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  • Humans  (2,769)
  • United States  (716)
  • Mutation  (633)
  • Phosphorylation  (295)
  • Ultrastructure
  • American Association for the Advancement of Science (AAAS)  (3,569)
  • Springer  (175)
  • American Meteorological Society
  • MDPI - Multidisciplinary Digital Publishing Institute
  • MDPI Publishing
  • Protein Phosphorylation in Human Health
  • 1995-1999  (3,744)
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  • American Association for the Advancement of Science (AAAS)  (3,569)
  • Springer  (175)
  • American Meteorological Society
  • MDPI - Multidisciplinary Digital Publishing Institute
  • MDPI Publishing
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of the history of biology 32 (1999), S. 163-195 
    ISSN: 1573-0387
    Keywords: cytogenetics ; diagrams ; genetics ; illustrations ; McClintock ; models ; molecular biology ; photographs ; twentieth-century ; United States
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , History
    Notes: Abstract Barbara McClintock won the Nobel Prize in 1983 for her discovery of mobile genetic elements. Her Nobel work began in 1944, and by 1950 McClintock began presenting her work on “controlling elements.” McClintock performed her studies through the use of controlled breeding experiments with known mutant stocks, and read the action of controlling elements (transposons) in visible patterns of pigment and starch distribution. She taught close colleagues to “read” the patterns in her maize kernels, “seeing” pigment and starch genes turning on and off. McClintock illustrated her talks and papers on controlling elements or transposons with photographs of the spotted and streaked maize kernels which were both her evidence and the key to her explanations. Transposon action could be read in the patterns by the initiated, but those without step by step instruction by McClintock or experience in maize often found her presentations confusing. The photographs she displayed became both McClintock's means of communication, and a barrier to successful presentation of her results. The photographs also had a second and more subtle effect. As images of patterns arrived at through growth and development of the kernel, they highlight what McClintock believed to be the developmental consequences of transposition, which in McClintock's view was her central contribution, over the mechanism of transposition, for which she was eventually recognized by others. Scientific activities are extremely visual, both at the sites of investigation and in communication through drawings, photographs, and movies. Those visual messages deserve greater scrutiny by historians of science.
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  • 2
    ISSN: 1432-041X
    Keywords: Key words Imaginal disc ; Axonal trajectories ; Ultrastructure ; Chaoborus (Insecta ; Diptera)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  In one of his classical studies on insect metamorphosis, Weismann compared the imaginal anlagen of the ancestral phantom midge, Chaoborus, with those of advanced brachycerans. We have expanded his findings on the relationships between larval and imaginal organs using electron microscopy and cobalt backfilling of the antenna and leg anlagen and the axonal trajectories of corresponding larval sensilla. We show that both primordia are confluent with the larval antennae and ”leg” sensilla (an ancestral Keilin organ), respectively. These fully developed larval organs represent the distal tips of the imaginal anlagen rather than separate cell clusters. The axons of the larval antenna and leg sensilla project across the corresponding anlagen to their target neuromeres within the central nervous system (CNS). Within the discs, nerves composed of these larval axons, developing afferent fibres and efferences ascending from the CNS are found. Both the structure of the primordia and the axonal trajectories thus relate the situation found in advanced brachycerans with that seen in more ancestral insects. In addition, the larval antennae, legs, wings and even the eyes possess very similar afferent pioneer trajectories supporting the idea that the described pattern is generally used in the ontogeny of sensory systems.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Development genes and evolution 209 (1999), S. 427-431 
    ISSN: 1432-041X
    Keywords: Key words Drosophila ; Fushi tarazu ; Homeodomain ; Phosphorylation ; Neurogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  The homeodomain protein Fushi tarazu (Ftz) is required for several embryonic patterning processes including segmentation and neurogenesis. During the stages that these processes are regulated the protein is differentially phosphorylated, suggesting that phosphorylation plays a role in helping the protein to regulate different functions in different tissues. We showed in a recent study that one of the Ftz phosphorylation sites, a protein kinase A-type site in the N-terminal arm of the homeodomain, is required for normal Ftz-dependent segmentation. Here we test whether phosphorylation of this site (Thr-263) is also required in the developing central nervous system (CNS). A well-established role for Ftz in the CNS is for the differentiation of neurons referred to as RP2 neurons. Absence of Ftz expression in these cells causes a failure of certain target genes to be expressed and subsequent defects in RP2 differentiation. In contrast to its effect on segmentation, we find that mutation of Thr-263 to Ala (or Asp) has no effect on these CNS functions. This suggests that the phosphorylation state of this site is irrelevant for Ftz function in the CNS, and that there are tissue-specific differences in the requirements for Ftz phosphorylation.
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  • 4
    ISSN: 1423-0127
    Keywords: Tax ; HTLV-1 ; Trans-activation ; Phosphorylation ; Mutagenesis ; Transcription ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The human T cell leukemia virus type 1 (HTLV-1) Tax is a phosphoprotein, however, the contribution of phosphorylation to Tax activity is unknown. Previous studies have shown that phosphorylation of Tax occurs on serine residue(s), within one tryptic fragment, in response to 4β-phorbol-12β-myristate-13α-acetate, in both mouse and human cells. Studies were conducted in multiple cell lines to identify the specific phosphorylated serines as a prelude to functional analysis. The phosphorylation pattern of Tax was found to be different in 293T and COS-7 cells in comparison with MT-4 and Px-1 cells. However, one tryptic fragment remained consistent in comigration analyses among all cell lines. Using selected Tax serine mutants a tryptic fragment containing a serine at residue 113 believed to be the site of phosphorylation of Tax did not comigrate with the common phosphorylated tryptic fragment. Analysis of selected Tax mutants for ability totrans-activate the cytomegalovirus promoter demonstrated mutation of serine 77 to alanine reducedtrans-activation by 90% compared to wild-type Tax. However, examination of the phosphorylation pattern of the serine 77 mutant demonstrated that it is not the site of phosphorylation. These studies demonstrate the importance of using relevant cell lines to characterize the role of phosphorylation in protein function.
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  • 5
    ISSN: 1432-1211
    Keywords: Key words Llama ; splice ; CH1 ; Antibody ; Mutation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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  • 6
    ISSN: 1432-1211
    Keywords: Key words HLA complex ; Immotile cilia syndrome ; Mutation ; Kinesin multigene family ; Human Chromosome 6
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The kinesin-related protein (HSET) gene belongs to the kinesin superfamily, the members of which are involved in cellular transport processes. The HSET gene product was previously characterized by partial cDNA sequencing. The gene is located on the short arm of human Chromosome 6 (6p21.3), at the centromeric end of the major histocompatibility complex. Here, we report the genomic structure of the complete HSET gene together with its flanking loci. Sequence analysis of the 40 kilobase (kb) cosmid clone containing the HSET gene also revealed the presence of several new genes not related to the kinesin superfamily. These include a 60S ribosomal protein L35A-like pseudogene (rPL35A-like) on the telomeric side and a polycomb-like gene (PHF1), a copper tolerance-like gene (CUTA1) and the 5' part of the synaptic ras-GTPase-activating protein (SynGAP) gene centromeric of HSET. In addition, a complete 60S ribosomal protein L12-like (rPL12L) gene in intron 3 of the HSET gene was identified which appears to have an open reading frame. The possible involvement of the HSET gene and a β-tubulin gene (TUBB) in the pathogenesis of immotile cilia syndrome (ICS) was studied by screening two unrelated ICS families with microtubular defects and suspected HLA linkage for mutations within the HSET gene and the TUBB gene. Four single base substitutions were detected in the HSET gene, and none in the TUBB gene. On the basis of these data, a role of the HSET and TUBB products in the pathogenesis of ICS in the two families is unlikely.
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  • 7
    Electronic Resource
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    Springer
    Sexual plant reproduction 12 (1999), S. 99-109 
    ISSN: 1432-2145
    Keywords: Key words Arabidopsis thaliana ; Megasporogenesis ; Meiosis ; Ultrastructure ; Cellular polarity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  In this study, megasporogenesis of the plant model Arabidopsis thaliana was investigated by electron microscopy for the first time. The data described here could constitute a reference for future investigations of Arabidopsis mutants. During the beginning of meiosis the megaspore mother cell shows a polarity created by unequal distribution of organelles in the cytoplasm. Plastids accumulate in the chalazal region and long parallel saccules of endoplasmic reticulum, small vacuoles and some dictyosomes are found in the micropylar region. Plasmodesmata are abundant in the chalazal cell wall. The nucleus is almost centrally localized and contains a prominent excentric nucleolus and numerous typical synaptonemal complexes. After the second division of meiosis the four megaspores are separated by thin cell walls crossed by numerous plasmodesmata and do not show significant cellular organization. The young functional megaspore is characterized by a large nucleus and a large granular nucleolus. The cytoplasm is very electron dense due to the abundance of free ribosomes and contains the following randomly distributed organelles: mitochondria, a few short saccules of endoplasmic reticulum, dictyosomes and undifferentiated plastids. However, there is no apparent polarity, except for the distribution of some small vacuoles which are more abundant in the micropylar region of the cell. The degenerating megaspores are extremely electron dense and do not show any substructure.
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  • 8
    Electronic Resource
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    Springer
    Current genetics 35 (1999), S. 631-637 
    ISSN: 1432-0983
    Keywords: Key words Recombinator ; Meiotic recombination ; Polymorphism ; Mutation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The recombination hotspot cog overlaps a highly polymorphic 950-bp region of linkage group I in Neurospora crassa. The sequence of this region in the four strains, Lindegren 25a, Lindegren A, Emerson A and St. Lawrence 74A, each differs from the others by 1.4% or more. Comparison of the sequence of St. Lawrence 74A and Lindegren 25a each side of cog shows a high level of sequence heterology extending in both directions, including the coding sequences for his-3 and a putative gene lpl with homology to yeast lysophospholipase. The St. Lawrence 74A and Lindegren 25a sequences of his-3, centromere-proximal to cog, differ at 14 nucleotides, resulting in six amino-acid variations between the predicted protein sequences. In lpl, distal from cog, the sequences differ at 19 nucleotides leading to five amino-acid differences between the predicted proteins. Sequence heterology between St. Lawrence 74A and Lindegren 25a peaks either side of cog and then declines with distance. At the am locus on linkage group V, heterology is much less but peaks close to a weak recombination hotspot 5′ of the coding sequence. Uneven distribution of polymorphism along chromosomes has been explained by a hitch-hiking hypothesis in which selection for advantageous mutations causes local fixation of unselected variation. We suggest that new mutations arising from errors in recombination also contribute to the uneven distribution of polymorphism.
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  • 9
    ISSN: 1432-072X
    Keywords: Key wordsClostridium xylanolyticum ; Cinnamic acid ; Esterase ; Lignocellulose ; Sporogenesis ; Ultrastructure ; Cell envelope
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Microorganisms that hydrolyse the ester linkages between phenolic acids and polysaccharides in plant cell walls are potential sources of enzymes for the degradation of lignocellulosic waste. An anaerobic, mesophilic, spore-forming, xylanolytic bacterium with high hydroxy cinnamic acid esterase activity was isolated from the gut of the grass-eating termite Tumilitermes pastinator. The bacterium was motile and rod-shaped, stained gram-positive, had an eight-layered cell envelope, and formed endospores. Phylogenetic analysis based on 16S rRNA indicated that the bacterium is closely related to Clostridium xylanolyticum and is grouped with polysaccharolytic strains of clostridia. A wide range of carbohydrates were fermented, and growth was stimulated by either xylan or cellobiose as substrates. The bacterium hydrolysed and then hydrogenated the hydroxy cinnamic acids (ferulic and p-coumaric acids), which are esterified to arabinoxylan in plant cell walls. Three cytoplasmic enzymes with hydroxy cinnamic acid esterase activity were identified using non-denaturing gel electrophoresis. This bacterium possesses an unusual multilayered cell envelope in which both leaflets of the cytoplasmic membrane, the peptidoglycan layer and the S layer are clearly discernible. The fate of all these components was easily followed throughout the endospore formation process. The peptidoglycan component persisted during the entire morphogenesis. It was seen to enter the septum and to pass with the engulfing membranes to surround the prespore. It eventually expanded to form the cortex, verification for the peptidoglycan origin of the cortex. Sporogenic vesicles, which are derived from the cell wall peptidoglycan, were associated with the engulfment process. Spore coat fragments appeared early, in stage II, though spore coat formation was not complete until after cortex formation.
