear architecture and chromatin packaging, and the investigation of fundamental principles of biology such as DNA replication, RNA processing, gene amplification, gene integration and chromatin elimination. This review highlights some of these areas and provides source material for the reader who seeks more information on a specific field.
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  • 2
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
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  • 3
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    New York, NY : Wiley-Blackwell
    BioEssays 19 (1997), S. 91-92 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
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  • 4
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    New York, NY : Wiley-Blackwell
    BioEssays 19 (1997), S. 127-135 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Evidence from Drosophila and also vertebrates predicts that two different sets of instructions may determine the development of the rostral and caudal parts of the body. This implies different cellular and inductive processes during gastrulation, whose genetic requirements remain to be understood. To date, four genes encoding transcription factors expressed in the presumptive vertebrate head during gastrulation have been studied at the functional level: Lim-1, Otx-2, HNF-3β and goosecoid. We discuss here the potential functions of these genes in the formation of rostral head as compared to posterior head and trunk, and in the light of recent fate map and expression analyses in mouse, chick, Xenopus and zebrafish. These data indicate that Lim-1, Otx-2 and HNF-3β may be involved in the same genetic pathway controlling the formation of the prechordal mesendoderm, which is subsequently required for rostral head development. goosecoid may act in a parallel pathway, possibly in conjunction with other, yet unidentified, factors.
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  • 5
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    New York, NY : Wiley-Blackwell
    BioEssays 19 (1997), S. 147-152 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: From stem cells to oocyte, Drosophila germ cells undergo a short, defined lineage. Molecular genetic analyses of a collection of female sterile mutations have indicated that a germ cell-specific organelle called the fusome has a central role at several steps in this lineage. The fusome grows from a prominent spherical organelle to an elongated and branched structure that connects all mitotic sisters in a germ cell syncytium. The organelle is assembled from proteins normally found in the membrane skeleton and, additionally, contains an extensive membranous reticulum, the probable product of differentiation-dependent vesicle trafficking. This review briefly summarizes a current view of the processes that drive germ cell differentiation, particularly the various roles that the fusome might play in regulating the developmental events. Future efforts will consider to what extent an organelle assembly-dependent model for differentiation is heuristic and whether the Drosophila fusome represents a homolog of a similar organelle in vertebrate lymphocytes.
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  • 6
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    New York, NY : Wiley-Blackwell
    BioEssays 19 (1997), S. 153-160 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The glucocorticoid receptor belongs to an important class of transcription factors that alter the expression of target genes in response to a specific hormone signal. The glucocorticoid receptor can function at least at three levels: (1) recruitment of the general transcription machinery; (2) modulation of transcription factor action, independent of DNA binding, through direct protein-protein interactions; and (3) modulation of chromatin structure to allow the assembly of other gene regulatory proteins and/or the general transcription machinery on the DNA. This review will focus on the multifaceted nature of protein-protein interactions involving the glucocorticoid receptor and basal transcription factors, coactivators and other transcription factors, occurring at these different levels of regulation.
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  • 7
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    New York, NY : Wiley-Blackwell
    BioEssays 19 (1997), S. 161-166 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Over recent years, evidence has been accumulating in favour of the free radical theory of aging, first proposed by Harman. Despite this, an understanding of the mechanism by which cells might succumb to the effects of free radicals has proved elusive. This paper proposes such a mechanism, based on a previously unexplored hypothesis for the proliferation of mutant mitochondrial DNA: that mitochondria with reduced respiratory function, due to a mutation or deletion affecting the respiratory chain, suffer less frequent lysosomal degradation, because they inflict free radical damage more slowly on their own membranes. Once such a mutation occurs in a mitochondrion of a non-dividing cell, therefore, mitochondria carrying it will rapidly populate that cell, thereby destroying the cell's respiratory capability. The accumulation of cells that have undergone this transition results in aging at the organismal level. The consistency of the hypothesis with known facts is discussed, and technically feasible tests are suggested, of both the proposed mechanism and its overall contribution to mammalian aging.
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  • 8
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    New York, NY : Wiley-Blackwell
    BioEssays 19 (1997), S. 225-231 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: To understand how morphological characters change during evolution, we need insight into the evolution of developmental processes. Comparative developmental approaches that make use of our fundamental understanding of development in certain model organisms have been initiated for different animal systems and flowering plants. Nematodes provide a useful experimental system with which to investigate the genetic and molecular alterations underlying evolutionary changes of cell fate specification in development, by comparing different species to the genetic model system Caenorhabditis elegans. In this review, I will first discuss the different types of evolutionary alterations seen at the cellular level by focusing mainly on the analysis of vulva development in different species. The observed alterations involve changes in cell lineage, cell migration and cell death, as well as induction and cell competence. I then describe a genetic approach in the nematode Pristionchus pacificus that might identify those genetic and molecular processes that cause evolutionary changes of cell fate specification.
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  • 9
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    New York, NY : Wiley-Blackwell
    BioEssays 19 (1997), S. 233-240 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Unlike the most well-characterized prokaryotic polymerase, E. Coli DNA pol I, none of the eukaryotic polymerases have their own 5′ to 3′ exonuclease domain for nick translation and Okazaki fragment processing. In eukaryotes, FEN-1 is an endo-and exonuclease that carries out this function independently of the polymerase molecules. Only seven nucleases have been cloned from multicellular eukaryotic cells. Among these, FEN-1 is intriguing because it has complex structural preferences; specifically, it cleaves at branched DNA structures. The cloning of FEN-1 permitted establishment of the first eukaryotic nuclease family, predicting that S. cerevisiae RAD2 (S. pombe Rad13) and its mammalian homolog, XPG, would have similar structural specficity. The FEN-1 nuclease family includes several similar enzymes encoded by bacteriophages. The crystal structures of two enzymes in the FEN-1 nuclease family have been solved and they provide a structural basis for the interesting steric requirements of FEN-1 substrates. Because of their unique structural specificities, FEN-1 and its family members have important roles in DNA replication, repair and, potentially, recombination. Recently, FEN-1 was found to specifically associate with PCNA, explaining some aspects of FEN-1 function during DNA replication and potentially in DNA repair.
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  • 10
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    New York, NY : Wiley-Blackwell
    BioEssays 19 (1997), S. 249-255 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Knockout experiments in Tetrahymena show that linker histone H1 is not essential for nuclear assembly or cell viability. These results, together with a series of biochemical and cell biological observations, challenge the existing paradigm that requires linker histones to be a key organizing component of higher-order chromatin structure. The H1 Knockouts also reveal a much more subtle role for H1. Instead of acting as a general transcriptional repressor, H1 is found to regulate a limited number of specific genes. Surprisingly, H1 can both activate and repress transcription. We discuss how this architectural protein might accomplish this important regulatory role.
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  • 11
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    BioEssays 19 (1997), S. 241-247 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Mammalian sperm undergo discharge of a single, anterior secretory granule following their attachment to the zona pellucida surrounding the oocyte. This secretory discharge is known for historical reasons as the acrosome reaction. It fulfils a number of purposes and without it, sperm are unable to penetrate the zona pellucida and fuse with the oocyte. In this review, we focus on the role of the acrosome reaction in the development of fusion competence in sperm. Any naturally occurring membrane fusion has two major sequential steps: a docking or adhesion step, in which two membranes adhere, and a fusion step, in which their lipid bilayers are destabilized and merged and a cellular compartment is either created or destroyed. Recent evidence suggests that there is an important role for oocyte integrins and sperm-bound disintegrins in mammalian sperm/oocyte adhesion and fusion. The fusion mechanism employed by sperm remains poorly understood, however, and circumstantial evidence suggests it is more complex than the interaction between a single protein species and its target. Sperm/oocyte fusion is probably the most accessible eukaryotic model for intercellular fusion currently available, partly because it is temporally separated from gene expression. Elucidation of the mechanism of sperm/oocyte fusion may throw light on the mechanism of other intercellular fusions such as myoblast fusion, and the evolutionary relationship of intercellular membrane fusion to intracellular membrane fusion.
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  • 12
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    BioEssays 19 (1997), S. 257-262 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The phenomenon of ‘canalization’ - the genetic capacity to buffer developmental pathways against mutational or environmental perturbations - was first characterized in the late 1930s and early 1940s. Despite enormous subsequent progress in understanding the nature of the genetic material and the molecular basis of gene expression, there have been few attempts to interpret the classical work on canalization in molecular genetic terms. Some recent findings, however, bear on one form of canalization, ‘genetic canalization’, the stabilization of development against mutational effects. These data indicate that co-expressed paralogous genes can function as mutual ‘back-up’ elements in developmental processes. Paralogues, however, are far from the only basis of canalization: other genetic sources can be readily envisaged and some of these are described here. The evolutionary questions about genetic canalization and the mechanistic questions about developmental instability that still need to be addressed are also briefly discussed.
