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There is growing interest in the proteins involved in protein folding. This is mainly due to the large number of human diseases related to defects in folding, which include cystic fibrosis, Alzheimer's and cancer. However, equally important as the oxidation and concomitant formation of disulfide bridges of the extracellular or secretory proteins is the reduction and maintenance in the reduced state of the proteins within the cell. Interestingly, the proteins that are responsible for maintenance of the reduced state belong to the same superfamily as those responsible for the formation of disulfide bridges: all are members of the thioredoxin superfamily. In this article, we highlight the main features of those thioredoxin-like proteins directly involved in the redox reactions. We describe their biological functions, cytoplasmic location, mechanisms of action, structures and active site features, and discuss the principal hypotheses concerning origins of the different reduction potentials and unusual pKa's of the catalytic residues.  相似文献   

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Brain recovery after prolonged wakefulness is characterized by increased density, amplitude and slope of slow waves (SW, <4 Hz) during non-rapid eye movement (NREM) sleep. These SW comprise a negative phase, during which cortical neurons are mostly silent, and a positive phase, in which most neurons fire intensively. Previous work showed, using EEG spectral analysis as an index of cortical synchrony, that Morning-types (M-types) present faster dynamics of sleep pressure than Evening-types (E-types). We thus hypothesized that single SW properties will also show larger changes in M-types than in E-types in response to increased sleep pressure. SW density (number per minute) and characteristics (amplitude, slope between negative and positive peaks, frequency and duration of negative and positive phases) were compared between chronotypes for a baseline sleep episode (BL) and for recovery sleep (REC) after two nights of sleep fragmentation. While SW density did not differ between chronotypes, M-types showed higher SW amplitude and steeper slope than E-types, especially during REC. SW properties were also averaged for 3 NREM sleep periods selected for their decreasing level of sleep pressure (first cycle of REC [REC1], first cycle of BL [BL1] and fourth cycle of BL [BL4]). Slope was significantly steeper in M-types than in E-types in REC1 and BL1. SW frequency was consistently higher and duration of positive and negative phases constantly shorter in M-types than in E-types. Our data reveal that specific properties of cortical synchrony during sleep differ between M-types and E-types, although chronotypes show a similar capacity to generate SW. These differences may involve 1) stable trait characteristics independent of sleep pressure (i.e., frequency and durations) likely linked to the length of silent and burst-firing phases of individual neurons, and 2) specific responses to increased sleep pressure (i.e., slope and amplitude) expected to depend on the synchrony between neurons.  相似文献   

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The most prominent EEG events in sleep are slow waves, reflecting a slow (<1 Hz) oscillation between up and down states in cortical neurons. It is unknown whether slow oscillations are synchronous across the majority or the minority of brain regions--are they a global or local phenomenon? To examine this, we recorded simultaneously scalp EEG, intracerebral EEG, and unit firing in multiple brain regions of neurosurgical patients. We find that most sleep slow waves and the underlying active and inactive neuronal states occur locally. Thus, especially in late sleep, some regions can be active while others are silent. We also find that slow waves can propagate, usually from medial prefrontal cortex to the medial temporal lobe and hippocampus. Sleep spindles, the other hallmark of NREM sleep EEG, are likewise predominantly local. Thus, intracerebral communication during sleep is constrained because slow and spindle oscillations often occur out-of-phase in different brain regions.  相似文献   

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Growth and ploidy of rat ventricular myocytes were studied during development in situ and in grafts (1 day old rat ventricle transplanted under kidney capsule of syngenic adult animals). Both in situ and in the transplants polyploidization occurred on days 4-14 of postnatal life, and the modal group of myocytes was represented by binucleate diploid (2c x 2) cells. Minor quantities of 4c, 4c x 2, 8c and 2c x 4 myocytes were detected as well. In ventricles of 14 and 28 days old rats and in the transplants of the corresponding age the portion of polyploid myocytes was 90-96% and 32-63% respectively. The intensity of postmitotic myocyte transplants was decreased as compared with in situ development, and cells that exit proliferation cycle did not grow until day 14. The data on thymidine label dilution suggest that diploid myocytes of the transplant can divide two or three times but the majority of labeled diploids divided only once. Labeled 2c x 2 myocytes originated from the first, and less frequently, the second cell generation or resulted from initial acytokinetic mitosis. Mononucleate tetraploids 4c originated from 2c x 2 and mostly from 2c cells. Octaploids were formed after 3d or 4th labeled mitosis. The conclusion about cardiac myocyte polyploidization as an intrinsic developmental program is supported, implying the programming of onset, mode, duration and termination of polyploidization and its prolongation during early postnatal life.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