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  • 10
    ISSN: 1432-2242
    Keywords: Key words Brassica ; TuMV Resistance ; Genetic mapping ; Mutation ; Plant breeding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  Turnip mosaic virus (TuMV) is the major virus infecting Brassica crops. A dominant gene, TuRB01, that confers extreme resistance to some isolates of TuMV on Brassica napus (oilseed rape), has been mapped genetically. The mapping employed a set of doubled-haploid lines extracted from a population used previously to develop a reference RFLP map of the B. napus genome. The positioning of TuRB01 on linkage group N6 of the B. napus A–genome indicated that the gene probably originated from Brassica rapa. Resistance phenotypes were confirmed by indirect plate-trapped antigen ELISA using a monoclonal antibody raised against TuMV. The specificity of TuRB01 was determined using a wide range of TuMV isolates, including representatives of the European and American/Taiwanese pathotyping systems. Some isolates of TuMV that did not normally infect B. napus plants possessing TuRB01 produced mutant viruses able to overcome the action of the resistance gene. TuRB01 is the first gene for host resistance to TuMV to be mapped in a Brassica crop. A second locus, TuRB02, that appeared to control the degree of susceptibility to the TuMV isolate CHN 1 in a quantitative manner, was identified on the C-genome linkage group N14. The mapping of other complementary genes and the selective combining of such genes, using marker-assisted breeding, will make durable resistance to TuMV a realisable breeding objective.
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  • 11
    ISSN: 1432-0878
    Keywords: Key words Chondrocyte ; Synoviocyte ; Co-culture ; Proliferation ; Lipid peroxidation ; Cytotoxicity ; Ultrastructure ; Rat (Wistar)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Objective: A new co-culture system of rat articular chondrocytes and synoviocytes (HIG-82; cell line) was incubated with phorbol myristate acetate (PMA), H2O2 or a combination of Fe2+ and ascorbic acid to simulate inflammation-like radical attacks in articular joints. Methods: Chondrocytes were characterized by immunocytochemistry against collagen type II, transmission electron (TEM) and light microscopy. Lipid peroxidation was investigated by measuring thiobarbituric-acid-reactive material in the supernatants, cytotoxicity by determining release of lactate dehydrogenase and proliferation by measuring [3H]thymidine incorporation, culture protein and DNA. Results: PMA or Fe2+ and ascorbic acid induced lipid peroxidation in chondrocytes and synoviocytes that was decreased significantly in co-cultures. PMA and H2O2 dose dependently induced release of lactate dehydrogenase in chondrocytes, which was lowered in co-cultures or in previously co-cultured chondrocytes to a nearly basal level. In contrast, conditioned media of synoviocyte cultures showed no lowering effect on the radical-induced toxicity. Protection against H2O2-induced damage of cellular membranes by co-culturing was also shown by TEM. Synoviocytes released chondrocyte-stimulating growth factors spontaneously without previous interaction. Conclusion: Chondrocytes establish protective mechanisms against reactive oxygen species via an interaction with synoviocytes. Our co-culture model presents a possible way to study mechanisms of inflammation in articular joints under defined conditions.
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  • 12
    ISSN: 1432-0878
    Keywords: Key words Chloride cells (mitochondria-rich cells) ; Teleost larvae ; Osmoregulation ; Immunohistochemistry ; Quantification ; Ultrastructure ; Oreochromis mossambicus (Teleostei)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Integumental and branchial chloride cells of tilapia larvae (Oreochromis mossambicus) were studied at the light-microscopical and ultrastructural level. Total numbers and distribution of chloride cells were quantified after immunostaining of cross sections of the entire larvae with an antibody against the α-subunit of Na+/K+-ATPase. The majority (66%) of Na+/K+-ATPase-immunoreactive (ir) cells, i.e. chloride cells, of freshwater tilapia larvae were located extrabranchially up to 48 h after hatching. Five days after hatching, the majority (80%) of chloride cells were found in the buccal cavity. Transfer of 24-h-old larvae to 20% sea water speeded up this process; 24 h after transfer (i.e. 48 h after hatching), the majority (59%) of chloride cells were located in the buccal cavity. The branchial chloride cell population of 24-h- and 120-h-old larvae consisted of immature, mature, apoptotic and necrotic chloride cells. However, relatively more immature chloride cells were observed in freshwater larvae (42–63%) than in (previously studied) freshwater adults (21%), illustrating the developmental state of the gills. After transfer to sea water, the incidence of degenerative chloride cells did not change. Furthermore, the incidence of immature cells had decreased and a new subtype of chloride cells, the ”mitochondria-poor” cells, appeared more frequently. These mitochondria-poor chloride cells were characterised by an abundant tubular system and relatively few mitochondria, which were aligned at the border or concentrated in one part of the cytoplasm. Most of these cells did not contact the water. The function of their enhanced appearance after seawater transfer is unknown.
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  • 13
    ISSN: 1432-0878
    Keywords: Key words Mechanoreceptors ; Synaptic proteins ; Histochemistry ; Ultrastructure ; Slit sensilla ; Hair sensilla ; Cupiennius salei (Chelicerata)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Indirect immunocytochemical tests were used at the light- and electron-microscopic levels to investigate peripheral chemical synapses in identified sensory neurons of two types of cuticular mechanosensors in the spider Cupiennius salei Keys.: (1) in the lyriform slit-sense organ VS-3 (comprising 7–8 cuticular slits, each innervated by 2 bipolar sensory neurons) and (2) in tactile hair sensilla (each supplied with 3 bipolar sensory cells). All these neurons are mechanosensitive. Application of a monoclonal antibody against Drosophila synapsin revealed clear punctate immunofluorescence in whole-mount preparations of both mechanoreceptor types. The size and overall distribution of immunoreactive puncta suggested that these were labeled presynaptic sites. Immunofluorescent puncta were 0.5–6.8 μm long and located 0.5–6.6 μm apart from each other. They were concentrated at the initial axon segments of the sensory neurons, while the somata and the dendritic regions showed fewer puncta. Western blot analysis with the same synapsin antibody against samples of spider sensory hypodermis and against samples from the central nervous system revealed a characteristic doublet band at 72 kDa and 75 kDa, corresponding to the apparent molecular mass of synapsin in Drosophila and in mammals. Conventional transmissionelectron-microscopic staining demonstrated that numerous chemical synapses (with at least 2 vesicle types) were present at these mechanosensory neurons and their surrounding glial sheath. The distribution of these synapses corresponded to our immunofluorescence results.Ultrastructural examination of anti-synapsin-stained neurons confirmed that reaction product was associated with synaptic vesicles. We assume that the peripheral synaptic contacts originate from efferents that could exert a complex modulatory influence on mechanosensory activity.
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  • 14
    ISSN: 1432-0878
    Keywords: Key words Teleost fish ; Puberty ; Testes ; Sex steroids ; Ultrastructure ; Steroidogenesis ; Clarias gariepinus (Teleostei)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The present report focuses on the mechanism(s) involved in the steroid-induced decrease of androgen production in immature African catfish testes that was observed in previous studies. Juvenile animals were implanted with Silastic pellets containing different 11-oxygenated androgens (11-ketotestosterone, KT; 11β- hydroxyandrostenedione, OHA; 11-ketoandrostenedione, KA), testosterone (T) or estradiol-17β (E2). Control groups received steroid-free pellets. Two weeks later, testis tissue fragments were either incubated with increasing concentrations of catfish luteinizing hormone (LH), or incubated with [3H]-pregnenolone ([3H]-P5) or [3H]-androstenedione ([3H]-A). Tissue fragments were also prepared for the quantitative assessment of Leydig cell morphology. Most of the parameters studied were not affected significantly by implantation of E2. Implantation of all androgens inhibited both the basal and the LH-stimulated androgen secretory capacity in vitro. This was associated with a reduced size of the Leydig cells and loss of half of their mitochondria. The studies on the metabolism of tritiated steroid hormones indicated that steroidogenic steps prior to 11β-hydroxylation, probably C17–20 lyase activity, were affected by all androgens. Although the effects of 11-oxygenated androgens and T on Leydig cells were mostly similar, previous work showed that only the 11-oxygenated androgens stimulated spermatogenesis, suggesting that distinct mechanisms of action are used by 11-oxygenated androgens and T. These mechanisms, however, seem to merge on the same target(s) to impair Leydig cell androgen production. Such a negative feedback mechanism may be of relevance in the context of the decline in androgen secretion per milligram testis tissue that accompanies the first wave of spermatogenesis in pubertal African catfish.
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  • 15
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    Cell & tissue research 295 (1999), S. 151-158 
    ISSN: 1432-0878
    Keywords: Key words Class II MHC-positive cells ; Human leukocyte antigen-DR ; Dental pulp ; Dendritic cells ; Macrophages ; Ultrastructure ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The distribution and ultrastructure of class II major histocompatibility complex (MHC)-positive cells were investigated in human dental pulp, employing immunohistochemistry using an anti-human leukocyte antigen (HLA)-DR-monoclonal antibody. HLA-DR-immunopositive cells, appearing spindle-like or dendritic in profile, were densely distributed throughout the dental pulp. Under the electron microscope, these cells exhibited various sizes of vesicles containing clear or opaque contents, multivesicular bodies and characteristic fine tubulovesicular structures in their cytoplasm. Some reactive cells possessed coated pits and vesicles including electron-dense materials, indicating an active endocytosis. At the periphery of the pulp tissue, the HLA-DR-immunopositive cells were predominantly situated in the subodontoblastic layer, with some located in the odontoblast layer and/or predentin and extending their cytoplasmic processes into the dentinal tubules. Cell processes of these cells occasionally made contact with several odontoblast processes in the same way as the nerve fibers in the predentin. These cells never contained the typical phagosomes frequently observed in the HLA-DR-immunoreactive macrophages in the subodontoblastic layer and the pulp core. The results suggest that the HLA-DR-immunopositive cells in the odontoblast layer and/or predentin have some regulatory function on the odontoblasts under physiological conditions, in addition to their involvement in the initial defense reaction after tooth injury.
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  • 16
    ISSN: 1432-0878
    Keywords: Key words Neuromelanin ; Neuron ; Peroxidase ; Oxygen metabolism ; High-definition light microscopy ; Electron microscopy ; Ultrastructure ; Cytochemistry ; Substantia nigra ; Lumbricusterrestris (Annelida)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Histochemical examination of 1-μm tissue sections from the dorsal nerve plexus of the earthworm, Lumbricus terrestris, reveals multiple brown intraneuronal granules. These granules contain material morphologically and histochemically consistent with neuromelanin. When viewed with transmission electron microscopy, these were seen as single membrane-enclosed biphasic granules with diameters of 370–730 nm. Exposure of L. terrestris to high-level environmental oxygen resulted in an increase in the number of neuromelanin-like pigment granules within the neurons of the circular muscle layer. As measured by ortho-phenylenediamine hydrochloride, the endogenous peroxidase activity of extracts from worms incubated in high-level environmental oxygen was 51% more than controls. The endogenous peroxidase activity was localized in situ with 3,3-diaminobenzidine (DAB) and was found to increase in and around the neuromelanin-like pigment-containing neurons within the circular muscle layer. These studies suggest that the nerve net of L. terrestris may serve as a model to study the role of neuromelanin production in oxidative stress and its relationship to endogenous peroxidases.
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  • 17
    ISSN: 1432-0878
    Keywords: Key words Melanin-concentrating hormone neurons ; Lateral hypothalamic slice culture ; Immunocytochemistry ; Ultrastructure ; In situ hybridization ; Competitive RT-PCR ; Leptin assay ; Rat (Sprague Dawley)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Hypothalamic slices containing the lateral hypothalamic area (LHA) were prepared from 6- to 8-day-old rats and maintained in stationary culture for up to 35 days in order to analyse how well the melanin-concentrating hormone (MCH) neurons survived. As previously reported for other brain areas, this method yielded a long-term well-preserved organotypic organization. Light- and electron-microscopic investigations showed that differentiation continued and that synaptic contacts developed in vitro. After a period of elimination of damaged cells and fibres, most of the remaining neurons and glial cells retained a normal morphology throughout the culture period. MCH neurons, in particular, survived well as attested by the strong immunocytochemical and in situ hybridization signals still observed after several weeks. In a comparison with the day of explantation, competitive reverse transcription/polymerase chain reaction demonstrated the remarkable stability of the level of MCH mRNA at least until the 20th day in culture; after 30 days, the clear decrease in this level seemed to be correlated with a loss of MCH neurons, rather than with a decrease in MCH expression. After 10 days of culture, the incubation of slices in the presence of the hormone leptin (50 ng/ml) resulted in a strong decrease of MCH gene expression, suggesting that MCH neurons retained their physiological properties. Thus, the LHA slice stationary culture, especially between one and three weeks (i.e. after tissue stabilization and before extensive cell loss), appears to be a suitable method for physiological and pharmacological studies of these neurons.