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  • 13
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    BioEssays 19 (1997), S. 263-266 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: This is the second of two ‘Roots’ articles from Dr Ernst Mayr; the first appeared in the February issue. The article that follows is Dr Mayr's address on the 50th anniversary of the founding of the Society for the Study of Evolution, St Louis, USA, June 19, 1996.
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  • 14
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    New York, NY : Wiley-Blackwell
    BioEssays 19 (1997) 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
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  • 15
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    BioEssays 19 (1997), S. 347-352 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: There is growing evidence that mutations can arise in non-dividing cells (both bacterial and mammalian) in the absence of chromosomal replication. The processes that are involved are still largely unknown but may include two separate mechanisms. In the first, DNA lesions resulting from the action of endogenous mutagens may give rise to RNA transcripts with miscoded bases. If these confer the ability to initiate DNA replication, the DNA lesions may have an opportunity to miscode during replication and thus could give rise to apparently ‘adaptive’ mutations. A second mechanism is suggested by recent work in starved bacteria, showing that there is much more turnover of chromosomal DNA than has been previously thought. This could permit polymerase errors to lead to mutations in non-dividing cells. Such cryptic DNA synthesis, which may essentially replace existing DNA rather than duplicating it, could, in principle, act as an additional source of variability on which selection may act, initially in the absence of cell division. In mammals such processes would undoubtedly have implications for germ cell mutagenesis and carcinogenesis.
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    New York, NY : Wiley-Blackwell
    BioEssays 19 (1997) 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
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  • 17
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    BioEssays 19 (1997), S. 445-445 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
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    Topics: Biology , Medicine
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  • 18
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    BioEssays 19 (1997), S. 447-450 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The viral and cellular forms of the Src protein tyrosine kinases take a prototypic role in oncology and signal transduction research, by virtue of being holders of an impressive number of ‘firsts’. Our understanding of the biochemistry and physiology of Src has therefore always been used as a reference for our general advancement in the field of protein phosphorylation and growth control. The recent solution of the crystal structure of two members of the Src family(1,2) represents a milestone in these disciplines and, as usual, provides a general lookout post for developments to come.
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  • 19
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    BioEssays 19 (1997), S. 451-454 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Microtubules are organized into diverse cellular structures in multicellular organisms. How is such diversity generated? Although highly conserved overall, variable regions within α- and β-tubulins show divergence from other α- and β-tubulins in the same species, but show conservation among different species. Such conservation raises the question of whether diversity in tubulin structure mediates diversity in microtubule organization. Recent studies probing the function of β-tubulin isotypes in axonemes of insects(1) suggest that tubulin structure, through interactions with extrinsic proteins, can direct the architecture and supramolecular organization of microtubules.
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    BioEssays 19 (1997), S. 455-458 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Clp ATPase chaperone proteins are found in procaryotes and eucaryotes. Recently, ClpC of Bacillus subtilis was found to be part of a regulatory switch(1). ClpC, in combination with the MecA and ComS proteins, regulates the activity of a transcription factor, ComK, which is necessary for the development of genetic competence (the ability to bind and take up exogenous DNA). The complex of ClpC:MecA:ComK renders ComK inactive. Interaction between ComS and the ternary complex releases active ComK. This regulatory switch controls ComK activity in response to cell density signals that affect production of ComS. Regulated interaction between Clp ATPases and target proteins might prove to be widespread.
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    BioEssays 19 (1997), S. 459-468 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Every cartilage and bone in the vertebrate skeleton has a precise shape and position. The head skeleton develops in the embryo from the neural crest, which emigrates from the neural ectoderm and forms the skull and pharyngeal arches. Recent genetic data from mice and zebrafish suggest that cells in the pharyngeal segments are specified by positional information in at least two dimensions, Hox genes along the anterior-posterior axis and other homeobox genes along the dorsal-ventral axis within a segment. Many zebrafish and human mutant phenotypes indicate that additional genes are required for the development of groups of adjacent pharyngeal arches and for patterning along the mediolateral axis of the skull. The complementary genetic approaches in humans, mice and fish reveal networks of genes that specify the complex morphology of the head skeleton along a relatively simple set of coordinates.
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  • 22
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    BioEssays 19 (1997), S. 571-579 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The biochemical mechanism by which the phytochrome family of plant sensory photoreceptors transmit perceived informational light signals downstream to transduction pathway components is undetermined. The recent sequencing of the entire genome of the cyanobacterium Synechocystis, however, has revealed a protein that has an NH2-terminal domain with striking sequence similarity to the photosensory NH2-terminal domain of the phytochromes, and a COOH-terminal domain strongly related to the transmitter histidine kinase module of bacterial two-component sensors. The Synechocystis protein is capable of autocatalytic chromophore ligation and exhibits photoreversible light-absorption changes analogous to the phytochromes, indicating its capacity to function as an informational photoreceptor. Together with earlier observations that the COOH-terminal domains of the plant phytochromes also have sequence similarity to the histidine kinases, these data suggest that the cyanobacteria utilize photoregulated histidine kinases as a sensory system and that the plant phytochromes may be evolutionary descendants of these photoreceptors.
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    BioEssays 19 (1997), S. 581-591 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Transforming growth factor-β (TGF-β) and its related proteins regulate broad aspects of body development, including cell proliferation, differentiation, apoptosis and gene expression, in various organisms. Deregulated TGF-β function has been causally implicated in the generation of human fibrotic disorders and in tumor progression. Nevertheless, the molecular mechanisms of TGF-β action remained essentially unknown until recently. Here, we discuss recent progress in our understanding of the mechanism of TGF-β signal transduction with respect to the regulation of gene expression, the control of cell phenotype and the potential usage TGF-β for the treatment of human diseases.
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    BioEssays 19 (1997), S. 607-613 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: SCL (TAL1/TCL5) is a member of the helix-loop-helix family of transcription factors. Originally identified because of its involvement in a tumour-specific chromosomal translocation, overexpression of the SCL gene is the most common molecular abnormality found in human T cell leukaemia. Transgenic models have now formally demonstrated that overexpression of SCL within the T cell lineage is capable of causing malignant transformation. Gene targeting experiments have revealed that the SCL gene is crucial for the development of primitive haematopoiesis in the mouse and is also required for the generation of all adult haematopoietic lineages. Biochemical studies have indicated some of the proteins which interact with SCL and this has refined the hypotheses concerning the mechanisms by which SCL plays a role in leukaemogenesis and haematopoietic development.
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    BioEssays 19 (1997), S. 743-743 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
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    BioEssays 19 (1997), S. 744-744 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
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    BioEssays 19 (1997) 
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    BioEssays 19 (1997), S. 745-746 
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    BioEssays 19 (1997), S. 751-753 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Mitochondria are essential subcellular organelles containing an extranuclear genome (mtDNA). Mutations in mtDNA have recently been identified as causing a variety of human hereditary diseases. In most of these cases, the tissues of the affected individual contain a mixture of mutant and normal mtDNA, with this ratio determining the severity of symptoms. Stochastic factors alone have generally been believed to determine this ratio. Jenuth et al.(1), however, examining mice that contain a mixture of mtDNA types, show evidence of strong selective forces at work in favoring one mtDNA variant over another in some tissues.
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    BioEssays 19 (1997), S. 747-750 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Although the precise function of utrophin at the postsynaptic membrane of the neuromuscular junction still remains unclear, despite recent genetic ‘knockout’ experiments(1,2), a separate study in a transgenic mouse model system for Duchenne muscular dystrophy (DMD) has nonetheless shown that overexpression of utrophin into extrasynaptic regions of muscle fibers can functionally compensate for the lack of dystrophin and alleviate the muscle pathology(3). In this context, the next step is to identify the mechanisms presiding over expression of utrophin at the neuromuscular synapse in attempts to induce its expression throughout DMD muscle fibers. In fact, additional studies have shown that an important DNA element contained with the utrophin promoter may confer synapse-specific expression to the utrophin gene(4,5). Identification of the events culminating in the transaction of the utrophin gene within synaptic myonuclei should provide important cues for the development of an effective therapeutic strategy for DMD.
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    BioEssays 19 (1997), S. 755-765 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Pax genes are a family of development control genes that encode nuclear transcription factors. They are characterized by the presence of the paired domain, a conserved amino acid motif with DNA-binding activity. Originally, paired-box-containing genes were detected in Drosophila malenogaster, where they exert multiple functions during embryogenesis. In vertebrates, Pax genes are also involved in embryogenesis. Mutations in four out of nine characterized Pax genes have been associated with either congenital human diseases such as Waardenburg syndrome (PAX3), Aniridia (PAX6), Peter's anomaly (PAX6), renal coloboma syndrome (PAX2), Small eye (Pax6), (Pax21Neu), which all show defects in development. Recently, analysis of spontaneous and transgenic mouse mutants has revealed that vertebrate Pax genes are key regulators during organogenesis of kidney, eye, ear, nose, limb muscles, vertebral column and brain. Like their Drosophila counterparts, vertebrate Pax genes are involved in pattern formation during embryogenesis, possibly by determiing the time and place of organ initiation of morphogenesis. For most tissues, however, the nature of the primary development action of Pax transcription factors remains to be elucidated. One predominant theme is signal transduction during tissue interactions, which may lead to a position-specific regulation of cell proliferation.
