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Models for the spatial distribution of protein, lipid and water in gap junction structures have been constructed from the results of the analysis of X-ray diffraction data described here and the electron microscope and chemical data presented in the preceding paper (Caspar, D. L. D., D. A. Goodenough, L. Makowski, and W.C. Phillips. 1977. 74:605-628). The continuous intensity distribution on the meridian of the X-ray diffraction pattern was measured, and corrected for the effects of the partially ordered stacking and partial orientation of the junctions in the X-ray specimens. The electron density distribution in the direction perpendicular to the plane of the junction was calculated from the meridional intensity data. Determination of the interference function for the stacking of the junctions improved the accuracy of the electron density profile. The pair-correlation function, which provides information about the packing of junctions in the specimen, was calculated from the interference function. The intensities of the hexagonal lattice reflections on the equator of the X-ray pattern were used in coordination with the electron microscope data to calculate to the two-dimensional electron density projection onto the plane of the membrane. Differences in the structure of the connexons as seen in the meridional profile and equatorial projections were shown to be correlated to changes in lattice constant. The parts of the junction structure which are variable have been distinguished from the invariant parts by comparison of the X-ray data from different specimens. The combination of these results with electron microscope and chemical data provides low resolution three- dimensional representations of the structures of gap junctions. 相似文献
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The role of nitric oxide in cancer 总被引:4,自引:0,他引:4
WEIMING XU Li ZHI LIU MARILENA LOIZIDOU MOHAMED AHMED IAN G CHARLES Wolfson Institute for Biomedical Research Cruciform Building Gower Street UCL London WC E AUUK Department of Surgery Charles Bell House - Riding House Street UCL London WW EJ UK 《Cell research》2002,(Z2)
Nitric oxide (NO) is a pleiotropic regulator, critical to numerous biological processes, including va-sodilatation, neurotransmission and macrophage-mediated immunity. The family of nitric oxide synthases (NOS) comprises inducible NOS (iNOS), endothelial NOS (eNOS), and neuronal NOS (nNOS). Interestingly, various studies have shown that all three isoforms can be involved in promoting or inhibiting the etiology of cancer. NOS activity has been detected in tumour cells of various histogenetic origins and has been associated with tumour grade, proliferation rate and expression of important signaling components associated with cancer development such as the oestrogen receptor. It appears that high levels of NOS expression (for example, generated by activated macrophages) may be cytostatic or cytotoxic for tumor cells, whereas low level activity can have the opposite effect and promote tumour growth. Paradoxically therefore, NO (and related reactive nitrogen species) may have both genotoxic and angiogenic pro 相似文献
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Paired sequence difference in ribosomal RNAs: evolutionary and phylogenetic implications 总被引:12,自引:1,他引:11
Ribosomal RNAs have secondary structures that are maintained by internal
Watson-Crick pairing. Through analysis of chordate, arthropod, and plant 5S
ribosomal RNA sequences, we show that Darwinian selection operates on these
nucleotide sequences to maintain functionally important secondary
structure. Insect phylogenies based on nucleotide positions involved in
pairing and the production of secondary structure are incongruent with
those constructed on the basis of positions that are not. Furthermore,
phylogeny reconstruction using these nonpairing bases is concordant with
other, morphological data.
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Guido Krebiehl Sabine Ruckerbauer Lena F. Burbulla Nicole Kieper Brigitte Maurer Jens Waak Hartwig Wolburg Zemfira Gizatullina Frank N. Gellerich Dirk Woitalla Olaf Riess Philipp J. Kahle Tassula Proikas-Cezanne Rejko Krüger 《PloS one》2010,5(2)
Background
Mitochondrial dysfunction and degradation takes a central role in current paradigms of neurodegeneration in Parkinson''s disease (PD). Loss of DJ-1 function is a rare cause of familial PD. Although a critical role of DJ-1 in oxidative stress response and mitochondrial function has been recognized, the effects on mitochondrial dynamics and downstream consequences remain to be determined.Methodology/Principal Findings
Using DJ-1 loss of function cellular models from knockout (KO) mice and human carriers of the E64D mutation in the DJ-1 gene we define a novel role of DJ-1 in the integrity of both cellular organelles, mitochondria and lysosomes. We show that loss of DJ-1 caused impaired mitochondrial respiration, increased intramitochondrial reactive oxygen species, reduced mitochondrial membrane potential and characteristic alterations of mitochondrial shape as shown by quantitative morphology. Importantly, ultrastructural imaging and subsequent detailed lysosomal activity analyses revealed reduced basal autophagic degradation and the accumulation of defective mitochondria in DJ-1 KO cells, that was linked with decreased levels of phospho-activated ERK2.Conclusions/Significance
We show that loss of DJ-1 leads to impaired autophagy and accumulation of dysfunctional mitochondria that under physiological conditions would be compensated via lysosomal clearance. Our study provides evidence for a critical role of DJ-1 in mitochondrial homeostasis by connecting basal autophagy and mitochondrial integrity in Parkinson''s disease. 相似文献9.
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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