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  • 18
    ISSN: 1432-0878
    Keywords: Key words ECL cells ; Gastrin ; Reserpine ; Organelles ; Ultrastructure ; Rat (Sprague-Dawley)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The histamine-storing ECL cells in the stomach play a key role in the control of acid secretion. They contain granules, secretory vesicles and microvesicles, and sustained gastrin stimulation results in the additional formation of vacuoles and lipofuscin bodies. The cells are rich in the vesicle monoamine transporter type-2 (VMAT-2), which can be inhibited by reserpine. The present study examines the effect of reserpine on ECL-cell ultrastructure and histamine compartmentalization. Rats received reserpine and/or gastrin. Reserpine was given twice by the intraperitoneal route (25 mg/kg once daily). Gastrin-17 was given by subcutaneous infusion (5 nmol/kg/h), starting at the time of the first reserpine injection and continuing for 4 days when the rats were killed. At this stage, histamine in the oxyntic mucosa was unaffected by reserpine but elevated by gastrin. Immunocytochemical analysis (confocal microscopy) showed ECL-cell histamine in control and gastrin-treated rats to be localized in cytoplasmic organelles (e.g., secretory vesicles). After treatment with reserpine alone or reserpine+gastrin, ECL-cell histamine occurred mainly in the cytosol. Planimetric analysis (electron microscopy) of ECL cells showed reserpine to increase the number, size and volume density of the granules and to reduce the size and volume density of the secretory vesicles. Gastrin reduced the number and volume density of granules and secretory vesicles, increased the number and volume density of microvesicles and caused vacuoles and lipofuscin bodies to appear. Reserpine+gastrin increased the number, volume density and size of the granules. Reserpine prevented the effects of gastrin on secretory vesicles, vacuoles and microvesicles, but did not prevent the development of lipofuscin. Our findings are in line with the views: (1) that preformed cytosolic histamine is taken up by granules/secretory vesicles via VMAT-2, that histamine is instrumental in the transformation of granules into secretory vesicles and in their consequent enlargement and (2) that vacuoles are formed by the fusion of large secretory vesicles.
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  • 19
    ISSN: 1615-6102
    Keywords: Cumulus oophorus ; Ovarian follicle ; Fertilization ; Ultrastructure ; Immunocytochemistry ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The fine structure of the human cumulus oophorus has been reviewed on the basis of scanning and transmission electron microscopic observations as well as of immunofluorescence data. Tissues sampled from preovulatory ovarian follicles and cumulus-enclosed oocytes and fertilized eggs (collected from the oviduct or obtained during in vitro fertilization procedures) have been evaluated from a microtopographic and morphodynamic point of view in order to better clarify the possible role of this population of cells. In particular, the following aspects have been studied and discussed: the presence of multiple close contacts (modulated by the interposition of the zona pellucida) between the oocyte surface and the long microvillous evaginations projecting from the inner aspect of corona cells surface (through these structures the intraovarian cumulus oophorus may control oocyte growth and metabolism up until the time of ovulation); the occurrence of different subpopulations of cells (steroid-synthetic cells, cells producing adhesive proteins, leukocytes, macrophages) in the postovulatory, extraovarian cumulus oophorus surrounding oocytes, zygotes and early developing embryos. All these elements found in the cumulus mass may positively act, through their paracrine activities, on the chemical composition of the microenvironment in which fertilization occurs.
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  • 20
    ISSN: 1615-6102
    Keywords: Plasmalemmic cord ; Pollen grain ; Ultrastructure ; Magnolia ×soulangeana
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary InMagnolia ×soulangeana pollen grains the generative cell (GC) does not become totally free within the vegetative cell (VC), at least until the pollen tube emergence. Due to a deviation in its detachment process from the sporoderm, the opposing ends of the VC plasmalemma do not fuse themselves when the GC moves away from the intine. Consequently, the interplasmalemmic space surrounding the GC does not become isolated but rather maintains continuity with the sporoderm through a complex formation that we have called plasmalemmic cord. The real existence of this formation was confirmed through serial sectioning showing the plasmalemmic cord to consist of the VC plasmalemma. In its initial portion it is occupied by a reasonably accentuated wall ingrowth of the inner layer of the intine (intine 3). In the remainder portion, neither of the cytochemical tests used in this work have revealed the presence of a significant amount of wall material. However, ultrathin sections of samples processed either chemically or by cryofixation showed the existence of an intricate system of tubules and vesicles, some of which are evaginations of the VC plasmalemma. The hypothesis that the plasmalemmic cord may have a role in the complex interactions between the two pollen cells is discussed.
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  • 21
    ISSN: 1615-6102
    Keywords: Anatomy ; Floral nectary ; Modified stomata ; Phloem ; Pisum sativum ; Stereology ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The floral nectary ofPisum sativum L. is situated on the receptacle at the base of the gynoecium. The gland receives phloem alone which departed the vascular bundles supplying the staminal column. Throughout the nectary, only the companion cells of the phloem exhibited wall ingrowths typical of transfer cells. Modified stomata on the nectary surface served as exits for nectar, but stomatal pores developed well before the commencement of secretion. Furthermore, stomatal pores on the nectary usually closed by occlusion, not by guard-cell movements. Pore occlusion was detected most frequently in post-secretory and secretory glands, and less commonly in pre-secretory nectaries. A quantitative stereological study revealed few changes in nectary fine structure between buds, flowers secreting nectar, and post-secretory flowers. Dissolution of abundant starch grains in plastids of subepidermal secretory cells when secretion commenced suggests that starch is a precursor of nectar carbohydrate production. Throughout nectary development, mitochondria were consistently the most plentiful organelle in both epidermal and subepidermal cells, and in addition to the relative paucity of dictyosomes, endoplasmic reticulum, and their associated vesicles, the evidence suggests that floral nectar secretion inP. sativum is an energy-requiring (eccrine) process, rather that granulocrine.
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  • 22
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    Artificial life and robotics 3 (1999), S. 242-245 
    ISSN: 1614-7456
    Keywords: Mutation ; Self-reproduction ; Evolvability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract A self-reproduction process is described and discussed via a network model of machines and description tapes. The emergence of a core network which dynamically sustains the rewriting processes of machines on tapes is reported. The structures of the core networks are generic, and include Eigen's hypercycle as a special case. In the cell assembly model, where each cell contains machines and tapes, we show that the instability of the core network in some cells is sustained by those cells with stable core networks. The instability of the core network is transfered to its offspring when the cells divide. What is inherited here is not the patterns of tapes, but the way machines read tapes in a core network.
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  • 23
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    Molecular genetics and genomics 261 (1999), S. 463-471 
    ISSN: 1617-4623
    Keywords: Key words Granule-bound starch synthase ; Starch ; Waxy ; Wheat ; Mutation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract To date, few mutations in wheat have been characterized at the molecular level. In this study, the mutations in the three waxy alleles in waxy wheat (Wx-A1b,Wx-B1b and Wx-D1b) were characterized, and waxy gene expression was compared in several wheat lines, including hexaploid and tetraploid waxy lines of wheat. Southern analysis showed that the Wx-B1b allele had sustained a deletion which included the entire coding region of the Wx-B1 gene. DNA homologous to waxy gene sequences was still present in the Wx-A1b and Wx-D1b alleles of the hexaploid waxy mutant. Transcripts of waxy alleles were also detected in both hexaploid and tetraploid mutants at 10 days post-anthesis, but the transcript level was dramatically reduced compared to that found in non-waxy lines. Isolation of cDNAs showed that transcripts were produced by both the Wx-A1b and Wx-D1b alleles. A 23-bp deletion sustained by the Wx-A1b allele at an exon-intron junction results in the use of a cryptic splice site during mRNA processing. The deduced translation product encoded by the Wx-A1b cDNA lacks 39 amino acids, including the putative ADP-glucose binding site and a portion of the transit peptide. The C-terminal region of the deduced protein encoded by the Wx-D1b cDNA lacks the last 30 amino acids. Comparison of the genomic sequences of the null and wild-type Wx-D1 alleles indicated that 588 bp were deleted in the Wx-D1b mutation, and that the last 261 bp of the Wx-D1b cDNA originated from the normally non-transcribed 3′ flanking region. Like several deletion mutations characterized in other plant species, both Wx-A1b and Wx-D1b alleles contain small DNA insertions, or filler DNA, between the deletion end-points.
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  • 24
    ISSN: 1615-6102
    Keywords: Endosymbiont ; Mycetocyte ; Mycetome ; Oocyte ; Transovarial transmission ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary All anoplurans live symbiotically with prokaryotic microorganisms hosted in specialized cells, termed mycetocytes. In nymphs and males mycetocytes are distributed between midgut epithelial cells. In females, besides the midgut, mycetocytes are found in the reproductive organs where they are located at the base of ovarioles in contact with lateral oviducts. The mycetocyte-associated symbionts are transmitted from one generation to the next transovarially. Here, the results of histological and ultrastructural studies on the distribution and transmission of symbiotic microorganisms within the ovaries of the anopluranHaematopinus suis are presented. Interestingly, during advanced oogenesis (i.e., choriogenesis) of this species all symbionts are localized extracellularly and form a tight mass located at the posterior pole of the oocyte just below the hydropyle. In insects studied so far, such localization of transovarially transmitted microorganisms has been reported only in the closely related speciesHaematopinus eurysternus.
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  • 25
    ISSN: 1432-136X
    Keywords: Key words Freeze tolerance ; Sciatic nerve ; Cryoinjury ; Dehydration ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We investigated function and ultrastructure of sciatic nerves isolated from wood frogs (Rana sylvatica) endemic to the Northwest Territories, Canada, following freezing at −2.5 °C, −5.0 °C, or −7.5 °C. All frogs frozen at −2.5 °C, and most frogs (71%) frozen at −5.0 °C, recovered within 14 h after thawing began; however, frogs did not survive exposure to −7.5 °C. Sciatic nerves isolated from frogs frozen at −7.5 °C were refractory to electrical stimulation, whereas those obtained from frogs surviving exposure to −2.5 °C or −5.0 °C generally exhibited normal characteristics of compound action potentials. Frogs responded to freezing by mobilizing hepatic glycogen reserves to synthesize the cryoprotectant glucose, which increased 20-fold in the liver and 40-fold in the blood. Ultrastructural analyses of nerves harvested from frogs in each treatment group revealed that freezing at −2.5 °C or −5.0 °C had little or no effect on tissue and cellular organization, but that (lethal) exposure to −7.5 °C resulted in marked shrinkage of the axon, degeneration of mitochondria within the axoplasm, and extensive delamination of myelin sheaths of the surrounding Schwann cells.
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  • 26
    ISSN: 1435-232X
    Keywords: Key words Familial gastric cancer ; E-cadherin ; Germline ; Mutation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Gastric cancer is the most common cancer in Korea. Germline mutations of the E-cadherin gene have recently been identified in familial gastric cancer patients. We screened five Korean familial gastric cancer patients to investigate germline mutations of the E-cadherin gene. These patients fulfilled the following criteria: presence of at least two gastric cancer patients within first-degree relatives and one patient diagnosed before the age of 50 years. Abnormal band patterns were found in exons 6 and 10 in two familial gastric cancer patients by polymerase chain reaction-single strand conformation polymorphism analysis (probands from the SNU-G2 and SNU-G1001 families, respectively). DNA sequencing analysis of the E-cadherin gene of these two patients revealed missense mutations in each exon. The SNU-G2 proband harbored a missense mutation from aspartic acid (GAT) to glycine (GGT) at codon 244 in exon 6 of the E-cadherin gene, and the SNU-G1001 proband had a missense mutation from valine (GTG) to alanine (GCG) at codon 487 in exon 10. The SNU-G2 proband was diagnosed with gastric cancer at the age of 38; three brothers and two sisters had died of gastric cancer under the age of 50, and their mother had died of gastric cancer at the age of 63. The SNU-G1001 proband was diagnosed with gastric cancer at the age of 42 and one brother had died of gastric cancer at the age of 49. In summary, we found germline mutations of the E-cadherin gene in two of five Korean familial gastric cancer patients screened.
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  • 27
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    Journal of human genetics 44 (1999), S. 377-382 
    ISSN: 1435-232X
    Keywords: Key words Galactosemia ; Galactokinase (GALK) ; Mutation ; Genotype ; Phenotype
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Galactokinase (GALK) deficiency is an autosomal recessive disorder, which causes cataract formation in children not maintained on a lactose-free diet. We characterized the human GALK gene by screening a Japanese genomic DNA phage library, and found that several nucleotides in the 5′-untranslated region and introns 1, 2, and 5 in our GALK genomic analysis differed from published data. A 20-bp tandem repeat was found in three places in intron 5, which were considered insertion sequences. We identified five novel mutations in seven unrelated Japanese patients with GALK deficiency. There were three missense mutations and two deletions. All three missense mutations (R256W, T344M, and G349S) occurred at CpG dinucleotides, and the T344M and G349S mutations occurred in the conserved region. The three missense mutations led to a drastic reduction in GALK activity when individual mutant cDNAs were expressed in a mammalian cell system. These findings indicated that these missense mutations caused GALK deficiency. The two deletions, of 410delG and 509–510delGT, occurred at the nucleotide repeats GGGGGG and GTGTGT, respectively, and resulted in in-frame nonsense codons at amino acids 163 and 201. These mutations arose by slipped strand mispairing. All five mutations occurred at hot spots in the CpG dinucleotide for missense mutations and in short direct repeats for deletions. These five mutations in Japanese have not yet been identified in Caucasians. We speculate that the origin of GALK mutations in Japanese is different from that in Caucasians.