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    BioEssays 19 (1997), S. 767-775 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Nerve processes elongate, branch and form synaptic contacts in a highly regulated and specific manner. Long-distance axon elongation is restricted to the main phase of axon formation during development, but can be reinduced upon lesions in the adult (regeneration). It correlates with the expression of defined genes, including proteins involved in signalling (e.g. src, NCAM, integrins), transcription factors (e.g. c-jun) and structural proteins (e.g. actin and tubulin isoforms). Activation of an axon elongation program may require bcl-2. The formation and growth of local branches (sprouting) is controlled by mechanisms in the target region. In addition, the expression of growth-associated proteins such as GAP-43 and CAP-23 in neurons lowers the threshold for nerve sprouting and potentiates its vigour. Recent studies suggest that nerve sprouting and long-distance elongation depend on the expression of different intrinsic components in neurons. One implication of these findings is that the differential expression of genes facilitating local branching may affect structural plasticity in the intact adult nervous system.
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  • 33
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    BioEssays 19 (1997), S. 777-786 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Adaptive immunity is unique to the vertebrates, and the molecules involved (including immunoglobulins, T cell receptors and the major histocompatibility complex molecules) seem to have diversified very rapidly early in vertebrate history. Reconstruction of gene phylogenies has yielded insights into the evolutionary origin of a number of molecular systems, including the complement system and the major histocompatibility complex (MHC). These analyses have indicated that the C5 component of complement arose by gene duplication prior to the divergence of C3 and C4, which suggests that the alternative complement pathway was the first to evolve. In the case of the MHC, phylogenetic analysis supports the hypothesis that MHC class II molecules evolved before class I molecules. The fact that the MHC-linked proteasome components that specifically produce peptides for presentation by class I MHC appear to have originated before the separation of jawed and jawless vertebrates suggests that the MHC itself may have been present at this time. Immmune system gene families have evolved by gene duplication, interlocus recombination and (in some cases) positive Darwinian selection favoring diversity at the amino acid level.
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    BioEssays 19 (1997) 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
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    BioEssays 19 (1997), S. 1043-1044 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
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    BioEssays 19 (1997), S. 1099-1108 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: This article outlines the rationale for a molecular genetic study of social behavior, and explains why social insects are good models. Summaries of research on brain and behavior in two species, honey bees and fire ants, are presented to illustrate the richness of the behavioral phenomena that can be addressed with social insects and to show how they are beginning to be used to study genes that influence social behavior. We conclude by considering the problems and potential of this emerging field.
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  • 37
    ISSN: 0197-8462
    Keywords: cell cycle ; electromagnetic field ; nonthermal effects ; yeast ; extremely high frequency ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Exponentially growing cells of the yeast Saccharomyces cerevisiae were exposed to electromagnetic fields in the frequency range from 41.682 GHz to 41.710 GHz in 2 MHz increments at low power densities (0.5 μW/cm2 and 50 μW/cm2) to observe possible nonthermal effects on the division of this microorganism. The electronic setup was carefully designed and tested to allow precise determination and stability of the electromagnetic field parameters as well as to minimize possible effects of external sources. Two identical test chambers were constructed in one exposure system to perform concurrent control and test experiments at every frequency step under well-controlled exposure conditions. Division of cells was assessed via time-lapse photography. Control experiments showed that the cells were dividing at submaximal rates, ensuring the possibility of observing either an increase or a decrease of the division rate. The data from several independent series of exposure experiments and from control experiments show no consistently significant differences between exposed and unexposed cells. This is in contrast to previous studies claiming nonthermal effects of electromagnetic fields in this frequency range on the division of S. cerevisiae cells. Possible reasons for this difference are discussed. Bioelectromagnetics 18:142-155, 1997. © 1997 Wiley-Liss, Inc.
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    Bioelectromagnetics 18 (1997), S. 25-27 
    ISSN: 0197-8462
    Keywords: magnetic field ; ion motion ; resonance properties ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: To analyze the mechanisms of action of weak electric and magnetic fields on ion motion in solution, a new approach is outlined allowing for collective interactions of large ionic ensembles with the external field. Bioelectromagnetics 18:25-27, 1997. © 1997 Wiley-Liss, Inc.
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    Bioelectromagnetics 18 (1997), S. 28-35 
    ISSN: 0197-8462
    Keywords: extremely low frequency ; case-control study ; neurodegenerative disease ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: In an hypothesis-generating case-control study of amyotrophic lateral sclerosis, lifetime occupational histories were obtained. The patients (n = 28) were clinic based. The occupational exposure of interest in this report is electromagnetic fields (EMFs). This is the first and so far the only exposure analyzed in this study. Occupational exposure up to 2 years prior to estimated disease symptom onset was used for construction of exposure indices for cases. Controls (n = 32) were blood and nonblood relatives of cases. Occupational exposure for controls was through the same age as exposure for the corresponding cases. Twenty (71%) cases and 28 (88%) controls had at least 20 years of work experience covering the exposure period. The occupational history and task data were used to classify blindly each occupation for each subject as having high, medium/high, medium, medium/low, or low EMF exposure, based primarily on data from an earlier and unrelated study designed to obtain occupational EMF exposure information on workers in “electrical” and “nonelectrical” jobs. By using the length of time each subject spent in each occupation through the exposure period, two indices of exposure were constructed: total occupational exposure (E1) and average occupational exposure (E2). For cases and controls with at least 20 years of work experience, the odds ratio (OR) for exposure at the 75th percentile of the E1 case exposure data relative to minimum exposure was 7.5 (P 〈 0.02; 95% Cl, 1.4-38.1) and the corresponding OR for E2 was 5.5 (P 〈 0.02; 95% CI, 1.3-22.5). For all cases and controls, the ORs were 2.5 (P 〈 0.1; 95% CI, 0.9-8.1) for E1 and 2.3 (P = 0.12; 95% CI, 0.8-6.6) for E2. This study should be considered an hypothesis-generating study. Larger studies, using incident cases and improved exposure assessment, should be undertaken. Bioelectromagnetics 18:28-35, 1997. © 1997 Wiley-Liss, Inc.
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    Bioelectromagnetics 18 (1997), S. 193-202 
    ISSN: 0197-8462
    Keywords: electromagnetic fields ; mechanical strain ; adaptation ; bone cells ; Wolff's law ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: The natural remodeling and adaptation of skeletal tissues in response to mechanical loading is a classic example of physical regulation in biology. It is largely because it involves forces that do not seem to fit into the familiar schemes of biochemical controls that bone adaptation mechanisms have intrigued us for at least a century. The effect of electromagnetic fields on organisms is another example of this, and the two have become linked in an attempt to explain bone remodeling (“Yasuda's hypothesis”). This paper re-examines the roles of endogenous and exogenous electromagnetic fields in the response of bone to mechanical forces. A series of experiments is reviewed in which mechanical and electrical stimuli were applied to implants in the medullary canal of rabbit long bones. The results suggest that endogenously generated electrical currents are not required to initiate mechanically stimulated bone formation, but that direct mechanical effects on bone cells is the more likely scenario. Based on this and other evidence from the literature, it is suggested that when exogenous electromagnetic stimuli are applied, bone cells respond by modulating the activity of more primary activators such as hormones, growth factors, cytokines, and mechanical forces. Bioelectromagnetics 18:193-202, 1997. © 1997 Wiley-Liss, Inc.
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  • 41
    ISSN: 0197-8462
    Keywords: electromagnetic fields ; gene expression ; transcription factors ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Rat PC12 pheochromocytoma cells have been treated with nerve growth factor and then exposed to athermal levels of a packet-modulated radiofrequency field at 836.55 MHz. This signal was produced by a prototype time-domain multiple-access (TDMA) transmitter that conforms to the North American digital cellular telephone standard. Three slot average power densities were used: 0.09, 0.9, and 9 mW/cm2. Exposures were for 20, 40, and 60 min and included an intermittent exposure regimen (20 min on/20 min off), resulting in total incubation times of 20, 60, and 100 min, respectively. Concurrent controls were sham exposed. After extracting total cellular RNA, Northern blot analysis was used to assess the expression of the immediate early genes, c-fos and c-jun, in all cell populations. No change in c-fos transcript levels were detected after 20 min exposure at each field intensity (20 min was the only time period at which c-fos message could be detected consistently). Transcript levels for c-jun were altered only after 20 min exposure to 9 mW/cm2 (average 38% decrease). Bioelectromagnetics 18:223-229, 1997. © 1997 Wiley-Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.