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MOTIVATION AND METHODS: All living organisms and the survival of all cells critically depend on their ability to sense and quickly adapt to changes in the environment and to other stress conditions. We study stress response mechanisms in Saccharomyces cerevisiae by identifying genes that, according to very stringent criteria, have persistent co-expression under a variety of stress conditions. This is enabled through a fast clique search method applied to the intersection of several co-expression graphs calculated over the data of Gasch et al. This method exploits the topological characteristics of these graphs. RESULTS: We observe cliques in the intersection graphs that are much larger than expected under a null model of changing gene identities for different stress conditions but maintaining the co-expression topology within each one. Persistent cliques are analyzed to identify enriched function as well as enriched regulation by a small number of TFs. These TFs, therefore, characterize a universal and persistent reaction to stress response. We further demonstrate that the vertices (genes) of many cliques in the intersection graphs are co-localized in the yeast genome, to a degree far beyond the random expectation. Co-localization can hypothetically contribute to a quick co-ordinated response. We propose the use of persistent cliques in further study of properties of co-regulation.  相似文献   

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One of the key features in development is the reutilization of successful signaling pathways. Here, we emphasize the involvement of the Wnt pathway, one of the five kinds of signal transduction pathway predominating early embryonic development of all animals, in regulating the formation of brain structure. We discuss the interrelationships between the Wnt and reelin pathways in the regulation of cortical layering. We summarize data emphasizing key molecules, which, when mutated, result in abnormal brain development. This integrated view, which is based on conservation of pathways, reveals the relative position of participants in the pathway, points to control mechanisms, and allows raising testable working hypotheses. Nevertheless, although signaling pathways are highly conserved from flies to humans, the overall morphology is not. We propose that future studies directed at understanding of diversification will provide fruitful insights on mammalian brain formation.  相似文献   

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Similarities and differences in rubber biochemistry among plant species.   总被引:9,自引:0,他引:9  
K Cornish 《Phytochemistry》2001,57(7):1123-1134
This report reviews aspects of the biochemical regulation of rubber yield and rubber quality in three contrasting rubber-producing species, Hevea brasiliensis, Parthenium argentatum and Ficus elastica. Although many similarities are revealed, considerable differences also exist in enzymatic mechanisms regulating biosynthetic rate and the molecular weight of the rubber biopolymers produced. In all three species, rubber molecule initiation, biosynthetic rate and molecular weight, in vitro, are dependent upon substrate concentration and the ratio of isopentenyl pyrophosphate (IPP, the elongation substrate, or monomer) and farnesyl pyrophosphate (FPP, an initiator), but these parameters are affected by intrinsic properties of the rubber transferases as well. All three rubber transferases are capable of producing a wide range of rubber molecular weight, depending upon substrate concentration, clearly demonstrating that the transferases are not the prime determinants of product size in vivo. However, despite these commonalities, considerable differences exist between the species with respect to cosubstrate effects, binding constants, effective concentration ranges, and the role of negative cooperativity in vitro. The P. argentatum rubber transferase appears to exert more control over the molecular weight it produces than the other two species and may, therefore, provide the best prospect for the source of genes for transformation of annual crop species.The kinetic data, from the three contrasting rubber-producing species, also were used to develop a model of the rubber transferase active site in which, in addition to separate IPP and allylic-PP binding sites, there exists a hydrophobic region that interacts with the linear portion of allylic-PP initiator proximal to the pyrophosphate. Substrate affinity increases until the active site is traversed and the rubber interior of the rubber particle is reached. The kinetic data suggest that the hydrophobic region in H. brasiliensis and F. elastica is about 1.8 nm long but only 1.3 nm in P. argentatum. The estimates are supported by measurements of the rubber particle monolayer membrane using electron paramagnetic resonance spectroscopy.  相似文献   