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  • 28
    ISSN: 1435-232X
    Keywords: Key words 6-Pyruvoyl-tetrahydropterin synthase (PTPS) deficiency ; Tetrahydrobiopterin ; Mutation ; Missense ; Splicing ; Phenotype and genotype
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We identified three mutations in four Japanese patients with central type 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency. One missense mutation was a C-to-T transition, resulting in the substitution of Pro by Ser at codon 87 (P87S) in exon 5. Another missense mutation was a G-to-A transition, resulting in the substitution of Asp by Asn at codon 96 (D96N) in exon 5. A splicing mutation was found by skipping of exon 4 on PTPS mRNA analysis, and a G-to-A transition at the third base of codon 81 (E81E) and at the terminal base in exon 4 were detected on genomic PTPS DNA analysis. The E81E mutation affected the splice donor site of exon 4 and caused the splicing error. In COS cell expression analysis, the P87S and D96N mutant constructs revealed, respectively, 52% and 10% of wild-type activity. Patients with P87S/P87S (52%/52% in-vitro PTPS activity) exhibited 0.11 and 0 μU/g hemoglobin [Hb] in erythrocyte PTPS activity (wild-type control: 11-29 μU/gHb) erythrocyte PTPS activity, and the patient with P87S/D96N mutations (52%/10%) had 0.97 μU/gHb in PTPS erythrocyte activity. The PTPS erythrocyte activity did not coincide with the in-vitro PTPS activity based on patient genotype.
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  • 29
    ISSN: 1435-232X
    Keywords: Key words Tuberous sclerosis complex ; TSC1 gene ; TSC2 gene ; Hamartin ; Tuberin ; Mutation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We have surveyed the mutations of TSC1 and TSC2 from 38 (25 sporadic, 11 familial, and 2 unknown) Japanese patients with tuberous sclerosis complex. In 23 of 38 subjects, we detected 18 new mutations in addition to 4 mutations that had been previously reported. We also found 3 new polymorphisms. The mutations were not clustered on a particular exon in either of the genes. Seven TSC1 mutations found in 3 familial and 4 sporadic cases were on the exons (3 missense, 2 nonsense point mutations, a 1-base insertion, and a 2-bp deletion). Fifteen TSC2 mutations were found in 5 familial cases, 10 sporadic cases, and 1 unknown case. The 12 mutations were on the exons (8 missense, 1 nonsense point mutations, a 1-bp insertion, a 5-bp deletion, and a 4-bp replacement) and 3 point mutations were on the exon–intron junctions. Although the patients with TSC2 mutations tend to exhibit relatively severe mental retardation in comparison to those with TSC1 mutations, a genotype–phenotype correlation could not yet be established. The widespread distribution of TSC1/TSC2 mutations hinders the development of a simple diagnostic test, and the identification of individual mutations does not provide the prediction of prognosis.
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  • 30
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    Parasitology research 85 (1999), S. 999-1006 
    ISSN: 1432-1955
    Keywords: Key wordsEchinococcus granulosus ; Praziquantel ; Metacestode ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The efficacy of praziquantel against the metacestode of Echinococcus granulosus was studied by means of in vitro incubations or in vivo experiments. The results of in vitro incubations indicated that the effectiveness of praziquantel was higher when the parasite material comprised cysts from cyst masses than in the case of intact cysts that retained their adventitial layer. Ultrastructural alterations in the germinal layer of collapsed cysts incubated in vitro were detected. The results obtained in mice after 4 months of treatment demonstrated no significant difference between the control and treated groups with regard to the number and wet weight of developed cysts. However, ultrastructural alterations were detected in the cyst tissue that were similar to those described in the in vitro experiment. In contrast, the effect of chemoprophylaxis on the number and the wet weight of developed cysts was extremely significant as compared with the control value, the efficacy being 99.41% and 98.32%, respectively. Moreover, ultrastructural observations of the cyst tissue revealed loss of its integrity, and no intact cyton was observed in the germinal layer of the developed cyst.
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  • 31
    ISSN: 1432-1955
    Keywords: Key words Monogenea ; Capsalidae ; Benedenia rohdei ; B. lutjani ; Ectoparasites ; Lutjanus carponotatus ; Glands ; Ultrastructure ; Adhesion ; Attachment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The anterior adhesive areas of Benedenia rohdei from the gills and B. lutjani from the pelvic fins of Lutjanuscarponotatus at Heron Island, Australia, were studied using scanning and transmission electron microscopy. All specimens were fixed when detached from host tissue. Both monogenean species have two disc-like anteroventral attachment organs, each of which has an anterolateral adhesive area divided into three adjacent zones by tegument from the ventral surface of the attachment organ. A rod-shaped secretion and a smaller, roughly spherical secretion are associated with the anterior adhesive areas in both species; a third type of secretion occurs anteriorly but outside these adhesive areas. The electron-dense spherical secretory bodies released onto the anterior adhesive zones in these Benedenia spp. are of a single type and differ ultrastructurally from those previously reported in monogeneans living on teleost hosts. A correlation, therefore, between secretion morphology and host type is not supported. No relationship was found between parasite microhabitat and secretion morphology.
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  • 32
    ISSN: 1435-232X
    Keywords: Key words Methylmalonic acidemia ; Methylmalonyl-CoA mutase ; Adenosylcobalamin ; Organic aciduria ; Mutation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Genetic defects in the methylmalonyl-CoA mutase (MCM) gene cause methylmalonic acidemia (MMA). Only three mutations have been reported among Oriental patients to date. We studied fibroblast cell lines established from three Japanese patients with MCM deficiency. Enzymatic study showed that these patients had the mut 0 type of MMA. Nucleotide sequencing of MCM cDNAs identified three missense mutations: a T to A change at nucleotide position 2082, which results in an amino acid substitution of Glu669 for valine (V669E); a T to A change at position 1179 with the corresponding amino acid substitution of Asp368 for valine (V368D); and a G to A change at position 1182 with the corresponding amino acid substitution of His369 for arginine (R369H). Each of the three missense mutations abolished MCM activity according to a transient expression study. Alignment of these mutations with a recently reported homology model of human MCM allowed us to speculate on the effect of these nonconservative amino acid substitutions on MCM activity: V368D and R369H affected residues in the β/α-(TIM-) barrel domain, on one of the two α-helices that form the dimer interface, while V669E altered a residue in the adenosylcobalamin-binding domain in the C terminus.
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  • 33
    ISSN: 1435-232X
    Keywords: Key words Branchio-oto-renal (BOR) syndrome ; EYA1 ; Mutation ; Japanese ; Hearing impairment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Advances in molecular genetics have recently revealed that mutations in the EYA1 gene are responsible for branchio-oto-renal (BOR) syndrome in European and other populations. This is the first report confirming that an EYA1 gene mutation is also disease-causing in an Asian population. We have described one Japanese BOR syndrome family showing a novel mutation in exon 7 of the EYA1 gene. There was extensive variation of clinical phenotypes within this family. When the physician is confronted with a BOR family showing a wide variation in clinical expression, molecular genetic testing helps to achieve accurate diagnosis.
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  • 34
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    Journal of human genetics 44 (1999), S. 272-273 
    ISSN: 1435-232X
    Keywords: Key words Complement ; C7 ; Mutation ; Polymorphism ; Population genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract A new single-nucleotide polymorphism has been found in the 3′ untranslated region of the complement component C7 gene. It is present with similar frequencies in the Japanese and Germans. This polymorphism would be a useful marker in the genetic study of C6 and C7 deficiencies.
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  • 35
    ISSN: 1435-232X
    Keywords: Key words Fanconi anemia ; FAA gene ; Mutation ; Polymorphism ; SSCP ; Direct sequencing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Fanconi anemia (FA) is an autosomal recessive disorder characterized by pancytopenia, predisposition to cancers, and a diverse variety of congenital malformations. At least eight complementation groups, A through H, have been described. Recently, the FA-A gene (FAA) has been isolated, and a large number of distinct mutations reported in ethnically diverse FA-A patients. Here, we report on the mutation analysis of five FA patients by single-strand conformation polymorphism. Out of five patients, at least three were found to have mutations in the FAA gene. The first patient was a compound heterozygote with a 1-bp deletion and a single-base substitution. The second patient had a heterozygous 2-bp deletion, which introduces a premature termination codon, and the third patient had a heterozygous splice donor site mutation in intron 27.
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  • 36
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-01-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goldman, L R -- New York, N.Y. -- Science. 1998 Dec 4;282(5395):1825-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9874633" target="_blank"〉PubMed〈/a〉
    Keywords: Child ; Environmental Exposure ; Environmental Pollutants/adverse effects ; Government Agencies ; Humans ; Lead/adverse effects ; Lead Poisoning/*prevention & control ; United States ; United States Environmental Protection Agency
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 37
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    Publication Date: 1999-01-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spear, P G -- New York, N.Y. -- Science. 1998 Dec 11;282(5396):1999-2000.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Northwestern University Medical School, Department of Microbiology-Immunology, Chicago, IL 60611, USA. p-spear@nwu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9874652" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Adhesion ; Cytoskeletal Proteins/genetics/*metabolism ; Dystroglycans ; Humans ; Laminin/metabolism ; Lassa Fever/*virology ; Lassa virus/*metabolism ; Leprosy/*microbiology ; Lymphocytic choriomeningitis virus/metabolism ; Membrane Glycoproteins/genetics/*metabolism ; Models, Biological ; Mycobacterium leprae/*metabolism ; Receptors, Virus/metabolism ; Schwann Cells/microbiology
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 38
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    Publication Date: 1999-01-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gough, M -- New York, N.Y. -- Science. 1998 Dec 4;282(5395):1823.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9874631" target="_blank"〉PubMed〈/a〉
    Keywords: 2,4,5-Trichlorophenoxyacetic Acid/adverse effects ; 2,4-Dichlorophenoxyacetic Acid/adverse effects ; Confidentiality/*legislation & jurisprudence ; Defoliants, Chemical ; Financing, Government ; Humans ; *Public Policy ; Research/*legislation & jurisprudence ; *Research Support as Topic ; Tetrachlorodibenzodioxin/adverse effects ; United States
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 39
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    Publication Date: 1999-01-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Adams, M W -- Stiefel, E I -- New York, N.Y. -- Science. 1998 Dec 4;282(5395):1842-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA. adams@bmb.uga.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9874636" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Carbon Monoxide/chemistry ; Clostridium/*enzymology ; Crystallography, X-Ray ; Cyanides/chemistry ; Humans ; Hydrogen/*metabolism ; Hydrogenase/*chemistry/*metabolism ; Iron/chemistry ; Ligands ; Oxidation-Reduction ; Pyruvic Acid/metabolism
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-01-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, E -- New York, N.Y. -- Science. 1998 Dec 11;282(5396):1972-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9874643" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/cytology/*genetics/physiology ; Cell Lineage ; Chromosome Mapping ; DNA, Helminth/chemistry/genetics ; Evolution, Molecular ; Gene Expression Regulation ; *Genes, Helminth ; Genetic Techniques ; *Genome ; Humans ; Mutation ; *Sequence Analysis, DNA
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 41
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-09-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hagmann, M -- New York, N.Y. -- Science. 1999 Aug 20;285(5431):1200-1, 1203.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10484727" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Acetyltransferases/chemistry/metabolism ; Animals ; Cell Cycle Proteins/chemistry/metabolism ; Chromatin/chemistry/*metabolism/*ultrastructure ; *Gene Expression Regulation ; Histone Acetyltransferases ; Histones/*metabolism ; Methylation ; *Mitosis ; Phosphorylation ; Protein Structure, Secondary ; Protein-Arginine N-Methyltransferases/metabolism ; Transcription Factors ; p300-CBP Transcription Factors
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-09-08
    Description: Postdoctoral appointments can have different functions and meanings, depending on the field and whether the postdoc is a man or a woman. The Ph.D.'s-Ten Years Later study confirmed that in biochemistry, the postdoc, not the Ph.D., has become the general proving ground for excellence both in academia and industry. Because they spent a longer time in these "mandatory" postdocs, biochemists had the largest proportion of untenured faculty 10 to 13 years after the Ph. D. In mathematics, where substantially fewer postdoctoral positions are available, Ph.D.'s taking postdocs are more likely to obtain faculty positions, but this is true only for men. University administrators should be accountable for monitoring the total time spent in these positions and should provide administrative assistance for skills training, career growth, and the job search. In addition, creative solutions concerning the dual-career couple phenomenon are necessary.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nerad, M -- Cerny, J -- New York, N.Y. -- Science. 1999 Sep 3;285(5433):1533-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate Division, University of California, Berkeley, 424 Sproul Hall, Berkeley, CA 94720-5900, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10477510" target="_blank"〉PubMed〈/a〉