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  • 42
    ISSN: 0197-8462
    Keywords: biological effects of ELF magnetic fields ; attenuation of opioid analgaesia ; light-dependent magnetic field effects ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Exposure to extremely low frequency (ELF) magnetic fields has been shown to attenuate endogenous opioid peptide mediated antinociception or “analgaesia” in the terrestrial pulmonate snail, Cepaea nemoralis. Here we examine the roles of light in determining this effect and address the mechanisms associated with mediating the effects of the ELF magnetic fields in both the presence and absence of light. Specifically, we consider whether the magnetic field effects involve an indirect induced electric current mechanism or a direct effect such as a parametric resonance mechanism (PRM). We exposed snails in both the presence and absence of light at three different frequencies (30, 60, and 120 Hz) with static field values (BDC) and ELF magnetic field amplitude (peak) and direction (BAC) set according to the predictions of the PRM for Ca2+. Analgaesia was induced in snails by injecting them with an enkephalinase inhibitor, which augments endogenous opioid (enkephalin) activity. We found that the magnetic field exposure reduced this opioid-induced analgaesia significantly more if the exposure occurred in the presence rather than the absence of light. However, the percentage reduction in analgaesia in both the presence and absence of light was not dependent on the ELF frequency. This finding suggests that in both the presence and the absence of light the effect of the ELF magnetic field was mediated by a direct magnetic field detection mechanism such as the PRM rather than an induced current mechanism. Bioelectromagnetics 18:284-291, 1997. © 1997 Wiley-Liss, Inc.
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    Bioelectromagnetics 18 (1997), S. 293-298 
    ISSN: 0197-8462
    Keywords: MW radiation ; computerized time-averaging ; brain hemispheric asymmetry ; EEG ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Averaged electroencephalogram (EEG) frequency spectra were studied in eight unanesthetized and unmyorelaxed adult male rats with chronically implanted carbon electrodes in symmetrical somesthetic areas when a weak (0.1-0.2 mW/cm) microwave (MW, 945 MHz) field, amplitude-modulated at extremely low frequency (ELF) (4 Hz), was applied. Intermittent (1 min “On,” 1 min “Off”) field exposure (10-min duration) was used. Hemispheric asymmetry in frequency spectra (averaged data for 10 or 1 min) of an ongoing EEG was characterized by a power decrease in the 1.5-3 Hz range on the left hemisphere and by a power decrease in the 10-14 and 20-30 Hz ranges on the right hemisphere. No differences between control and exposure experiments were shown under these routines of data averaging. Significant elevations of EEG asymmetry in 10-14 Hz range were observed during the first 20 s after four from five onsets of the MW field, when averaged spectra were obtained for every 10 s. Under neither control nor pre- and postexposure conditions was this effect observed. These results are discussed with respect to interaction of MW fields with the EEG generators. Bioelectromagnetics 18:293-298, 1997. © 1997 Wiley-Liss, Inc.
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    Bioelectromagnetics 18 (1997), S. 299-306 
    ISSN: 0197-8462
    Keywords: ELF magnetic field exposure systems ; feedback control ; disturbance rejection ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Extremely low-frequency (ELF) magnetic field exposure systems are usually subject to field disturbances induced by external sources. Here, a method for designing a feedback control system for cancelling the effect of external ELF magnetic field disturbances on the magnetic field over the exposure area is presented. This method was used in the design of a feedback-controlled exposure system for an inverted microscope stage. The effectiveness of the proposed feedback control system for disturbance rejection was verified experimentally and by means of computer simulation. Bioelectromagnetics 18:299-306, 1997. © 1997 Wiley-Liss, Inc.
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    Bioelectromagnetics 18 (1997), S. 341-348 
    ISSN: 0197-8462
    Keywords: wound potential gradient ; ELF field ; zeta potential ; in situ electrophoresis ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: When a number of experimental studies in bioelectromagnetics were reviewed, those in which weak, exogenous extremely low frequency (ELF) fields were applied in fixed juxtaposition to their target tissues, were found to initiate mitogenesis or mitogenesis-related signals more successfully than when the target tissue moved freely during the irradiation. It is suggested that ELF fields in fixed juxtaposition to their target tissue and implanted foreign bodies or endogenous tissues with a significant zeta potential, mimic bioelectric fields generated at wounds. When the potential is high enough, they assist healing by moving cells into the wound and stimulating quiescent cells at the wound margin to cycle. Electrophoresis may help the initial migration of cells into the wound to form a clot, and migration of fibroblasts and epithelial cells from the wound margin. When exposed for a long time in a fixed juxtaposition to a potential gradient too weak to show in situ microelectrophoresis along the cell membrane surface, surface particles may coalesce to form microclusters, where like-charged surface particles are in close proximity, and growth factor receptor oligomerization and other cycle-initiating reactions are facilitated. Bioelectromagnetics 18:341-348, 1997. © 1997 Wiley-Liss, Inc.
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    Bioelectromagnetics 18 (1997), S. 244-249 
    ISSN: 0197-8462
    Keywords: extremely-low-frequency magnetic fields ; free-radical mechanism ; ion-oscillator models ; ion-resonance models ; magnetotransduction ; AC/DC combinations ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: An experimental test constraining the intrinsic time scale of a primary physical mechanism that detects extremely-low-frequency (ELF) magnetic fields in biological systems is proposed. The suggested test postulates that a transductive mechanism operating on time scales much shorter than the period of an applied magnetic field cannot obtain any information about the exposure conditions other than the absolute magnitude of the field. By generating field exposures that differ in their vector properties but are equivalent in their time-varying absolute amplitude, it is possible to differentiate between two broad classes of mechanisms: 1) those with intrinsic time scales comparable with or longer than those of the external influence, and 2) those that are much faster than the period of the applied field. The hypothesis assumes an experimental model proven to respond to magnetic fields and sensitive to a change of about a factor of two in one of the field parameters (AC, DC amplitude or frequency). The case of general linearly polarized fields is discussed, and an analytical solution for the case of perpendicular AC/DC fields is given. Bioelectromagnetics 18:244-249, 1997 © 1997 Wiley-Liss, Inc.
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    Bioelectromagnetics 18 (1997), S. 478-490 
    ISSN: 0197-8462
    Keywords: organ dosimetry ; low-frequency magnetic induction ; numerical modelling ; FDTD calculations ; impedance method ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: The effects of human body model resolution on computed electric fields induced by 60 Hz uniform magnetic fields are investigated. A recently-developed scalar potential finite difference code for low-frequency electromagnetic computations is used to model induction in two anatomically realistic human body models. The first model consists of 204 290 cubic voxels with 7.2-mm edges, while the second comprises 1 639 146 cubic voxels with 3.6-mm edges. Calculations on the lower-resolution model using, for example, the finite difference time domain or impedance methods, push the capabilities of workstations. The scalar method, in contrast, can handle the higher-resolution model using comparable resources. The results are given in terms of average and maximum electric field intensities and current density magnitudes in selected tissues and organs. Although the lower-resolution model provides generally acceptable results, there are important differences that make the added computational burden of the higher-resolution calculations worthwhile. In particular, the higher-resolution modelling generally predicts peak electric fields intensities and current density magnitudes that are slightly higher than those computed using the lower-resolution modelling. The differences can be quite large for small organs such as glands. Bioelectromagnetics 18:478-490, 1997. © 1997 Wiley-Liss, Inc.
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    Bioelectromagnetics 18 (1997), S. 531-540 
    ISSN: 0197-8462
    Keywords: carcinogenicity ; rat ; magnetic field ; elf ; two-year bioassay ; lifetime exposures ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Male and female F344 rats, 48 per exposure group, were sham exposed (Group A) or exposed to 0.5 (Group B) and 5 mT (Group C) magnetic fields for two years. Animals were exposed from 5-109 weeks of age in SPF conditions according to the OECD test guideline No. 451. Average exposure was 22.6 hr/day. No significant differences in body weight and food consumption were observed between the sham and exposed groups. At the end of the exposure period, survival rates of the male rats were 73, 83, and 79%, and those of the females, 77, 79, and 75% for Groups A, B, and C, respectively, with no significant differences between groups. Differential counts of leukocytes were measured at the 52nd, 78th, and 104th weeks of exposure and no significant differences were observed between the exposure groups. All survivors were euthanized on schedule, and all the organs and tissues suspected of tumoral lesions were examined histopathologically. Incidences of mononuclear cell leukemia in the male and the female rats were 5, 4, 4 and 8, 6, 7 for Groups A, B and C, respectively; incidences of malignant lymphoma in the female rats were 0, 1 and 1. Neither significant increases nor acceleration of incidence of leukemia were observed. Incidences of brain and intracranial tumors did not increase in the exposed groups. Incidences of both benign and malignant neoplasms showed no significant difference between the exposed and sham exposed groups with one exception: fibroma of the subcutis in the male rats, which was considered not to be a statistically significant when evaluated with respect to the historical control data in our laboratory. Bioelectromagnetics 18:531-540, 1997. © Wiley-Liss, Inc.
