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71.
Osteogenic sarcoma (osteosarcoma) is the most common primary tumor of bone. It accounts for approximately 19% of all malignant tumors of the bone. Of all the molecular targets altered during the genesis of osteosarcoma, the retinoblastoma gene (RB1) shows the highest frequency of inactivation. Published data from human osteosarcoma tumors and in vivo and in vitro model systems support a role for the retinoblastoma gene family in bone development and tumorigenesis. Although a variety of bone tumors, depending on the cell of origin, including osteoclasts or osteoclast-like cells, chondroblasts, and fibroblasts, are described, for the purpose of this review we will focus primarily on the tumors arising from the osteoblast lineage. 相似文献
72.
Cellular senescence is a tumor-suppressive process instigated by proliferation in the absence of telomere replication, by cellular stresses such as oncogene activation, or by activation of the retinoblastoma tumor suppressor protein, pRb. This process is characterized by an irreversible cell cycle exit, a unique morphology, and expression of senescence-associated-beta-galactosidase (SA-beta-gal). Despite the potential biological importance of cellular senescence, little is known of the mechanisms leading to the senescent phenotype. We have recently discovered that expression of active pRb induces expression and altered localization of the ERM family member ezrin, an actin-binding protein involved in membrane-cytoskeletal signaling. pRb expression results in the stimulation of cdk5-mediated phosphorylation of ezrin with subsequent membrane association and induction of cell shape changes, linking pRb activity to cytoskeletal regulation in senescent cells. Cdk5 activity increases in senescing cells and is required for expression of SA-beta-gal and for actin polymerization accompanying acquisition of the senescent morphology. These results begin to illuminate the mechanisms underlying induction of senescence and the senescent shape change and describe new pathways that may contribute to the ability of senescent cells to influence tumor growth. 相似文献
73.
Hinds P 《Biochimica et biophysica acta》1999,1423(2):R63-R67
74.
Using a DNA microarray to investigate the distribution of insect virulence factors in strains of photorhabdus bacteria 下载免费PDF全文
Marokhazi J Waterfield N LeGoff G Feil E Stabler R Hinds J Fodor A ffrench-Constant RH 《Journal of bacteriology》2003,185(15):4648-4656
Photorhabdus is an insect-pathogenic bacterium in which oral toxicity to insects is found in two distinct taxonomic groups. Using a DNA microarray and comparative genomics, we show that oral toxicity is associated with toxin complex genes tcaABC and that this locus can be mobilized or deleted within different strains. 相似文献
75.
Structure of the Alzheimer's disease amyloid precursor protein copper binding domain. A regulator of neuronal copper homeostasis 总被引:3,自引:0,他引:3
Barnham KJ McKinstry WJ Multhaup G Galatis D Morton CJ Curtain CC Williamson NA White AR Hinds MG Norton RS Beyreuther K Masters CL Parker MW Cappai R 《The Journal of biological chemistry》2003,278(19):17401-17407
A major source of free radical production in the brain derives from copper. To prevent metal-mediated oxidative stress, cells have evolved complex metal transport systems. The Alzheimer's disease amyloid precursor protein (APP) is a major regulator of neuronal copper homeostasis. APP knockout mice have elevated copper levels in the cerebral cortex, whereas APP-overexpressing transgenic mice have reduced brain copper levels. Importantly, copper binding to APP can greatly reduce amyloid beta production in vitro. To understand this interaction at the molecular level we solved the structure of the APP copper binding domain (CuBD) and found that it contains a novel copper binding site that favors Cu(I) coordination. The surface location of this site, structural homology of CuBD to copper chaperones, and the role of APP in neuronal copper homeostasis are consistent with the CuBD acting as a neuronal metallotransporter. 相似文献
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Davet Julien; Clavel Benoit; Datas Lucien; Mani-Ponset Laurence; Maurel Daniel; Herbute Serge; Viso Michel; Hinds William; Jarvi Joellen; Gabrion Jacqueline 《Journal of applied physiology》1998,84(1):19-29
Davet, Julien, Benoit Clavel, Lucien Datas, LaurenceMani-Ponset, Daniel Maurel, Serge Herbuté, Michel Viso, WilliamHinds, Joellen Jarvi, and Jacqueline Gabrion.Choroidal readaptation to gravity in rats after spaceflight andhead-down tilt. J. Appl. Physiol.84(1): 19-29, 1998.To determine when choroidal structures wererestored after readaptation to Earth gravity or orthostatic position,fine structure and protein distribution were studied in rat choroidplexus dissected either 6 h [Space Life Sciences-2 (SLS-2)experiments] or 2 days [National Institutes ofHealth-Rodent 1 (NIH-R1) experiments] after a spaceflight, or 6 hafter head-down tilt (HDT) experiments. Apical alterations were notedin choroidal cells from SLS-2 and HDT animals, confirming thatweightlessness impaired choroidal structures and functions. However,the presence of small apical microvilli and kinocilia and the absenceof vesicle accumulations showed that the apical organization began tobe restored rapidly after landing. Very enlarged apical microvilli appeared after 2 days on Earth, suggesting increased choroidal activity. However, as distributions of ezrin and carbonic anhydrase IIremained altered in both flight and suspended animals after readaptation to Earth gravity, it was concluded that choroidal structures and functions were not completely restored, even after 2 days in Earth's gravity. 相似文献
80.
Mitochondrial gene order is not conserved in arthropods: prostriate and metastriate tick mitochondrial genomes 总被引:25,自引:15,他引:10
The entire mitochondrial genome was sequenced in a prostriate tick, Ixodes
hexagonus, and a metastriate tick, Rhipicephalus sanguineus. Both genomes
encode 22 tRNAs, 13 proteins, and two ribosomal RNAs. Prostriate ticks are
basal members of Ixodidae and have the same gene order as Limulus
polyphemus. In contrast, in R. sanguineus, a block of genes encoding NADH
dehydrogenase subunit 1 (ND1), tRNA(Leu)(UUR), tRNA(Leu)(CUN), 16S rDNA,
tRNA(Val), 12S rDNA, the control region, and the tRNA(Ile) and tRNA(Gln)
have translocated to a position between the tRNA(Glu) and tRNA(Phe) genes.
The tRNA(Cys) gene has translocated between the control region and the
tRNA(Met) gene, and the tRNA(Leu)(CUN) gene has translocated between the
tRNA(Ser)(UCN) gene and the control region. Furthermore, the control region
is duplicated, and both copies undergo concerted evolution. Primers that
flank these rearrangements confirm that this gene order is conserved in all
metastriate ticks examined. Correspondence analysis of amino acid and codon
use in the two ticks and in nine other arthropod mitochondrial genomes
indicate a strong bias in R. sanguineus towards amino acids encoded by
AT-rich codons.
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