    Keywords: *Biochemistry/education ; *Career Mobility ; *Education, Graduate ; Employment ; Faculty ; *Fellowships and Scholarships ; Female ; Humans ; Male ; *Mathematics ; Salaries and Fringe Benefits ; Societies, Scientific ; Time Factors ; United States ; Universities
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-01-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin, J -- New York, N.Y. -- Science. 1998 Dec 18;282(5397):2175-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9890822" target="_blank"〉PubMed〈/a〉
    Keywords: Budgets ; Cartilage ; *Complementary Therapies/economics/organization & administration ; Controlled Clinical Trials as Topic ; Humans ; Lung Neoplasms/therapy ; National Institutes of Health (U.S.)/economics/*organization & administration ; Research Support as Topic ; Tissue Extracts/therapeutic use ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-09-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wickelgren, I -- New York, N.Y. -- Science. 1999 Aug 13;285(5430):999.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10475850" target="_blank"〉PubMed〈/a〉
    Keywords: Biotechnology/history ; Genetics, Medical/history ; Genome, Human ; History, 20th Century ; Humans ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-12-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Collignon, P -- New York, N.Y. -- Science. 1999 Dec 3;286(5446):1855-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10610574" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Viral/analysis ; *Gammaretrovirus/immunology ; Humans ; Retroviridae Infections/diagnosis/*transmission ; *Swine/virology ; *Transplantation, Heterologous/adverse effects
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-05-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Service, R F -- New York, N.Y. -- Science. 1999 Apr 23;284(5414):578-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10328734" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Electric Stimulation ; Electrodes ; Electrodes, Implanted ; *Electronics ; Electrophysiology ; Humans ; Nerve Net/*physiology ; Nervous System Diseases/*therapy ; Neurons/*physiology ; Rats ; Silicon ; *Transistors, Electronic
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-12-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Langan, P -- Schoenborn, B P -- New York, N.Y. -- Science. 1999 Nov 5;286(5442):1089.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10610521" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography/*instrumentation ; *Neutrons ; Proteins/*chemistry ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-11-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nilsson, A -- Rose, J -- New York, N.Y. -- Science. 1999 Oct 29;286(5441):894.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10577238" target="_blank"〉PubMed〈/a〉
    Keywords: *Biological Specimen Banks/legislation & jurisprudence ; Biotechnology ; Ethics Committees ; *Ethics, Research ; *Genetic Privacy ; *Genetic Research ; Government Regulation ; Humans ; *Privacy/legislation & jurisprudence ; Public Policy ; Sweden
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-07-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Laver, W G -- New York, N.Y. -- Science. 1999 Jun 25;284(5423):2089.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10409063" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallization ; Neuraminidase/*chemistry ; *Space Flight ; *Spacecraft ; United States ; United States National Aeronautics and Space Administration ; *Weightlessness
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    Publication Date: 1999-09-25
    Description: The flow of information from calcium-mobilizing receptors to nuclear factor of activated T cells (NFAT)-dependent genes is critically dependent on interaction between the phosphatase calcineurin and the transcription factor NFAT. A high-affinity calcineurin-binding peptide was selected from combinatorial peptide libraries based on the calcineurin docking motif of NFAT. This peptide potently inhibited NFAT activation and NFAT-dependent expression of endogenous cytokine genes in T cells, without affecting the expression of other cytokines that require calcineurin but not NFAT. Substitution of the optimized peptide sequence into the natural calcineurin docking site increased the calcineurin responsiveness of NFAT. Compounds that interfere selectively with the calcineurin-NFAT interaction without affecting calcineurin phosphatase activity may be useful as therapeutic agents that are less toxic than current drugs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aramburu, J -- Yaffe, M B -- Lopez-Rodriguez, C -- Cantley, L C -- Hogan, P G -- Rao, A -- R01 AI 40127/AI/NIAID NIH HHS/ -- R01 GM056203/GM/NIGMS NIH HHS/ -- R01 HL 03601/HL/NHLBI NIH HHS/ -- R43 AI 43726/AI/NIAID NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1999 Sep 24;285(5436):2129-33.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10497131" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Calcineurin/*metabolism ; Calcineurin Inhibitors ; Cell Nucleus/metabolism ; Cyclosporine/pharmacology ; Cytokines/biosynthesis/genetics ; DNA-Binding Proteins/*antagonists & inhibitors/chemistry/metabolism ; Gene Expression Regulation ; Genes, Reporter ; HeLa Cells ; Humans ; Immunosuppressive Agents/chemistry/metabolism/*pharmacology ; Jurkat Cells ; Molecular Sequence Data ; NFATC Transcription Factors ; *Nuclear Proteins ; Oligopeptides/chemistry/metabolism/*pharmacology ; Peptide Library ; Peptides/chemistry/metabolism/*pharmacology ; Phosphorylation ; Recombinant Fusion Proteins/metabolism ; T-Lymphocytes/*drug effects/immunology ; Transcription Factors/*antagonists & inhibitors/chemistry/metabolism ; Transfection
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-01-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lawler, C -- Erbisch, F -- New York, N.Y. -- Science. 1999 Jan 1;283(5398):33-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9917260" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biotechnology ; Mice ; Mice, Transgenic ; *Patents as Topic ; Plants, Genetically Modified/*genetics ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-10-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shapiro, H T -- New York, N.Y. -- Science. 1999 Sep 24;285(5436):2065.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10523197" target="_blank"〉PubMed〈/a〉
    Keywords: Advisory Committees ; *Bioethical Issues ; Embryo Research ; Embryo, Mammalian/*cytology ; Ethics Committees ; Financing, Government ; Government Regulation ; Humans ; Private Sector ; *Public Policy ; Research/*standards ; Research Support as Topic ; *Stem Cells ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-06-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Colvin, M -- New York, N.Y. -- Science. 1999 May 28;284(5419):1480.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Duke Comprehensive Cancer Center, Durham, NC 27710, USA. colvi003@mc.duke.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10383327" target="_blank"〉PubMed〈/a〉
    Keywords: Chemistry, Pharmaceutical/history ; Drug Design ; History, 20th Century ; Nobel Prize ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-05-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Landick, R -- New York, N.Y. -- Science. 1999 Apr 23;284(5414):598-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706, USA. landick@macc.wisc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10328742" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pairing ; Binding Sites ; DNA/chemistry/*metabolism ; DNA-Directed RNA Polymerases/genetics/*metabolism ; Escherichia coli/enzymology/genetics ; Gene Expression Regulation ; Humans ; Models, Genetic ; Mutation ; Nucleic Acid Conformation ; Oligodeoxyribonucleotides, Antisense/chemistry/metabolism ; RNA, Messenger/chemistry/*metabolism ; *Terminator Regions, Genetic ; *Transcription, Genetic ; Viral Proteins/metabolism
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-07-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hagmann, M -- New York, N.Y. -- Science. 1999 Jul 2;285(5424):21-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10428690" target="_blank"〉PubMed〈/a〉
    Keywords: *Genetic Techniques ; *Genome, Human ; Humans ; *Mutation ; *Polymorphism, Genetic
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-04-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Service, R F -- New York, N.Y. -- Science. 1999 Apr 2;284(5411):33-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10215526" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Arrhythmias, Cardiac/physiopathology ; Calcium/metabolism ; Calcium-Binding Proteins/metabolism ; Cardiac Output, Low/*physiopathology ; Chronic Disease ; *Computer Simulation ; Heart/*physiopathology ; Humans ; *Models, Cardiovascular ; *Myocardial Contraction ; Potassium/metabolism ; Potassium Channels/metabolism
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-05-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hagmann, M -- New York, N.Y. -- Science. 1999 Apr 30;284(5415):723, 725.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10336390" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Breast Neoplasms/*genetics/pathology ; *Disease Models, Animal ; Female ; *Genes, BRCA1 ; Genes, p53 ; Humans ; Mammary Glands, Animal/pathology ; Mammary Neoplasms, Animal/*genetics/pathology ; Mice ; Mice, Knockout ; Mice, Transgenic ; Mutation
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-04-30
    Description: Notch signaling defines an evolutionarily ancient cell interaction mechanism, which plays a fundamental role in metazoan development. Signals exchanged between neighboring cells through the Notch receptor can amplify and consolidate molecular differences, which eventually dictate cell fates. Thus, Notch signals control how cells respond to intrinsic or extrinsic developmental cues that are necessary to unfold specific developmental programs. Notch activity affects the implementation of differentiation, proliferation, and apoptotic programs, providing a general developmental tool to influence organ formation and morphogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Artavanis-Tsakonas, S -- Rand, M D -- Lake, R J -- NS26084/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1999 Apr 30;284(5415):770-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts General Hospital Cancer Center, Department of Cell Biology, Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10221902" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Cell Communication ; Cell Division ; Cell Nucleus/metabolism ; Humans ; Intracellular Signaling Peptides and Proteins ; Ligands ; Membrane Proteins/*physiology ; Receptors, Cell Surface/*physiology ; Receptors, Notch ; *Signal Transduction ; Transcription, Genetic
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    Publication Date: 1999-04-24
    Description: The lack of an adequate hominid fossil record in eastern Africa between 2 and 3 million years ago (Ma) has hampered investigations of early hominid phylogeny. Discovery of 2.5 Ma hominid cranial and dental remains from the Hata beds of Ethiopia's Middle Awash allows recognition of a new species of Australopithecus. This species is descended from Australopithecus afarensis and is a candidate ancestor for early Homo. Contemporary postcranial remains feature a derived humanlike humeral/femoral ratio and an apelike upper arm-to-lower arm ratio.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Asfaw, B -- White, T -- Lovejoy, O -- Latimer, B -- Simpson, S -- Suwa, G -- New York, N.Y. -- Science. 1999 Apr 23;284(5414):629-35.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rift Valley Research Service, Post Office Box 5717, Addis Ababa, Ethiopia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10213683" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; Bones of Upper Extremity/anatomy & histology ; Dentition ; Ethiopia ; *Fossils ; History, Ancient ; Hominidae/anatomy & histology/*classification ; Humans ; Leg Bones/anatomy & histology ; Paleodontology ; Phylogeny ; Skull/anatomy & histology ; Terminology as Topic ; Tooth/anatomy & histology
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    Publication Date: 1999-11-05
    Description: The Brca1 (breast cancer gene 1) tumor suppressor protein is phosphorylated in response to DNA damage. Results from this study indicate that the checkpoint protein kinase ATM (mutated in ataxia telangiectasia) was required for phosphorylation of Brca1 in response to ionizing radiation. ATM resides in a complex with Brca1 and phosphorylated Brca1 in vivo and in vitro in a region that contains clusters of serine-glutamine residues. Phosphorylation of this domain appears to be functionally important because a mutated Brca1 protein lacking two phosphorylation sites failed to rescue the radiation hypersensitivity of a Brca1-deficient cell line. Thus, phosphorylation of Brca1 by the checkpoint kinase ATM may be critical for proper responses to DNA double-strand breaks and may provide a molecular explanation for the role of ATM in breast cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cortez, D -- Wang, Y -- Qin, J -- Elledge, S J -- GM44664/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Nov 5;286(5442):1162-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Verna and Mars McLean Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10550055" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Ataxia Telangiectasia/genetics ; Ataxia Telangiectasia Mutated Proteins ; BRCA1 Protein/*metabolism ; Breast Neoplasms/genetics ; Cell Cycle Proteins ; Cell Line ; *DNA Damage ; *DNA Repair ; DNA, Complementary ; DNA-Binding Proteins ; Female ; Gamma Rays ; Genes, BRCA1 ; Genetic Predisposition to Disease ; HeLa Cells ; Heterozygote ; Humans ; Molecular Sequence Data ; Mutation ; Phosphorylation ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Tumor Suppressor Proteins
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-02-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haraldsdottir, R -- New York, N.Y. -- Science. 1999 Jan 22;283(5401):487.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9988648" target="_blank"〉PubMed〈/a〉
    Keywords: Bioethics ; Databases, Factual/*legislation & jurisprudence ; Genetic Privacy ; *Genetic Research ; Humans ; Iceland ; Medical Records Systems, Computerized/*legislation & jurisprudence ; Patient Advocacy
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-05-21