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    Bioelectromagnetics 18 (1997), S. 273-276 
    ISSN: 0197-8462
    Keywords: coil probe ; dipole field ; magnetic field ; measurement uncertainty ; power frequency ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Comparisons are made between the average magnetic flux density as it would be measured with a single-axis coil probe and the flux density at the center of the probe, assuming that the probe is oriented to measure the maximum field at that point. Probability distributions of the differences between the two quantities are calculated assuming a dipole magnetic field and are found to be asymmetric. The distributions are used to estimate the uncertainty for maximum magnetic field measurements at distances that are large compared with the dimensions of the field source. Bioelectromagnetics 18:273-276, 1997. © 1997 Wiley-Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.
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  • 50
    ISSN: 0197-8462
    Keywords: amino acids ; electromagnetic fields ; high-pressure liquid chromatography ; neurochemistry ; radiofrequency radiation ; thermoregulation ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Exposure to radiofrequency radiation (RFR) may produce thermal responses. Extracellular amino acid concentrations in the hypothalamus (Hyp) and caudate nucleus (CN) were measured by using in vivo microdialysis before and during exposure to RFR. Under urethane anesthetic, each rat was implanted stereotaxically with a nonmetallic microdialysis probe and temperature probe guides and then placed in the exposure chamber. The rat laid on its right side with its head and neck placed directly under the wave guide. Temperature probes were placed in the left brain, right brain, face (subcutaneously), left tympanum, and rectum. Each microdialysis sample was collected over a 20 min period. The microdialysis probe was perfused for 2 h before the rat was exposed to 5.02 GHz radiation (10 μs pulse width, 1000 pulses/s). The right and left sides of the brain were maintained at approximately 41.2 and 41.7 °C, respectively, throughout a 40 min exposure period. Initially when the brain was being heated to these temperatures, the time-averaged specific absorption rates (SARs) for the right and left sides of the brain were 29 and 40 W/kg, respectively. Concentrations of aspartic acid, glutamic acid, serine, glutamine, and glycine in dialysate were determined by using high-pressure liquid chromatography with electrochemical detection. In the Hyp and CN, the concentrations of aspartic acid, serine, and glycine increased significantly during RFR exposure (P 〈 .05). These results indicate that RFR-induced thermal stress produces a general change in the amino acid concentrations that is not restricted to thermoregulatory centers. Changes in the concentrations of glutamic acid (Hyp, P = .16; CN, P = .34) and glutamine (Hyp, P = .13; CN, P = .10) were not statistically significant. Altered amino acid concentrations may reveal which brain regions are susceptible to damage in response to RFR-induced thermal stress. Bioelectromagnetics 18:277-283, 1997. © 1997 Wiley-Liss, Inc.
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    Bioelectromagnetics 18 (1997), S. 335-338 
    ISSN: 0197-8462
    Keywords: radiofrequency radiation ; heart rate ; blood pressure ; cardiovascular system ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: These experiments were designed to investigate the effects of sub-resonant microwave (MW) exposure (350 MHz, E orientation, average power density 38 mW/cm2, average whole-body specific absorption rate 13.2 W/kg) on selected physiological parameters. The increase in peripheral body temperature during 350 MHz exposure was greater than that in earlier experiments performed at 700 MHz (resonance). Heart rate and mean arterial blood pressure were significantly elevated during a 1 °C increase in colonic temperature due to 350 MHz exposure; respiratory rate showed no significant change. The results are consistent with other investigators' reports comparing sub-resonance exposures with those at resonance and above. Bioelectromagnetics 18:335-338, 1997. © 1997 Wiley-Liss, Inc.
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    Bioelectromagnetics 18 (1997), S. 307-316 
    ISSN: 0197-8462
    Keywords: residential magnetic fields ; power net currents ; ground currents ; water lines ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: The magnetic fields from power-frequency current flowing on water lines were investigated in a new approach that involved an area-wide survey in a small town. Magnetic fields were measured outside the residence under power cables and over water lines, and each residence was characterized as to whether it received water from a private well or the municipal water system. The magnetic field data revealed two statistical modes when they were related to water supply type. The data also showed that in the case of the high mode, the magnetic field remained constant along the line formed by power drop wires, at the back of the house, and the water hookup service, in front of the house, all the way to the street. The patterns are explained by the coincidence of measurement points and the presence of net current flowing on power mains, power drop conductors, residential plumbing, water service hookups, and water mains. These patterns, together with other characteristics of this magnetic field source, such as the gradual spatial fall-off of this field and the presence of a constant component in the time sequence, portray a magnetic field more uniform and constant in the residential environment than has been thought to exist. Such characteristics make up for the weakness of the source and make net current a significant source of exposure in the lives of individuals around the house, when human exposure to magnetic fields is assumed to be a cumulative effect over time. This, together with the bimodal statistical distribution of the residential magnetic field (related to water supply type), presents opportunities for retrospective epidemiological analysis. Water line type and its ability to conduct power-frequency current can be used as the historical marker for a bimodal exposure inference, as Wertheimer et al. have shown. Bioelectromagnetics 18:307-316, 1997. © 1997 Wiley-Liss, Inc.
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    BioEssays 19 (1997) 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
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    BioEssays 19 (1997), S. 13-21 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Mos, a protein kinase, is specifically expressed and functions during meiotic maturation (or G2/M progression) of vertebrate oocytes. When expressed ectopically, however, it can also readily induce oncogenic transformation (or uncontrolled G1/S transitions) in somatic cells. In both of these cell types, Mos activates mitogen-activated protein kinase (MAPK), which seems largely to mediate its different functions in both oocyte maturation and cellular transformation. In oocyte maturation, the Mos-MAPK pathway probably serves to activate and stabilize M-phase promoting factor (MPF) (possibly by inhibiting some negative regulator(s) of this factor), while in cellular transformation, it seems to stabilize and activate the nuclear oncoprotein c-Fos as well as to induce transcription of its gene. Thus, the different functions of Mos in oocytes and somatic cells may arise chiefly from its different MAPK-mediated targets in the respective cell types. This review discusses the cellular basis that may enable Mos to act differently in oocytes and somatic cells.
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    BioEssays 19 (1997), S. 23-28 
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    Notes: One distinguishing feature of vertebrate oocyte meiosis is its discontinuity; oocytes are released from their prophase I arrest, usually by hormonal stimulation, only to again halt at metaphase II, where they await fertilization. The product of the c-mos proto-oncogene, Mos, is a key regulator of this maturation process. Mos is a serine-threonine kinase that activates and/or stabilizes maturation-promoting factor (MPF), the master cell cycle switch, through a pathway that involves the mitogen-activated protein kinase (MAPK) cascade. Oocytes arrested at prophase I lack detectable levels of Mos, which must be synthesized from a pool of maternal mRNAs for proper maturation. While Mos is necessary throughout maturation in Xenopus, it seems to be required only for meiosis II in the mouse. The translational activation of c-mos mRNA at specific times during meiosis requires cytoplasmic polyadenylation. Cis- and trans-acting factors for polyadenylation are, therefore, essential elements of maturation.
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    BioEssays 19 (1997), S. 29-36 
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    Notes: Oocytes, eggs and blastomeres of the embryo are special cells that undergo rapid changes in structure and function at developmental transitions. These changes are frequently regulated by cytoplasmic signaling events, particularly at the developmental transition of fertilization, because the genome is largely inactivated at this time. Protein kinase C (PKC) is a signaling agent that acts after the sperm-induced rise in calcium and has a central role in the remodeling of the structure of the egg into the zygote in many species. PKC also acts during other developmental transitions. This kinase serves as a chronometer, which can choreograph the cell's remodeling events in both space and time. Several technical advancements discussed in this review have permitted a better understanding of the actions of PKC.
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    BioEssays 19 (1997), S. 37-46 
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    Notes: Ever since it was discovered in hydra, regeneration has remained a stimulating question for developmental biologists. Cellular approaches have revealed that, within the first few hours of apical or basal hydra regeneration, differentiation and determination of nerve cells are the primary cellular events detectable. The head and foot activators (HA, FA), neuropeptides that are released upon injury, are signaling molecules involved in these processes. In conditions where it induces cellular differentiation or determination, HA behaves as an agonist of the cyclic AMP (cAMP) pathway involving the modulation of CREB nuclear transcription factor activity. This cascade would be required for proper regeneration, regardless of whether the polarity involved is apical or basal. Modulations of the protein kinase C pathway, which have been shown to affect apical or basal positional values, might signal to bring about this polarity; however, endogenous ligands responsible for this modulation are as yet unknown.