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Rabbit skeletal tropomyosin was separated into two components, alpha and beta, by CM cellulose column chromatography in the presence of urea. The two components are apparently different from TN-T, since, 1) upon addition of the components to F-actin solutions, they increase the degree of flow birefringence delta n, while TN-T does not, 2) the reduced mean residue elipticities [theta] at 220 nm are about 2.5-fold higher than for TN-T, and they contain no proline. These features are similar to those of intact tropomyosin, but the two components are not identical for the following reasons; 1) leucine is the C-terminus of the beta component and isoleucine is the C-terminus of the alpha component, 2) the beta component has a lower helicity and a somewhate lower capacity to increase delta n of F-actin solutions than the alpha component, and 3) the beta component has a higher content of glutamic acid and methionine than the alpha component. The two components can be crystallized into paracrystals in the presence of magnesium. Electron micrographs of the paracrystals of both components show a band pattern with 400 A periodicity. Bovine cardiac tropomyosin migrates on SDS gels as two poorly resolved bands, which could be separated by CM cellulose column chromatography. The C-terminus of the slower moving component was leucine, and that of the faster moving component was isoleucine, corresponding to the beta and alpha components of skeletal tropomyosin.  相似文献   

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W Kromer  W Pretzlaff  R Woinoff 《Life sciences》1980,26(22):1857-1865
The influence of opioid receptor blockade by naloxone and opioid receptor activation by opioids on peristalsis was studied in isolated segments of the guinea pig ileum.1. (-)Naloxone, but not (+)naloxone, increased the mean number of peristaltic waves per min within periods of elevated intraluminal pressure. Naloxone tended to modify intermittent peristalsis into ongoing peristalsis, whereas opioids worked in an opposite fashion. 2. Maximum amplitudes of luminal volume displacement during single peristaltic waves were not decreased by opioids. (-)Naloxone, however, applied to non-pretreated segments, decreased transitorily the efficacy of single peristaltic waves to a small, but statistically significant degree 3. Enhancement of peristalsis by naloxone decreased over time, although enough naloxone was present to occupy all opioid receptors. This suggests that opioid receptor blockade induces some compensatory mechanism.  相似文献   

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Tau protein and Chromobindin A have several features in common but are not identical. Both consist of a small group of closely related proteins which can form aggregates. Both have a similar range of molecular weights (53–62 kDa) and isoelectric points (6.0–7.5). While Chromobindin A is known to be membrane associated, there is evidence that Tau protein also interacts with phospholipids. Both, not present in all tissues, can be found in the adrenal medulla. Despite these similarities both classes of proteins are unique and immunologically distinct. A rabbit antisera to Tau does not cross react with Chromobindin A. In addition, while protein kinase C and Ca/Calmodulin-dependent protein kinase II phosphorylate Tau protein, they do not phosphorylate Chromobindin A, demonstrating the specificity of these kinases for Tau protein phosphorylation.  相似文献   

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Fibronectins from normal and virally transformed hamster cells were compared by several criteria. The fibronectin from transformed cells was similar to that from normal cells in being an intact dimeric glycoprotein with the ability to bind to gelatin, activated thiol-Sepharose, and cells. No evidence was found for proteolytic cleavages or abnormalities in disulfide bonding of transformed cell fibronectin. This fibronectin was also shown to be active in promoting cell attachment, elongation, and alignment. Therefore, the fibronectin produced by transformed cells is not defective. However, it was shown that the transformed cells were partially deficient in their capacity to bind fibronectins from either normal or transformed cells. This deficiency has implications for the significance of the loss of fibronectin on oncogenic transformation. Partial proteolysis of the fibronectins from normal and transformed cells gave rise to the same fragments. However, the glycosylated fragments from transformed cell fibronectin appeared somewhat larger than those from normal cell fibronectin. Analysis of fibronectin glycopeptides showed that transformation leads both to more branches per core and to a higher sialylation of the asparagine-linked complex carbohydrate side chains.  相似文献   

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《Free radical research》2013,47(11-12):1267-1278
Abstract

Hyperbaric oxygen (HBO) treatment is based on the principle of having the patient breath 100% oxygen in an environment above atmospheric pressure. Ozone (O3) is a colourless gas with a specific odour and consists of three oxygen atoms. The classical scientific understanding is that the world has become a place suitable for life for aerobic organisms with the increasing oxygen in the atmosphere billions of years ago. The formation of ozone after oxygen has then protected aerobic creatures from harmful rays. We now use these two gases for treatment purposes. It is noteworthy that the oxygen and ozone molecules that are formed by the same atom in different numbers are used for similar medical indications. We will try to emphasize the similarities and differences of HBO and medical ozone applications in this article.  相似文献   

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