    Description: Ran, a small guanosine triphosphatase, is suggested to have additional functions beyond its well-characterized role in nuclear trafficking. Guanosine triphosphate-bound Ran, but not guanosine diphosphate-bound Ran, stimulated polymerization of astral microtubules from centrosomes assembled on Xenopus sperm. Moreover, a Ran allele with a mutation in the effector domain (RanL43E) induced the formation of microtubule asters and spindle assembly, in the absence of sperm nuclei, in a gammaTuRC (gamma-tubulin ring complex)- and XMAP215 (Xenopus microtubule associated protein)-dependent manner. Therefore, Ran could be a key signaling molecule regulating microtubule polymerization during mitosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilde, A -- Zheng, Y -- GM56312-01/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 May 21;284(5418):1359-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Carnegie Institution of Washington, Department of Embryology, Baltimore, MD 21210, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10334991" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Extracts ; Cell Nucleus/metabolism ; Centrosome/physiology ; Dimethyl Sulfoxide/pharmacology ; Dyneins/physiology ; GTP Phosphohydrolases/genetics/*metabolism ; Guanosine Diphosphate/metabolism ; Guanosine Triphosphate/*metabolism ; Male ; Microtubule-Associated Proteins/metabolism ; Microtubules/*metabolism/ultrastructure ; Mutation ; Nuclear Proteins/analysis/genetics/*metabolism/pharmacology ; Ovum ; Recombinant Fusion Proteins/metabolism/pharmacology ; Sperm Head/physiology ; Spindle Apparatus/chemistry/*metabolism/ultrastructure ; Tubulin/analysis/metabolism ; Xenopus ; *Xenopus Proteins ; ran GTP-Binding Protein
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-12-03
    Description: Polypeptides emerging from the ribosome must fold into stable three-dimensional structures and maintain that structure throughout their functional lifetimes. Maintaining quality control over protein structure and function depends on molecular chaperones and proteases, both of which can recognize hydrophobic regions exposed on unfolded polypeptides. Molecular chaperones promote proper protein folding and prevent aggregation, and energy-dependent proteases eliminate irreversibly damaged proteins. The kinetics of partitioning between chaperones and proteases determines whether a protein will be destroyed before it folds properly. When both quality control options fail, damaged proteins accumulate as aggregates, a process associated with amyloid diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wickner, S -- Maurizi, M R -- Gottesman, S -- New York, N.Y. -- Science. 1999 Dec 3;286(5446):1888-93.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892-4255, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10583944" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/metabolism ; Amyloid/metabolism ; Animals ; Endopeptidases/*metabolism ; Eukaryotic Cells/metabolism ; Humans ; Models, Biological ; Molecular Chaperones/*metabolism ; Prions/metabolism ; Prokaryotic Cells/metabolism ; Protein Biosynthesis ; *Protein Folding ; Proteins/*chemistry/*metabolism ; Ubiquitins/metabolism
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  • 64
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-01-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wickelgren, I -- New York, N.Y. -- Science. 1999 Jan 1;283(5398):14-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9917254" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/metabolism ; Cells, Cultured ; Dimerization ; Drug Design ; Humans ; Neurons/*metabolism ; Potassium Channels/metabolism ; Rats ; Receptors, GABA-B/*chemistry/*metabolism ; Signal Transduction ; gamma-Aminobutyric Acid/metabolism
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  • 65
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-10-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shastri, L -- New York, N.Y. -- Science. 1999 Sep 10;285(5434):1673-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10523181" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; Infant ; *Learning ; *Mathematics ; *Neural Networks (Computer)
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  • 66
    Publication Date: 1999-12-22
    Description: The SGS1 gene of the yeast Saccharomyces cerevisiae encodes a DNA helicase with homology to the human Bloom's syndrome gene BLM and the Werner's syndrome gene WRN. The SRS2 gene of yeast also encodes a DNA helicase. Simultaneous deletion of SGS1 and SRS2 is lethal in yeast. Here, using a conditional mutation of SGS1, it is shown that DNA replication and RNA polymerase I transcription are drastically inhibited in the srs2Delta sgs1-ts strain at the restrictive temperature. Thus, SGS1 and SRS2 function in DNA replication and RNA polymerase I transcription. These functions may contribute to the various defects observed in Werner's and Bloom's syndromes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, S K -- Johnson, R E -- Yu, S L -- Prakash, L -- Prakash, S -- CA80882/CA/NCI NIH HHS/ -- GM19261/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Dec 17;286(5448):2339-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sealy Center for Molecular Science, University of Texas Medical Branch at Galveston, 6.104 Medical Research Building, 11th and Mechanic Streets, Galveston, TX 77555-1061, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10600744" target="_blank"〉PubMed〈/a〉
    Keywords: Bloom Syndrome/genetics ; Codon ; DNA Helicases/genetics/*physiology ; *DNA Replication ; DNA, Fungal/biosynthesis ; Fungal Proteins/genetics/*physiology ; Gene Deletion ; Genes, Fungal ; Humans ; Mutation ; RNA Polymerase I/metabolism ; RNA Polymerase II/metabolism ; RNA Polymerase III/metabolism ; RNA, Fungal/biosynthesis ; RNA, Messenger/biosynthesis/genetics ; RNA, Ribosomal/biosynthesis ; RNA, Transfer, Amino Acid-Specific/biosynthesis ; RecQ Helicases ; Saccharomyces cerevisiae/*genetics/metabolism ; *Saccharomyces cerevisiae Proteins ; *Transcription, Genetic ; Werner Syndrome/genetics
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  • 67
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-10-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Normile, D -- Pennisi, E -- New York, N.Y. -- Science. 1999 Sep 24;285(5436):2038-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10523188" target="_blank"〉PubMed〈/a〉
    Keywords: Chromosome Mapping ; Chromosomes, Human, Pair 22/*genetics ; Contig Mapping ; *Human Genome Project ; Humans ; International Cooperation ; *Sequence Analysis, DNA
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  • 68
    Publication Date: 1999-10-03
    Description: Precursors of alpha-defensin peptides require activation for bactericidal activity. In mouse small intestine, matrilysin colocalized with alpha-defensins (cryptdins) in Paneth cell granules, and in vitro it cleaved the pro segment from cryptdin precursors. Matrilysin-deficient (MAT-/-) mice lacked mature cryptdins and accumulated precursor molecules. Intestinal peptide preparations from MAT-/- mice had decreased antimicrobial activity. Orally administered bacteria survived in greater numbers and were more virulent in MAT-/- mice than in MAT+/+ mice. Thus, matrilysin functions in intestinal mucosal defense by regulating the activity of defensins, which may be a common role for this metalloproteinase in its numerous epithelial sites of expression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, C L -- Ouellette, A J -- Satchell, D P -- Ayabe, T -- Lopez-Boado, Y S -- Stratman, J L -- Hultgren, S J -- Matrisian, L M -- Parks, W C -- New York, N.Y. -- Science. 1999 Oct 1;286(5437):113-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics, Division of Allergy and Pulmonary Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. wilson_c@kids.wustl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10506557" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Catalysis ; Cytoplasmic Granules/enzymology ; Escherichia coli/growth & development ; Escherichia coli Infections/immunology/microbiology ; Female ; Humans ; *Immunity, Innate ; *Immunity, Mucosal ; Intestinal Mucosa/enzymology/immunology/microbiology ; Intestine, Small/enzymology/*immunology/microbiology ; Male ; Matrix Metalloproteinase 7 ; Metalloendopeptidases/genetics/*metabolism ; Mice ; Molecular Sequence Data ; Paneth Cells/enzymology ; Protein Precursors/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Salmonella typhimurium/growth & development/pathogenicity ; Tissue Extracts/pharmacology
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  • 69
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-06-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Av-Gay, Y -- New York, N.Y. -- Science. 1999 Jun 4;284(5420):1621.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10383337" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteria/*genetics/pathogenicity ; *Biotechnology ; *Containment of Biohazards ; Ecosystem ; *Genetic Engineering ; Guidelines as Topic ; Humans ; United States ; Viruses/*genetics/pathogenicity
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  • 70
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-05-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Culotta, E -- New York, N.Y. -- Science. 1999 Apr 23;284(5414):572-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10328732" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Ethiopia ; Facial Bones/anatomy & histology ; *Fossils ; History, Ancient ; *Hominidae/anatomy & histology/classification ; Humans ; Paleodontology ; Skull/anatomy & histology ; Tooth/anatomy & histology
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  • 71
    Publication Date: 1999-10-16
    Description: Dense genetic maps of human, mouse, and rat genomes that are based on coding genes and on microsatellite and single-nucleotide polymorphism markers have been complemented by precise gene homolog alignment with moderate-resolution maps of livestock, companion animals, and additional mammal species. Comparative genetic assessment expands the utility of these maps in gene discovery, in functional genomics, and in tracking the evolutionary forces that sculpted the genome organization of modern mammalian species.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Brien, S J -- Menotti-Raymond, M -- Murphy, W J -- Nash, W G -- Wienberg, J -- Stanyon, R -- Copeland, N G -- Jenkins, N A -- Womack, J E -- Marshall Graves, J A -- New York, N.Y. -- Science. 1999 Oct 15;286(5439):458-62, 479-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Genomic Diversity, National Cancer Institute, Frederick, MD 21702-1201, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10521336" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Domestic/genetics ; Base Sequence ; *Chromosome Mapping ; *Evolution, Molecular ; Genetic Markers ; *Genome ; *Genome, Human ; Humans ; Mammals/*genetics ; Mutation ; *Phylogeny ; Rodentia/genetics
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  • 72
    Publication Date: 1999-06-12
    Description: To monitor changes in alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor distribution in living neurons, the AMPA receptor subunit GluR1 was tagged with green fluorescent protein (GFP). This protein (GluR1-GFP) was functional and was transiently expressed in hippocampal CA1 neurons. In dendrites visualized with two-photon laser scanning microscopy or electron microscopy, most of the GluR1-GFP was intracellular, mimicking endogenous GluR1 distribution. Tetanic synaptic stimulation induced a rapid delivery of tagged receptors into dendritic spines as well as clusters in dendrites. These postsynaptic trafficking events required synaptic N-methyl-D-aspartate (NMDA) receptor activation and may contribute to the enhanced AMPA receptor-mediatedtransmission observed during long-term potentiation and activity-dependent synaptic maturation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shi, S H -- Hayashi, Y -- Petralia, R S -- Zaman, S H -- Wenthold, R J -- Svoboda, K -- Malinow, R -- New York, N.Y. -- Science. 1999 Jun 11;284(5421):1811-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10364548" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Dendrites/*metabolism/ultrastructure ; Electric Stimulation ; Hippocampus/cytology/physiology ; Humans ; Long-Term Potentiation ; *Neuronal Plasticity ; Neurons/*physiology ; Organ Culture Techniques ; Rats ; Receptor Aggregation ; Receptors, AMPA/*metabolism ; Receptors, N-Methyl-D-Aspartate/*physiology ; Recombinant Fusion Proteins/metabolism ; Synapses/metabolism/*physiology ; Synaptic Transmission ; Tetany
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  • 73
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-02-05
    Description: Traditionally, the interest of population and evolutionary biologists in infectious diseases has been almost exclusively in their role as agents of natural selection in higher organisms. Recently, this interest has expanded to include the genetic structure and evolution of microparasite populations, the mechanisms of pathogenesis and the immune response, and the population biology, ecology, and evolutionary consequences of medical and public health interventions. This article describes recent work in these areas, emphasizing the ways in which quantitative, population-biological approaches have been contributing to the understanding of infectious disease and the design and evaluation of interventions for their treatment and prevention.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Levin, B R -- Lipsitch, M -- Bonhoeffer, S -- New York, N.Y. -- Science. 1999 Feb 5;283(5403):806-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Emory University, 1510 Clifton Road, Atlanta, GA 30322, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9933155" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Physiological Phenomena ; *Biological Evolution ; Drug Resistance, Microbial ; Humans ; Infection/immunology/*microbiology ; Molecular Epidemiology ; Parasites/genetics/physiology ; Parasitic Diseases/immunology/*parasitology ; Population Dynamics ; Vaccination ; Virus Physiological Phenomena
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  • 74
    Publication Date: 1999-08-28
    Description: Class II transactivator (CIITA) is a global transcriptional coactivator of human leukocyte antigen-D (HLA-D) genes. CIITA contains motifs similar to guanosine triphosphate (GTP)-binding proteins. This report shows that CIITA binds GTP, and mutations in these motifs decrease its GTP-binding and transactivation activity. Substitution of these motifs with analogous sequences from Ras restores CIITA function. CIITA exhibits little GTPase activity, yet mutations in CIITA that confer GTPase activity reduce transcriptional activity. GTP binding by CIITA correlates with nuclear import. Thus, unlike other GTP-binding proteins, CIITA is involved in transcriptional activation that uses GTP binding to facilitate its own nuclear import.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Harton, J A -- Cressman, D E -- Chin, K C -- Der, C J -- Ting, J P -- AI29564/AI/NIAID NIH HHS/ -- AI41751/AI/NIAID NIH HHS/ -- AI45580/AI/NIAID NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1999 Aug 27;285(5432):1402-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lineberger Comprehensive Cancer Center, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10464099" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Animals ; Binding Sites ; COS Cells ; Cell Line ; Cell Nucleus/*metabolism ; GTP-Binding Proteins/chemistry/genetics/*metabolism ; *Genes, MHC Class II ; Guanosine Triphosphate/*metabolism ; HLA-DR Antigens/genetics ; Humans ; Mutation ; *Nuclear Proteins ; Promoter Regions, Genetic ; Temperature ; Trans-Activators/chemistry/genetics/*metabolism ; Transcription Factors/metabolism ; *Transcriptional Activation
