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61.
Steinlechner S Jacobmeier B Scherbarth F Dernbach H Kruse F Albrecht U 《Journal of biological rhythms》2002,17(3):202-209
The Per1 and Per2 genes are components of the mammalian circadian clock. Mutations in these genes alter phase resetting in response to a nocturnal light pulse, and Per2 mutant mice are known to become arrhythmic in constant darkness. We show that under constant light conditions, Per2 mutant mice exhibit robust activity rhythms as well as body temperature rhythms with a period length that is less than 24 h. In Per1 mutants, the period length of both activity and body temperature rhythms is longer than 24 h in constant light. Per1 mutants prolong their period length (tao) when illuminance is increased, whereas Per2 mutants shorten their endogenous period. Additionally, the authors show that the circadian pattern of Per1 and Per2 gene expression in mice is modified under different photoperiods and that there is a mutual influence of these genes on their timing of expression. We propose that, in mice, the phase relationship between Per1 and Per2 gene expression might be critical for transducing day length information to the organism. Per1 could be part of a morning oscillator tracking dawn, and Per2 could be part of an evening oscillator tracking dusk. 相似文献
62.
Mabit H Nakano MY Prank U Saam B Döhner K Sodeik B Greber UF 《Journal of virology》2002,76(19):9962-9971
Capsids and the enclosed DNA of adenoviruses, including the species C viruses adenovirus type 2 (Ad2) and Ad5, and herpesviruses, such as herpes simplex virus type 1 (HSV-1), are targeted to the nuclei of epithelial, endothelial, fibroblastic, and neuronal cells. Cytoplasmic transport of fluorophore-tagged Ad2 and immunologically detected HSV-1 capsids required intact microtubules and the microtubule-dependent minus-end-directed motor complex dynein-dynactin. A recent study with epithelial cells suggested that Ad5 was transported to the nucleus and expressed its genes independently of a microtubule network. To clarify the mechanisms by which Ad2 and, as an independent control, HSV-1 were targeted to the nucleus, we treated epithelial cells with nocodazole (NOC) to depolymerize microtubules and measured viral gene expression at different times and multiplicities of infections. Our results indicate that in NOC-treated cells, viral transgene expression was significantly reduced at up to 48 h postinfection (p.i.). A quantitative analysis of subcellular capsid localization indicated that NOC blocked the nuclear targeting of Ad2 and also HSV-1 by more than 90% at up to 7 h p.i. About 10% of the incoming Texas Red-coupled Ad2 (Ad2-TR) was enriched at the nucleus in microtubule-depleted cells at 5 h p.i. This result is consistent with earlier observations that Ad2-TR capsids move randomly in NOC-treated cells at less than 0.1 micro m/s and over distances of less than 5 micro m, characteristic of Brownian motion. We conclude that fluorophore-tagged Ad2 and HSV-1 particles are infectious and that microtubules play a prominent role in efficient nuclear targeting during entry and gene expression of species C Ads and HSV-1. 相似文献
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In addition to protein identification, characterization of post-translational modifications (PTMs) is an essential task in proteomics. PTMs represent the major reason for the variety of protein isoforms and they can influence protein structure and function. Upon matrix-assisted laser desorption/ionization (MALDI) most post-translationally modified peptides form a fraction of labile molecular ions, which lose PTM-specific residues only after acceleration. Compared to fully accelerated ions these fragment ions are defocused and show in reflector mass spectra reduced resolution. A short time Fourier transform using a Hanning window function now uses this difference in resolution to detect the metastable fragments. Its application over the whole mass range yields frequency distributions and amplitudes as a function of mass, where an increased low frequency proportion is highly indicative for metastable fragments. Applications on the detection of metastable losses originating from carboxamidomethylated cysteines, oxidized methionines, phosphorylated and glycosylated amino acid residues are presented. The metastable loss of mercaptoacetamide detected with this procedure represents a new feature and its integration in search algorithms will improve the specificity of MALDI peptide mass fingerprinting. 相似文献
65.
Reynald Olivier Urs Scherrer Jean-Daniel Horisberger Bernard C Rossier Edith Hummler 《Journal of applied physiology》2002,93(5):1881-1887
The amiloride-sensitive epithelial Na(+) channel (ENaC) is essential for fluid clearance from the airways. An experimental animal model with a reduced expression of ENaC, the alpha-ENaC transgenic rescue mouse, is prone to develop edema under hypoxia exposure. This strongly suggests an involvement of ENaC in the pathogenesis of pulmonary edema. To investigate the pathogenesis of this type of edema, primary cultures of tracheal cells from these mice were studied in vitro. An ~60% reduction in baseline amiloride-sensitive Na(+) transport was observed, but the pharmacological characteristics and physiological regulation of the channel were similar to those observed in cells from wild-type mice. Aprotinin, an inhibitor of serine proteases, blocked 50-60% of the basal transepithelial current, hypoxia induced downregulation of Na(+) transport, and beta-adrenergic stimulation was effective to stimulate Na(+) transport after the hypoxia-induced decrease. When downregulation of ENaC activity (such as observed under hypoxia) is added to a low "constitutive" ENaC expression, the resulting reduced Na(+) transport rate may be insufficient for airway fluid clearance and favor pulmonary edema. 相似文献
66.
Some misprints appeared on page 640, in Table II and in the last paragraph of Section 2.2 (line 9). One should read: "3.075 × 10-2", "-4.900 × 10-4", "1.440 × 10-5", "2.500 × 10-9" and "1.0 × 10-8", respectively (there are not exponential functions). 相似文献
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The case of a boy with Prader-Willi syndrome (PWS) who suffered from respiratory problems since birth and suddenly died at the age of 6.5 years, 4 months after initiation of GH therapy, is presented. This case indicates the possibility of fatal courses in infants and children with PWS as a consequence of respiratory problems and raises the question as to a causal connection between the initiation of GH therapy and the sudden death of this child. 相似文献
69.
70.
Meier O Boucke K Hammer SV Keller S Stidwill RP Hemmi S Greber UF 《The Journal of cell biology》2002,158(6):1119-1131
Adenovirus type 2 (Ad2) binds the coxsackie B virus Ad receptor and is endocytosed upon activation of the alphav integrin coreceptors. Here, we demonstrate that expression of dominant negative clathrin hub, eps15, or K44A-dynamin (dyn) inhibited Ad2 uptake into epithelial cells, indicating clathrin-dependent viral endocytosis. Surprisingly, Ad strongly stimulated the endocytic uptake of fluid phase tracers, coincident with virus internalization but without affecting receptor-mediated transferrin uptake. A large amount of the stimulated endocytic activity was macropinocytosis. Macropinocytosis depended on alphav integrins, PKC, F-actin, and the amiloride-sensitive Na+/H+ exchanger, which are all required for Ad escape from endosomes and infection. Macropinocytosis stimulation was not a consequence of viral escape, since it occurred in K44A-dyn-expressing cells. Surprisingly, 30-50% of the endosomal contents were released into the cytosol of control and also K44A-dyn-expressing cells, and the number of fluid phase-positive endosomes dropped below the levels of noninfected cells, indicating macropinosomal lysis. The release of macropinosomal contents was Ad dose dependent, but the presence of Ad particles on macropinosomal membranes was not sufficient for contents release. We conclude that Ad signaling from the cell surface controls the induction of macropinosome formation and leakage, and this correlates with viral exit to the cytosol and infection. 相似文献