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    BioEssays 19 (1997), S. 47-55 
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    Notes: Integrins are ubiquitous trans-membrane adhesion molecules that mediate the interaction of cells with the extracellular matrix (ECM). Integrins link cells to the ECM by interacting with the cell cytoskeleton. In cases such as leukocyte binding, integrins mediate cell-cell interactions and cell-ECM interactions. Recent research indicates that integrins also function as signal transduction receptors, triggering a number of intracellular signaling pathways that regulate cell behavior and development. A number of integrins are known to stimulate changes in intracellular calcium levels, resulting in integrin activation. Although changes in intracellular calcium regulate a vast number of cellular functions, this review will discuss the stimulation of calcium signaling by integrins and the role of intracellular calcium in the regulation of integrin-mediated adhesion.
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    BioEssays 19 (1997), S. 57-66 
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    Notes: Peroxisomes are eukaryotic organelles that are the subcellular location of important metabolic reactions. In humans, defects in the organelle's function are often lethal. Yet, relative to other organelles, little is known about how cells maintain and propagate peroxisomes or how they direct specific sets of newly synthesized proteins to these organelles (peroxisome biogenesis/assembly). In recent years, substantial progress has been made in elucidating aspects of peroxisome biogenesis and in identifying PEX genes whose products, peroxins, are essential for one or more of these processes. The most progress has been made in understanding the mechanism by which peroxisome matrix proteins are imported into the organelles. Signal sequences responsible for targeting proteins to the organelle have been defined. Potential signal receptor proteins, a receptor docking protein and other components of the import machinery have been identified, along with insights into how they operate. These studies indicate that multiple peroxisomal protein-import mechanisms exist and that these mechanisms are novel, not simply variations of those described for other organelles.
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    BioEssays 19 (1997), S. 67-74 
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    Notes: Immunofluorescent labelling demonstrates that human metaphase chromosomes contain hyperacetylated histone H4. With the exception of the inactive X chromosome in female cells, where the bulk of histone H4 is under-acetylated, H4 hyperacetylation is non-uniformly distributed along the chromosomes and clustered in cytologically resolvable chromatin domains that correspond, in general, with the R-bands of conventional staining. The strongest immunolabelling is often found in T-bands, the subset of intense R-bands having the highest GC content. The majority of mapped genes also occurs in R-band regions, with the highest gene density in T-bands. These observations are consistent with a model in which hyperacetylation of histone H4 marks the position of potentially active gene sequences on metaphase chromosomes. Since acetylation is maintained during mitosis, progeny cells receive an imprint of the histone H4 acetylation pattern that was present on the parental chromosomes before cell division. Histone acetylation could provide a mechanism for propagating cell memory, defined as the maintenance of committed states of gene expression through cell lineages.
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    BioEssays 19 (1997), S. 85-86 
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    BioEssays 19 (1997), S. 92-93 
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    BioEssays 19 (1997), S. 95-96 
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    BioEssays 19 (1997), S. 101-104 
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    Notes: The Wnt signalling cascade is a highly conserved signalling pathway throughout the animal kingdom. In Xenopus, Wnt signalling functions in mesodermal dorsoventral patterning. Earlier work on deciphering the components of the wnt signalling cascade left a gap between cytosolic β-catenin, the final member of the cascade, and the nuclear target genes. Several recent papers now reveal how the Wnt signal is transmitted into the nucleus. Surprisingly, β-catenin directly interacts with the transcription factor LEF-1/XTCF-3, and thereby is not only translocated into the nucleus but also modulates the properties of LEF-1/XTCF-3 as a transcription factor(1-5).
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    BioEssays 19 (1997), S. 105-116 
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    Notes: Axis specification is the first step in defining specific regions of the developing embryo. Embryos exploit asymmetries, either pre-existing in the egg or triggered by external cues, to establish embryonic axes. The axial information is then used to generate regional differences within the embryo. In this review, we discuss experiments in animals which address three questions: whether the unfertilized egg is constructed with pre-determined axes, what cues are used to specify the embryonic axes, and how these cues are interpreted to generate the initial regional differences within the embryo. Based on mapping the data onto an animal phylogeny, we then propose a scenario for how this primary developmental decision occurred in ancestral metazoans.
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    BioEssays 19 (1997), S. 97-99 
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    Notes: DNA topoisomerase II (topo II) is involved in chromosome structure and function, although its exact location and role in mitosis are somewhat controversial. This is due in part to the varied reports of its localization on mitotic chromosomes, which has been described at different times as uniformly distributed, axial on the chromosome arms and predominantly centromeric. These disparate results are probably due to several factors, including use of different preparation and fixation techniques, species differences and changes in distribution during the cell cycle. Recently, several papers have re-investigated the distribution of topo II on chromosomes as a function of cell cycle and species(1-3). The new studies suggest that Topo II has a dynamic pattern of distribution on the chromosomes, in general becoming axial as chromosomes condense during prophase and then concentrating at centromeres during metaphase. These experiments suggest a novel role for topo II in centromere structure and function.
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    BioEssays 19 (1997), S. 117-126 
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    Notes: Chloride channels are probably found in every cell, from bacteria to mammals. Their physiological tasks range from cell volume regulation to stabilization of the membrane potential, signal transduction, transepithelial transport and acidification of intracellular organelles. These different functions require the presence of many distinct chloride channels, which are differentially expressed and regulated by various stimuli. These include various intracellular messengers (like calcium and cyclic AMP), pH, extracellular ligands and transmembrane voltage. Three major structural classes of chloride channels are known to date, but there may be others not yet identified. After an overview of the general functions of chloride channels, this review will focus on these cloned chloride channels: the CLC chloride channel family, which includes voltage-gated chloride channels, and the cystic fibrosis transmembrane regulator (CFTR), which performs other functions in addition to being a chloride channel. Finally, a short section deals with GABA and glycine receptors. Diseases resulting from chloride channel defects will be specially emphasized, together with the somewhat limited information about how these proteins work at the molecular level.
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    BioEssays 19 (1997), S. 137-145 
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    Notes: Focal adhesion kinase (FAK) is a nonreceptor protein-tyrosine kinase implicated in controlling cellular responses to the engagement of cell-surface integrins, including cell spreading and migration, survival and proliferation. Aberrant FAK signaling may contribute to the process of cell transformation by certain oncoproteins, including v-Src. Progress toward elucidating the events leading to FAK activation following integrin-mediated cell adhesion, as well as events downstream of FAK, has come through the identification of FAK phosphorylation sites and interacting proteins. A signaling partnership is formed between FAK and Src-family kinases, leading to tyrosine phosphorylation of FAK and associated ‘docking’ proteins Cas and paxillin. Subsequent recruitment of proteins containing Src homology 2 domains, including Grb2 and c-Crk, to the complex is likely to trigger adhesion-induced cellular responses, including changes to the actin cytoskeleton and activation of the Ras-MAP kinase pathway.
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    BioEssays 19 (1997), S. 181-182 
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    BioEssays 19 (1997), S. 183-184 
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    BioEssays 19 (1997), S. 175-179 
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    Notes: Dr Ernst Mayr has been one of the seminal figures of 20th century biology. His essential contributions were in the development of the Modern Synthesis in evolutionary biology. His landmark book Systematics and the Origin of Species, was published in 1942 and has long been acknowledged as one of the key foundations of 20th century evolutionary biology. In many subsequent articles and books on evolution and the history and philosophy of biology during the past half century, he has continued to be a key contributor of ideas and inspiration to successive generations of evolutionary biologists.In the first of two ‘Roots’ articles, he describes the early stages of his career and the serendipitous events that furthered it. This article was first presented as a talk, on October 27, 1993, at the 50 year Jubilee celebration of the founding of the Whitney wing, the ornithological section, of the American Museum of Natural History in New York City. In next month's ‘Roots’ article, Dr Mayr will describe the events that led to the founding of the Society for the Study of Evolution in 1946, in St Louis, Missouri.
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    BioEssays 19 (1997), S. 167-173 
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    Notes: Chlorarachniophytes are amoeboflagellate, marine protists that have acquired photosynthetic capacity by engulfing and retaining a green alga. These green algal endosymbionts are severely reduced, retaining only the chloroplast, nucleus, cytoplasm and plasma membrane. The vestigial nucleus of the endosymbiont, called the nucleomorph, contains only three small linear chromosomes and has a haploid genome size of just 380 kb - the smallest eukaryotic genome known. Initial characterisation of nucleomorph DNA has revealed that all chromosomes are capped with inverted repeats comprising a telomere and a single ribosomal RNA operon. The nucleomorph genome is the quintessence of compactness; average space between genes is a mere 65 bp, some genes overlap, others are cotranscribed. Intense reductive pressures upon nucleomorph genes have apparently squeezed their spliceosomal-type introns down to only 18, 19 or 20 bases in length. Studies to date indicate the nucleomorph - essentially a stripped-down eukaryotic genome - encodes principally genetic housekeeping functions such as translation, transcription and splicing.