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  • 75
    Publication Date: 1999-09-25
    Description: Mass mortalities due to disease outbreaks have recently affected major taxa in the oceans. For closely monitored groups like corals and marine mammals, reports of the frequency of epidemics and the number of new diseases have increased recently. A dramatic global increase in the severity of coral bleaching in 1997-98 is coincident with high El Nino temperatures. Such climate-mediated, physiological stresses may compromise host resistance and increase frequency of opportunistic diseases. Where documented, new diseases typically have emerged through host or range shifts of known pathogens. Both climate and human activities may have also accelerated global transport of species, bringing together pathogens and previously unexposed host populations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Harvell, C D -- Kim, K -- Burkholder, J M -- Colwell, R R -- Epstein, P R -- Grimes, D J -- Hofmann, E E -- Lipp, E K -- Osterhaus, A D -- Overstreet, R M -- Porter, J W -- Smith, G W -- Vasta, G R -- 1PO1 ES09563/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 1999 Sep 3;285(5433):1505-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ecology and Evolutionary Biology, Cornell University, Ithaca, NY 14853, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10498537" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aquaculture ; *Climate ; Cnidaria ; *Disease Outbreaks/*veterinary ; Humans ; Infection/epidemiology/*etiology/transmission/*veterinary ; *Marine Biology ; Oceans and Seas ; Water Pollution
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  • 76
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-12-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Curry, M -- Hazard-Daniel, A -- Daniel, H J -- New York, N.Y. -- Science. 1999 Dec 3;286(5446):1854-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10610573" target="_blank"〉PubMed〈/a〉
    Keywords: *Dietary Supplements/adverse effects ; Drug Prescriptions ; Drug-Related Side Effects and Adverse Reactions ; *Legislation, Drug ; *Legislation, Food ; United States ; United States Food and Drug Administration
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  • 77
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-08-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wojcik, J F -- New York, N.Y. -- Science. 1999 Jul 30;285(5428):663.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10454918" target="_blank"〉PubMed〈/a〉
    Keywords: *Biological Evolution ; Humans ; *Religion and Science
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  • 78
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-01-08
    Description: Humans show considerable interindividual variation in susceptibility to weight gain in response to overeating. The physiological basis of this variation was investigated by measuring changes in energy storage and expenditure in 16 nonobese volunteers who were fed 1000 kilocalories per day in excess of weight-maintenance requirements for 8 weeks. Two-thirds of the increases in total daily energy expenditure was due to increased nonexercise activity thermogenesis (NEAT), which is associated with fidgeting, maintenance of posture, and other physical activities of daily life. Changes in NEAT accounted for the 10-fold differences in fat storage that occurred and directly predicted resistance to fat gain with overfeeding (correlation coefficient = 0.77, probability 〈 0.001). These results suggest that as humans overeat, activation of NEAT dissipates excess energy to preserve leanness and that failure to activate NEAT may result in ready fat gain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Levine, J A -- Eberhardt, N L -- Jensen, M D -- DK45343/DK/NIDDK NIH HHS/ -- DK50456/DK/NIDDK NIH HHS/ -- M01 RR00535/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1999 Jan 8;283(5399):212-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Endocrine Research Unit, Mayo Clinic and Mayo Foundation, 200 First Street Southwest, Rochester, MN 55905, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9880251" target="_blank"〉PubMed〈/a〉
    Keywords: Activities of Daily Living ; *Adipose Tissue ; Adult ; Basal Metabolism ; Body Composition ; Calorimetry, Indirect ; *Energy Intake ; *Energy Metabolism ; Exercise ; Female ; Humans ; Hyperphagia/*physiopathology ; Male ; *Movement ; Posture ; *Weight Gain
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  • 79
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-10-16
    Description: Epigenetics is the study of heritable changes in gene expression that occur without a change in DNA sequence. Epigenetic phenomena have major economic and medical relevance, and several, such as imprinting and paramutation, violate Mendelian principles. Recent discoveries link the recognition of nucleic acid sequence homology to the targeting of DNA methylation, chromosome remodeling, and RNA turnover. Although epigenetic mechanisms help to protect cells from parasitic elements, this defense can complicate the genetic manipulation of plants and animals. Essential for normal development, epigenetic controls become misdirected in cancer cells and other human disease syndromes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wolffe, A P -- Matzke, M A -- New York, N.Y. -- Science. 1999 Oct 15;286(5439):481-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Embryology, National Institute of Child Heath and Human Development, NIH, Building 18T, Room 106, Bethesda, MD 20892-5431, USA. awlme@helix.nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10521337" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; DNA Methylation ; Evolution, Molecular ; *Gene Expression Regulation ; Gene Expression Regulation, Developmental ; *Gene Silencing ; Genetic Diseases, Inborn/genetics ; Genome ; Humans ; Neoplasms/genetics ; RNA/genetics/metabolism ; Repetitive Sequences, Nucleic Acid
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  • 80
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-06-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉L'Heureux, N -- Germain, L -- Auger, F A -- New York, N.Y. -- Science. 1999 Jun 4;284(5420):1621-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10383338" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biomedical Engineering ; *Blood Vessels/physiology/transplantation ; *Culture Techniques ; Dogs ; Endothelium, Vascular ; Graft Survival ; Humans ; Transplantation, Heterologous
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  • 81
    Publication Date: 1999-11-05
    Description: Glutamatergic neurotransmission is controlled by presynaptic metabotropic glutamate receptors (mGluRs). A subdomain in the intracellular carboxyl-terminal tail of group III mGluRs binds calmodulin and heterotrimeric guanosine triphosphate-binding protein (G protein) betagamma subunits in a mutually exclusive manner. Mutations interfering with calmodulin binding and calmodulin antagonists inhibit G protein-mediated modulation of ionic currents by mGluR 7. Calmodulin antagonists also prevent inhibition of excitatory neurotransmission via presynaptic mGluRs. These results reveal a novel mechanism of presynaptic modulation in which Ca(2+)-calmodulin is required to release G protein betagamma subunits from the C-tail of group III mGluRs in order to mediate glutamatergic autoinhibition.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Connor, V -- El Far, O -- Bofill-Cardona, E -- Nanoff, C -- Freissmuth, M -- Karschin, A -- Airas, J M -- Betz, H -- Boehm, S -- New York, N.Y. -- Science. 1999 Nov 5;286(5442):1180-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurochemistry, Max Planck Institute for Brain Research, Deutschordenstrasse 46, 60528 Frankfurt, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10550060" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Calcium/metabolism ; Calmodulin/antagonists & inhibitors/*metabolism ; Cells, Cultured ; Dimerization ; G Protein-Coupled Inwardly-Rectifying Potassium Channels ; GTP-Binding Proteins/*metabolism ; Glutamic Acid/*metabolism ; Hippocampus/cytology/metabolism ; Humans ; Mice ; Molecular Sequence Data ; Neurons/metabolism ; Potassium Channels/metabolism ; *Potassium Channels, Inwardly Rectifying ; Presynaptic Terminals/metabolism ; Propionates/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Metabotropic Glutamate/antagonists & inhibitors/*metabolism ; Recombinant Fusion Proteins/metabolism ; Sesterterpenes ; Signal Transduction ; Swine ; *Synaptic Transmission ; Terpenes/pharmacology
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  • 82
    Publication Date: 1999-06-26
    Description: Regulation of circadian period in humans was thought to differ from that of other species, with the period of the activity rhythm reported to range from 13 to 65 hours (median 25.2 hours) and the period of the body temperature rhythm reported to average 25 hours in adulthood, and to shorten with age. However, those observations were based on studies of humans exposed to light levels sufficient to confound circadian period estimation. Precise estimation of the periods of the endogenous circadian rhythms of melatonin, core body temperature, and cortisol in healthy young and older individuals living in carefully controlled lighting conditions has now revealed that the intrinsic period of the human circadian pacemaker averages 24.18 hours in both age groups, with a tight distribution consistent with other species. These findings have important implications for understanding the pathophysiology of disrupted sleep in older people.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Czeisler, C A -- Duffy, J F -- Shanahan, T L -- Brown, E N -- Mitchell, J F -- Rimmer, D W -- Ronda, J M -- Silva, E J -- Allan, J S -- Emens, J S -- Dijk, D J -- Kronauer, R E -- MO1-RR02635/RR/NCRR NIH HHS/ -- P01-AG09975/AG/NIA NIH HHS/ -- R01-GM53559/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Jun 25;284(5423):2177-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Circadian, Neuroendocrine, and Sleep Disorders Section, Division of Endocrinology, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10381883" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aged ; Aging/*physiology ; Biological Clocks/genetics/*physiology ; Body Temperature ; Circadian Rhythm/genetics/*physiology ; Darkness ; Female ; Humans ; Hydrocortisone/blood ; Light ; Male ; Melatonin/blood ; Middle Aged ; Sleep
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  • 83
    Publication Date: 1999-02-26
    Description: Chlamydia infections are epidemiologically linked to human heart disease. A peptide from the murine heart muscle-specific alpha myosin heavy chain that has sequence homology to the 60-kilodalton cysteine-rich outer membrane proteins of Chlamydia pneumoniae, C. psittaci, and C. trachomatis was shown to induce autoimmune inflammatory heart disease in mice. Injection of the homologous Chlamydia peptides into mice also induced perivascular inflammation, fibrotic changes, and blood vessel occlusion in the heart, as well as triggering T and B cell reactivity to the homologous endogenous heart muscle-specific peptide. Chlamydia DNA functioned as an adjuvant in the triggering of peptide-induced inflammatory heart disease. Infection with C. trachomatis led to the production of autoantibodies to heart muscle-specific epitopes. Thus, Chlamydia-mediated heart disease is induced by antigenic mimicry of a heart muscle-specific protein.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bachmaier, K -- Neu, N -- de la Maza, L M -- Pal, S -- Hessel, A -- Penninger, J M -- New York, N.Y. -- Science. 1999 Feb 26;283(5406):1335-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Amgen Institute, Ontario Cancer Institute, Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, Ontario M5G 2C1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10037605" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Amino Acid Sequence ; Animals ; Antigens, Bacterial/chemistry/immunology ; Autoantibodies/biosynthesis ; Autoimmune Diseases/immunology/*microbiology/pathology ; B-Lymphocytes/immunology ; Bacterial Outer Membrane Proteins/chemistry/*immunology ; CD4-Positive T-Lymphocytes/immunology ; Chlamydia/*immunology ; Chlamydia Infections/complications/*immunology ; Chlamydia trachomatis/immunology ; CpG Islands ; Humans ; Immunization ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; *Molecular Mimicry ; Molecular Sequence Data ; Myocarditis/immunology/*microbiology/pathology ; Myocardium/immunology/pathology ; Myosin Heavy Chains/chemistry/*immunology ; Oligodeoxyribonucleotides/immunology ; Sequence Homology, Amino Acid
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  • 84
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-07-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wolpoff, M H -- New York, N.Y. -- Science. 1999 Jun 11;284(5421):1774-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10391795" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; Hominidae/*classification/genetics ; Humans ; Phylogeny
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  • 85
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-10-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bagla, P -- New York, N.Y. -- Science. 1999 Oct 1;286(5437):25, 27.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10532885" target="_blank"〉PubMed〈/a〉
    Keywords: *Academies and Institutes/economics ; *Brain ; Humans ; India ; International Cooperation ; *Research
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 86
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-07-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wong, V -- Goodenough, D A -- New York, N.Y. -- Science. 1999 Jul 2;285(5424):62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10428705" target="_blank"〉PubMed〈/a〉
    Keywords: Calcium Channels/metabolism ; Cell Membrane/metabolism/ultrastructure ; Claudins ; Cloning, Molecular ; Humans ; Ion Channels ; Ion Transport ; Kidney Diseases/genetics/*metabolism ; Kidney Tubules/*metabolism/ultrastructure ; Lipid Bilayers/metabolism ; Magnesium/blood/*metabolism ; Magnesium Deficiency/genetics/*metabolism ; Membrane Proteins/genetics/*physiology ; Mutation ; Tight Junctions/*metabolism
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  • 87
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-04-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dan, Z -- Lei, X -- New York, N.Y. -- Science. 1999 Mar 26;283(5410):1990-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10206897" target="_blank"〉PubMed〈/a〉
    Keywords: Academies and Institutes/*legislation & jurisprudence ; Aged ; Aged, 80 and over ; Aging/genetics ; *Blood Specimen Collection ; China ; Databases, Nucleic Acid ; Disclosure ; *Genetic Research ; Health Surveys ; Humans ; Informed Consent ; International Cooperation ; Internationality ; Life Style ; *Longevity/genetics ; Mass Media/*legislation & jurisprudence ; Research Support as Topic
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  • 88
    Publication Date: 1999-04-09
    Description: Imprinted genes display parent-of-origin-dependent monoallelic expression that apparently regulates complex mammalian traits, including growth and behavior. The Peg3 gene is expressed in embryos and the adult brain from the paternal allele only. A mutation in the Peg3 gene resulted in growth retardation, as well as a striking impairment of maternal behavior that frequently resulted in death of the offspring. This result may be partly due to defective neuronal connectivity, as well as reduced oxytocin neurons in the hypothalamus, because mutant mothers were deficient in milk ejection. This study provides further insights on the evolution of epigenetic regulation of imprinted gene dosage in modulating mammalian growth and behavior.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, L -- Keverne, E B -- Aparicio, S A -- Ishino, F -- Barton, S C -- Surani, M A -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 1999 Apr 9;284(5412):330-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome CRC Institute of Cancer and Developmental Biology, and Physiological Laboratory, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10195900" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Newborn ; Brain/metabolism ; Crosses, Genetic ; Female ; Gene Expression ; Gene Targeting ; *Genomic Imprinting ; *Growth ; Hypothalamus/cytology/metabolism ; Kruppel-Like Transcription Factors ; Lactation ; Male ; *Maternal Behavior ; Mice ; Mutation ; Neural Pathways ; Neurons/metabolism ; Oxytocin/metabolism ; Phenotype ; *Protein Kinases ; Proteins/genetics/*physiology ; *Transcription Factors ; *Weight Gain
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  • 89
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-04-02
    Description: A general problem in biology is how to incorporate information about evolutionary history and adaptation into taxonomy. The problem is exemplified in attempts to define our own genus, Homo. Here conventional criteria for allocating fossil species to Homo are reviewed and are found to be either inappropriate or inoperable. We present a revised definition, based on verifiable criteria, for Homo and conclude that two species, Homo habilis and Homo rudolfensis, do not belong in the genus. The earliest taxon to satisfy the criteria is Homo ergaster, or early African Homo erectus, which currently appears in the fossil record at about 1.9 million years ago.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wood, B -- Collard, M -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 1999 Apr 2;284(5411):65-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anthropology, George Washington University, 2110 G Street NW, Washington, DC 20052, USA. bwood@gwu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10102822" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Animals ; Biological Evolution ; Body Constitution ; Brain/anatomy & histology ; *Fossils ; Hominidae/anatomy & histology/*classification ; Humans ; Jaw/anatomy & histology ; Locomotion ; Phylogeny ; Terminology as Topic
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  • 90
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-04-24
    Description: Retroviral DNA integration is catalyzed by the viral protein integrase. Here, it is shown that DNA-dependent protein kinase (DNA-PK), a host cell protein, also participates in the reaction. DNA-PK-deficient murine scid cells infected with three different retroviruses showed a substantial reduction in retroviral DNA integration and died by apoptosis. Scid cell killing was not observed after infection with an integrase-defective virus, suggesting that abortive integration is the trigger for death in these DNA repair-deficient cells. These results suggest that the initial events in retroviral integration are detected as DNA damage by the host cell and that completion of the integration process requires the DNA-PK-mediated repair pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Daniel, R -- Katz, R A -- Skalka, A M -- AI40721/AI/NIAID NIH HHS/ -- AI40835/AI/NIAID NIH HHS/ -- CA71515/CA/NCI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1999 Apr 23;284(5414):644-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10213687" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; CHO Cells ; Cell Survival ; Cells, Cultured ; Cricetinae ; DNA Damage ; *DNA Repair ; DNA, Viral/*genetics/metabolism ; DNA-Activated Protein Kinase ; *DNA-Binding Proteins ; Genetic Vectors ; HIV-1/genetics ; Integrases/genetics/metabolism ; Mice ; Mutation ; Protein-Serine-Threonine Kinases/*metabolism ; Retroviridae/*genetics/physiology ; *Virus Integration ; Virus Replication
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  • 91
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-02-05
    Description: Costimulation of both the CD3 and CD28 receptors is essential for T cell activation. Induction of adenosine 3',5'-monophosphate (cAMP)-specific phosphodiesterase-7 (PDE7) was found to be a consequence of such costimulation. Increased PDE7 in T cells correlated with decreased cAMP, increased interleukin-2 expression, and increased proliferation. Selectively reducing PDE7 expression with a PDE7 antisense oligonucleotide inhibited T cell proliferation; inhibition was reversed by blocking the cAMP signaling pathways that operate through cAMP-dependent protein kinase (PKA). Thus, PDE7 induction and consequent suppression of PKA activity is required for T cell activation, and inhibition of PDE7 could be an approach to treating T cell-dependent disorders.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, L -- Yee, C -- Beavo, J A -- DK21723/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1999 Feb 5;283(5403):848-51.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology and Molecular and Cellular Biology Program, Box 357280, University of Washington School of Medicine, Seattle, WA 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9933169" target="_blank"〉PubMed〈/a〉
    Keywords: 3',5'-Cyclic-AMP Phosphodiesterases/*biosynthesis/genetics/metabolism ; Antibodies ; Antigens, CD28/immunology/*physiology ; Antigens, CD3/immunology/*physiology ; CD4-Positive T-Lymphocytes/enzymology/immunology ; Cells, Cultured ; Cyclic AMP/metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Cyclic Nucleotide Phosphodiesterases, Type 7 ; Enzyme Induction ; Humans ; Interleukin-2/biosynthesis ; Isoenzymes/*biosynthesis/genetics/metabolism ; *Lymphocyte Activation ; Oligonucleotides, Antisense/pharmacology ; RNA, Messenger/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; T-Lymphocytes/*enzymology/*immunology/metabolism ; Tumor Cells, Cultured
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  • 92
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-11-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Daniel, T M -- New York, N.Y. -- Science. 1999 Oct 8;286(5438):239.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10577189" target="_blank"〉PubMed〈/a〉
    Keywords: Bronchiectasis/history ; Depressive Disorder/*history/pathology ; *Famous Persons ; Fingers/*pathology ; History, 19th Century ; Humans ; Literature, Modern/*history ; Male ; Medicine in Art ; Paintings ; Tuberculosis/*history/pathology
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  • 93
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-10-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hawkins, M M -- Barratt, C L -- New York, N.Y. -- Science. 1999 Oct 1;286(5437):51-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10532889" target="_blank"〉PubMed〈/a〉
    Keywords: Child ; Congenital Abnormalities/etiology ; Developmental Disabilities/etiology ; Female ; Fertilization in Vitro/*adverse effects ; Great Britain ; Humans ; Male ; Neoplasms/etiology ; Pregnancy ; Pregnancy Outcome ; Registries ; Risk Factors
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  • 94
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-04-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bagla, P -- New York, N.Y. -- Science. 1999 Mar 12;283(5408):1614-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10189310" target="_blank"〉PubMed〈/a〉
    Keywords: Academies and Institutes ; *Economics, Pharmaceutical ; *Ethnic Groups ; Humans ; India ; Medicine, Ayurvedic ; Plant Extracts/*economics ; *Plants, Medicinal
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  • 95
    Publication Date: 1999-07-31
    Description: Many immune receptors are composed of separate ligand-binding and signal-transducing subunits. In natural killer (NK) and T cells, DAP10 was identified as a cell surface adaptor protein in an activating receptor complex with NKG2D, a receptor for the stress-inducible and tumor-associated major histocompatibility complex molecule MICA. Within the DAP10 cytoplasmic domain, an Src homology 2 (SH2) domain-binding site was capable of recruiting the p85 subunit of the phosphatidylinositol 3-kinase (PI 3-kinase), providing for NKG2D-dependent signal transduction. Thus, NKG2D-DAP10 receptor complexes may activate NK and T cell responses against MICA-bearing tumors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, J -- Song, Y -- Bakker, A B -- Bauer, S -- Spies, T -- Lanier, L L -- Phillips, J H -- AI30581/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1999 Jul 30;285(5428):730-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉DNAX Research Institute, 901 California Avenue, Palo Alto, CA 94304, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10426994" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Cell Line ; Cytotoxicity, Immunologic ; Humans ; Killer Cells, Natural/*immunology/metabolism ; Ligands ; *Lymphocyte Activation ; Membrane Proteins/chemistry/genetics/*metabolism ; Mice ; Molecular Sequence Data ; NK Cell Lectin-Like Receptor Subfamily K ; Neoplasms/immunology ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation ; Phosphotyrosine/metabolism ; Receptors, Immunologic/chemistry/genetics/*metabolism ; Receptors, Natural Killer Cell ; Signal Transduction ; T-Lymphocytes/*immunology/metabolism ; Tumor Cells, Cultured ; src Homology Domains
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  • 96
    Publication Date: 1999-04-09
    Description: Phosphorylation of inhibitor of kappa B (IkappaB) proteins is an important step in the activation of the transcription nuclear factor kappa B (NF-kappaB) and requires two IkappaB kinases, IKK1 (IKKalpha) and IKK2 (IKKbeta). Mice that are devoid of the IKK2 gene had extensive liver damage from apoptosis and died as embryos, but these mice could be rescued by the inactivation of the gene encoding tumor necrosis factor receptor 1. Mouse embryonic fibroblast cells that were isolated from IKK2-/- embryos showed a marked reduction in tumor necrosis factor-alpha (TNF-alpha)- and interleukin-1alpha-induced NF-kappaB activity and an enhanced apoptosis in response to TNF-alpha. IKK1 associated with NF-kappaB essential modulator (IKKgamma/IKKAP1), another component of the IKK complex. These results show that IKK2 is essential for mouse development and cannot be substituted with IKK1.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Q -- Van Antwerp, D -- Mercurio, F -- Lee, K F -- Verma, I M -- New York, N.Y. -- Science. 1999 Apr 9;284(5412):321-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Salk Institute, La Jolla, CA 92037, USA. Signal Pharmaceuticals, San Diego, CA 92121, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10195897" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Cell Line ; DNA-Binding Proteins/metabolism ; Embryonic and Fetal Development ; Gene Targeting ; I-kappa B Kinase ; I-kappa B Proteins ; Interleukin-1/pharmacology ; Liver/cytology/*embryology ; Mice ; NF-kappa B/metabolism ; Phosphorylation ; Polymerase Chain Reaction ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Receptors, Tumor Necrosis Factor/genetics/metabolism ; Recombinant Fusion Proteins/metabolism ; Sequence Deletion ; Signal Transduction ; Transcription Factor RelA ; Transcription Factors/metabolism ; Tumor Necrosis Factor-alpha/pharmacology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 97
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-01-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bagla, P -- New York, N.Y. -- Science. 1999 Jan 15;283(5400):309.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9925483" target="_blank"〉PubMed〈/a〉
    Keywords: Bioethics ; *Biotechnology/economics/legislation & jurisprudence ; *Genetics, Medical/economics/legislation & jurisprudence ; *Genome ; Genome, Human ; Genome, Plant ; Humans ; India ; *Molecular Biology/economics/legislation & jurisprudence ; Patents as Topic ; Research Support as Topic
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  • 98
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-01-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lieberman, P -- New York, N.Y. -- Science. 1999 Jan 8;283(5399):175.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9925475" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Fossils ; Hominidae/*anatomy & histology/physiology ; Humans ; Hyoid Bone/*anatomy & histology ; *Speech ; Tongue/*anatomy & histology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 99
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-04-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davis, D L -- Garry, R F -- New York, N.Y. -- Science. 1999 Mar 12;283(5408):1644.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10189316" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Implants/*adverse effects ; Female ; Humans ; Silicone Gels/*adverse effects
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 100
    Publication Date: 1999-06-12
    Description: Interferons (IFNs) are the most important cytokines in antiviral immune responses. "Natural IFN-producing cells" (IPCs) in human blood express CD4 and major histocompatibility complex class II proteins, but have not been isolated and further characterized because of their rarity, rapid apoptosis, and lack of lineage markers. Purified IPCs are here shown to be the CD4(+)CD11c- type 2 dendritic cell precursors (pDC2s), which produce 200 to 1000 times more IFN than other blood cells after microbial challenge. pDC2s are thus an effector cell type of the immune system, critical for antiviral and antitumor immune responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Siegal, F P -- Kadowaki, N -- Shodell, M -- Fitzgerald-Bocarsly, P A -- Shah, K -- Ho, S -- Antonenko, S -- Liu, Y J -- New York, N.Y. -- Science. 1999 Jun 11;284(5421):1835-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Saint Vincents Hospital and Medical Center, New York, NY 10011, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10364556" target="_blank"〉PubMed〈/a〉
    Keywords: CD40 Ligand ; Cell Lineage ; Cell Separation ; Cells, Cultured ; Dendritic Cells/cytology/*immunology/ultrastructure ; Humans ; Interferon Type I/*biosynthesis ; Interferon-alpha/*biosynthesis/genetics ; Interferon-beta/biosynthesis/genetics ; Interleukin-3/pharmacology ; Leukocytes, Mononuclear/immunology ; Membrane Glycoproteins/pharmacology ; Organelles/ultrastructure ; RNA, Messenger/genetics/metabolism ; Simplexvirus/immunology ; Stem Cells/cytology/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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