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    BioEssays 19 (1997), S. 185-185 
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    BioEssays 19 (1997), S. 184-184 
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    BioEssays 19 (1997), S. 281-284 
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    Notes: Genetic analysis of Drosophila has shown that a morphogenetic gradient of the Transforming Growth Factor-β family member dpp patterns the embryonic dorsalventral axis. Molecular and embryological evidence from Xenopus has strongly suggested a similar role for Bmp-4, the dpp homolog, in patterning the dorsalventral axis of chordates. A recent report has now identified mutations in two genes, dino and swirl, that disrupt dorsal-ventral patterning in the zebrafish Danio rerio(1). Characterization of these mutations parallels findings from Drosophila, thus establishing a genetic framework for the analysis of dorsalventral patterning in a vertebrate.
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    BioEssays 19 (1997), S. 287-296 
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    Notes: Embryonic development results in animals whose body plans exhibit a variety of symmetry types. While significant progress has been made in understanding the molecular events underlying the early specification of the antero-posterior and dorso-ventral axes, little information has been available regarding the basis for left-right (LR) differences in animal morphogenesis. Recently however, important advances have been made in uncovering the molecular mechanisms responsible for LR patterning. A number of genes (including well-known signaling molecules such as Sonic hedgehog and activin) are asymmetrically expressed in early chick embryos, well before the appearance of morphological asymmetries. One of these, nodal, is asymmetrically expressed in frogs and mice as well, and its expression is altered in mouse mutants exhibiting defects in laterality. In the chick, these genes regulate each other in a sequential cascade, which independently determines the situs of the heart and other organs.
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    BioEssays 19 (1997), S. 307-315 
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    Notes: Cyclin-dependent kinases and their regulatory subunits, the cyclins, are known to regulate progression through the cell cycle. Yet these same proteins are often expressed in non-cycling, differentiated cells. This review surveys the available information about cyclins and cyclin-dependent kinases in differentiated cells and explores the possibility that these proteins may have important functions that are independent of cell cycle regulation.
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    BioEssays 19 (1997), S. 297-305 
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    Notes: Intermediate filaments, which form the structural framework of both the cytoskeleton and the nuclear lamina in most eukaryotic cells, have been found to be highly dynamic structures. A continuous exchange of subunit proteins at the filament surface and a stabilisation of soluble subunits by chaperone-type proteins may modulate filament structure and plasticity. Recent studies on the cell cycle-dependent interaction of intermediate filaments with associated proteins, and a detailed analysis of intermediate filament phosphorylation in defined subcellular locations at various stages of mitosis, have brought new insights into the molecular mechanisms involved in the mitotic reorganisation of intermediate filaments. Some of these studies have allowed new speculations about the possible cellular functions of cytoplasmic intermediate filaments, and increased our understanding of the specific functions of the lamins and the lamina-associated membrane proteins in the post-mitotic reassembly of the nucleus.
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    BioEssays 19 (1997), S. 317-326 
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    Notes: Under the putative influence of dietary selection pressure, the subcellular distribution of alanine:glyoxylate aminotransferase 1 (AGT) has changed on many occasions during the evolution of mammals. Depending on the particular species, AGT can be found either in peroxisomes or mitochondria, or in both peroxisomes and mitochondria. This variable localization depends on the differential expression of N-terminal mitochondrial and C-terminal peroxisomal targeting sequences by the use of alternative transcription and translation initiation sites. AGT is peroxisomal in most humans, but it is mistargeted to the mitochondria in a subset of patients suffering from the rare herediatry disease primary hyperoxaluria type 1. Mistargeting is due to the unlikely combination of a normally occurring polymorphism that generates a functionally weak mitochondrial targeting sequence and a disease-specific mutation which, in combination with the polymorphism, inhibits AGT dimerization. The mechanisms by which AGT can be targeted differentially to peroxisomes and/or mitochondria highlight the different molecular requirements for protein import into these two organelles.
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    BioEssays 19 (1997), S. 327-335 
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    Notes: The molecular pathways for insulin's signal transduction from its cell surface receptor to the cell's interior metabolic machinery remain in many ways uncharted. Lately two molecules have been proposed as second messengers transducing the insulin signal into the target cell. One is a phospholigosaccharide/inositolphosphoglycan and the other is diacylglycerol, both deriving from the same plasma membrane glycolipid, which is hydrolysed in response to insulin treatment. The phospho-oligosaccharide appears to mediate many metabolic effects of insulin through control of the phosphorylation state of key regulatory metabolic enzymes. Diacylglycerol may mediate insulin's stimulation of glucose transport over the plasma membrane. The glycolipid precursor of these putative second messengers, as well as the receptor for insulin, appear to be localized in caveolae microdomains of the plasma membrane, and glucose transporters accumulate in caveolae in response to insulin treatment, suggesting a focal role for caveolae in insulin signalling.
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    BioEssays 19 (1997), S. 337-345 
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    Notes: How different neural crest derivatives differentiate in distinct embryonic locations in the vertebrate embryo is an intriguing issue. Many attempts have been made to understand the underlying mechanism of specific pathway choices made by migrating neural crest cells. In this speculative review we suggest a new mechanism for the regulation of neural crest cell migration patterns in avian and mammalian embryos, based on recent progress in understanding the expression and activity of receptor tyrosine kinases during embryogenesis. Distinct subpopulations of crest-derived cells express specific receptor tyrosine kinases while residing in a migration staging area. We postulate that the differential expression of receptor tyrosine kinases by specific subpopulations of neural crest cells allows them to respond to localized growth factor ligand activity in the embryo. Thus, the migration pathway taken by neural crest subpopulations is determined by their receptor tyrosine kinase response to the differential localization of their cognate ligand.
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    BioEssays 19 (1997), S. 359-359 
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    BioEssays 19 (1997), S. 353-358 
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    Notes: Pheromones play a curcial role in mate stimulation and discrimination. In the fruit fly Drosophila, the most abundant cuticular hydrocarbons act as sex pheromones during courtship behavior. There are several active molecules and they compose a sex- and species-specific pheromonal bouquet. Different species from the Drosophila melanogaster subgroup have adopted alternative systems of chemical mate recognition. Recent exploration of these interspecific variations, and of intraspecific variations, has led to the characterization of genes and to the mapping of structures that process the production and perception of chemical messages.
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    BioEssays 19 (1997), S. 359-360 
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    BioEssays 19 (1997), S. 367-370 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Transcription in organisms as diverse as yeast and mammals is subject to chromosomal position effects that result in heritable and variegated patterns of gene expression. Two recent studies have employed a reversible protein-DNA crosslinking method to identify the structural components of heterochromatin in budding yeast(1,2). The results show that a complex containing the proteins Rap1, Sir2p, Sir3p and Sir4p is physically associated with nucleosomes at telomere proximal regions, but that the repressive chromatin structure extended by Sir3p overexpression has a different composition.
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    BioEssays 19 (1997), S. 371-378 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: At fertilization in mammals the sperm activates the egg by triggering a series of oscillations in the intracellular free Ca2+ concentration. The precise sequence of events that occur between sperm-egg contact and the increases in intracellular Ca2+ remains unknown. Here, we discuss recent evidence supporting the hypothesis that a cytosolic sperm protein enters the egg after gamete membrane fusion and triggers Ca2+ oscillations from within the egg cytoplasm. Biochemical studies suggest that there exists a novel sperm protein, named oscillin, that specifically comigrates with Ca2+ oscillation-inducing activity. Oscillin has been immunolocalised to the region of the sperm that first fuses with the egg. The concept of a specific protein that triggers Ca2+ oscillations may have wider physiological significance since sperm oscillin can induce Ca2+ oscillations in somatic cells, such as neurons and hepatocytes. Unravelling the novel signalling system involved in mammalian fertilization may help reveal some fundamental molecular mechanisms responsible for triggering cytoplasmic Ca2+ oscillations.
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  • 89
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    BioEssays 19 (1997), S. 379-388 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Hox complex genes are key developmental regulators highly conserved throughout evolution. The encoded proteins share a 60-amino-acid DNA-binding motif, the homeodomain, and function as transcription factors to control axial patterning. An important question concerns the nature and function of genes acting downstream of Hox proteins. This review focuses on Drosophila, as little is known about this question in other organisms. The noticeable progress gained in the field during the past few years has significantly improved our current understanding of how Hox genes control diversified morphogenesis. Here we summarise the strategies deployed to identify Hox target genes and discuss how their function contributes to pattern formation and morphogenesis. The regulation of target genes is also considered with special emphasis on the mechanisms underlying the specificity of action of Hox proteins in the whole animal.
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  • 90
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    BioEssays 19 (1997), S. 389-395 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Hirschsprung disease and the multiple endocrine neoplasia type 2 syndromes are hereditary disorders related to the abnormal migration, proliferation or survival of neural crest cells and their derivatives. Hirschsprung disease is a frequent disorder of the enteric nervous system, resulting in intestinal obstruction. The multiple endocrine neoplasia type 2 syndromes predispose to cancers of neural crest derivatives. Both diseases are associated with heterozygous mutations in the RET proto-oncogene. RET encodes a transmembrane receptor tyrosine kinase expressed in neural crest lineages and whose ligand, glial-cell-line-derived neurotrophic factor, has been very recently identified. In vitro expression studies demonstrate that while Hirschsprung disease mutations result in loss of function of the mutant RET tyrosine kinase, multiple endocrine neoplasia type 2 mutations lead to its constitutive activation. Thus, the two ‘faces’ of RET, gain of function and loss of function, each lead to a different syndrome, respectively: multiple endocrine neoplasia type 2, a cancer syndrome, or Hirschsprung disease, a developmental defect.
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  • 91
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    BioEssays 19 (1997), S. 397-407 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The life cycle of Dictyostelium discoideum offers a unique opportunity to study signal transduction in eukaryotic cells at both the unicellular and multicellular levels of organization. Adding to the already extensive knowledge of the unicellular stages, classical and molecular genetics have begun to unravel transduction of signals controlling morphogenesis and behaviour (phototaxis and thermotaxis) in the multicellular ‘slug’ stage of the life cycle. Distributed over all seven genetic linkage groups are probably about 20, but possibly as many as 55, genes of importance for slug behaviour. The encoded proteins appear from pharmacological studies and mutant phenotypes to govern transduction pathways involving the intracellular second messengers cyclic AMP, cyclic GMP, IP3 and Ca2+. Pathways from the photo- and thermoreceptors converge first with each other and thence, at the level of the second messengers, with those from extracellular tip activation (cyclic AMP) and inhibition (Slug Turning Factor and/or ammonia and/or adenosine) signals that control slug movement and morphogenesis.
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  • 92
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    BioEssays 19 (1997), S. 501-507 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Interleukin 1β-converting enzyme (ICE)-like proteases (caspases) play an important role in programmed cell death (apoptosis), and elucidating the consequences of their proteolytic activity is central to our understanding of the molecular mechanisms of cell death. Diverse structural and regulatory proteins and enzymes, including protein kinase Cδ, the retinoblastoma protein (a protein involved in cell survival), the DNA repair enzyme DNA-dependent protein kinase and the nuclear lamins, undergo specific and limited endoproteolytic cleavage by various caspases during apoptosis. Since individual caspases can cleave multiple substrates, the consequences of cleavage of only a single substrate are still poorly understood. Nevertheless, proteolytic activation of protein kinase Cδ may be an important early step in the cell death pathway, and cleavage of the retinoblastoma protein could suppress its cell survival function, whereas proteolytic inactivation of DNA repair enzymes might compromise the ability of the cell to reverse DNA fragmentation. On the other hand, cleavages of nuclear and cytoplasmic structural proteins (e.g. the lamins and Gas2) appear to be required for or contribute to the dramatic rearrangements in cellular architecture that are necessary for the completion of the cell death process. An emerging theme is that parallel and sequential proteolytic activation and inactivation of key protein substrates occurs during the multiple steps of apoptosis.
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  • 93
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    BioEssays 19 (1997), S. 547-550 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: How do cells order their cytoplasm? While microtubule organizing centers have long been considered essential to conferring order by virtue of their microtubule nucleating activity, attention has currently refocused on the role that microtubule motors play in organizing microtubules. An intriguing set of recent findings(1) reveals that cell fragments, lacking microtubule organizing centers, rapidly organize microtubules into a radial array during organelle transport driven by the microtubule motor, cytoplasmic dynein. Further, interaction of radial microtubules with the cell surface centers the array, revealing that centering information resides not with centrosomes but with organized microtubules.
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  • 94
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    BioEssays 19 (1997), S. 551-555 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Homeobox genes play essential roles in specifying the fates of different cell types during embryogenesis. In Drosophila, the homeotic gene caudal is important for the generation of posterior structures. In the mouse, the caudal homologue Cdx2 has been implicated in directing early processes in intestinal morphogenesis and in the maintenance of the differentiated phenotype. A recent study showed that Cdx2 null mutation was embryonically lethal, whereas Cdx2+/- mice developed multiple intestinal polyps in the proximal colon in addition to developmental defects(1). There are striking phenotypic similarities and differences between Cdx2+/- and other mice predisposed to intestinal neoplasia. The possible role of Cdx2 in human colorectal tumorigenesis is discussed.
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  • 95
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    BioEssays 19 (1997), S. 557-559 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The telomere is a functional domain of the chromosome, located at the extreme ends, and is essential for normal chromosome stability. Chromosomes lacking telomeres are inherited improperly, and mutations in the telomeric repeat sequences are thought to lead to senescence and possibly to cancer. The molecular mechanisms maintaining chromosomes by telomeres, however, have been unclear. Results recently reported by Kirk et al.(1) offer an insight into new telomerase function. They have identified a novel telomerase mutation that blocks sister chromatid separation in mitosis.
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  • 96
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    BioEssays 19 (1997), S. 541-546 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Molecular and developmental studies of limb pattern formation have recently gained widespread attention. The fact that vertebrate limbs are amenable to both genetic and embryological manipulations has established this model system as a valuable paradigm for studying vertebrate development. Limb buds are polarised along all three major axes and the establishment of the dorso-ventral (DV) polarity is dependent upon cues localised in the trunk, where a DV ectodermal interface is produced by confrontation of dorsal and ventral identities. By analogy to Drosophila imaginal disc development, this interface has been proposed to determine and position an ectodermal organising centre, the Apical Ectodermal Ridge (AER), controlling limb bud outgrowth. Recent fate mapping studies(1) and studies of genes regulating DV limb polarity(2-6), AER formation(7,8) and differentiation(9) suggest, however, that DV patterning and AER induction, though coordinately regulated during limb bud outgrowth, may early on be more dissociated than expected.
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  • 97
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    BioEssays 19 (1997), S. 561-569 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Understanding how chemical energy is converted into directed movement is a fundamental problem in biology. In higher organisms this is accomplished through the hydrolysis of ATP by three families of motor proteins: myosin, dynein and kinesin. The most abundant of these is myosin, which operates against actin and plays a central role in muscle contraction. As summarized here, great progress has been made towards understanding the molecular basis of movement through the determination of the three-dimensional structures of myosin and actin and through the establishment of systems for site-directed mutagenesis of this motor protein. It now appears that the generation of movement is coupled to ATP hydrolysis by a series of domain movements within myosin.
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    BioEssays 19 (1997), S. 593-603 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The inositol phosphate metabolism network has been found to be much more complex than previously thought, as more and more inositol phosphates and their metabolizing enzymes have been discovered. Some of the inositol phosphates have been shown to have biological activities, but little is known about their signal transduction mechanisms except for that of inositol 1,4,5-trisphosphate. The recent discovery, however, of a number of binding proteins for inositol high polyphosphate [inositol 1,3,4,5-tetrakisphosphate (IP4), inositol 1,3,4,5,6-pentakisphosphate, or inositol hexakisphosphate] enables us to speculate on the physiological function of these compounds. In this article we focus on two major issues: (1) the roles of inositol high polyphosphates in vesicular trafficking, especially exocytosis, and (2) pleckstrin homology domaincontaining IP4 binding proteins involved in the Ras signaling pathway.
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    BioEssays 19 (1997), S. 657-660 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: A key characteristic of an animal's nervous system is that it can respond to brief environmental stimuli with lasting changes in its structure and function. These changes are triggered by specific patterns of neuronal electrical activity and are manifested as changes in the strength and patterns of synaptic connectivity between activated neurons. The biochemical mechanisms that control these changes are unclear, but cytoplasmic rises in Ca2+ levels may play a critical role, especially in regulating neuronal gene expression for making activity-induced synaptic changes permanent. Recently, two reports have explored the spatial features by which activity-induced rises in Ca2+ levels activate transcription factors and gene expression(1,2). The reports suggest that Ca2+ influx acts both locally at the synapse and distantly within the nucleus to regulate transcription factors and gene expression. The results also show that regulatory elements within genes can respond differentially, depending on spatial differences in intracellular Ca2+ rises. These reports suggest new spatial mechanisms by which Ca2+-dependent gene expression could contribute to activity-dependent synaptic changes.
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    BioEssays 19 (1997), S. 673-682 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Our understanding of epithelial development in Drosophila has been greatly improved in recent years. Two key regulators of epithelial polarity, Crumbs and DE-cadherin, have been studied at the genetic and molecular levels and a number of additional genes are being analyzed that contribute to the differentiation of epithelial cell structure. Epithelial architecture has a profound influence on morphogenetic movements, patterning and cell-type determination. The combination of embryological and genetic/molecular tools in Drosophila will help us to elucidate the complex events that determine epithelial cell structure and how they relate to morphogenesis and other developmental processes.
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