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排序方式: 共有424条查询结果,搜索用时 15 毫秒
111.
David Schubert Federico Herrera Robert Cumming Jessica Read† William Low† Pamela Maher Wolfgang H. Fischer† 《Journal of neurochemistry》2009,109(2):427-435
Proteins that are released from cells consist of those in the extracellular matrix, as well as extracellular signaling and adhesion molecules. The majority of these extracellular proteins are, however, unknown. To determine their identity, we have used a proteomics approach to define proteins released from neurons, astrocytes and neural precursor cells. Using two-dimensional gels and liquid chromatography/mass spectrometry technology, it is shown that while astrocytes release a relatively small number of proteins, neurons and neuronal precursor cells release a larger number of proteins with more functional diversity. Although there is overlap between the different cell types, the exact composition of the extracellular protein pool is unique for each cell population. The various subsets of extracellular neural proteins include those involved in cellular Redox regulation and chaperones. In addition, many proteolytic enzymes are found outside of the cell. These data show that the extracellular space within the nervous system has a more diverse protein composition than previously thought. 相似文献
112.
Graeme S. Cumming Matthew F. Child 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2009,364(1524):1683-1692
Functional and trophic perspectives on patterns of species occurrences have the potential to offer new and interesting insights into a range of spatially explicit problems in ecology and conservation. We present the function–area relationship (FAR) and explore linkages between functional and taxonomic species richness for South African birds. We first used beak morphology to classify a subset of 151 South African bird species into 18 functional groups and calculated both the species–area relationship and the FAR at quarter-degree resolution for South Africa. The relationship between functional and taxonomic richness by cell was quadratic rather than linear, with considerable scatter around the curve. We next looked at the spatial relationships between taxonomic diversity and response diversity (i.e. diversity within functional groups) using an a priori categorization of nearly all South African birds into nine functional groups. The spatial distribution of response richness also showed considerable variation in relation to taxonomic richness. Our results demonstrate a novel approach to linking taxonomic, functional and trophic patterns in space and suggest a way in which conservation planning, which has traditionally had a taxonomic focus, could formally incorporate a more functional and food-web-based approach. 相似文献
113.
Zoran Rankovic Jiaqiang Cai Jennifer Kerr Xavier Fradera John Robinson Ashvin Mistry Emma Hamilton George McGarry Fiona Andrews Wilson Caulfield Iain Cumming Maureen Dempster John Waller Paul Scullion Iain Martin Ann Mitchell Clive Long Mark Baugh Paul Westwood Emma Kinghorn Eric Nicolai 《Bioorganic & medicinal chemistry letters》2010,20(5):1524-1527
Morphing structural features of HTS-derived chemotypes led to the discovery of novel 2-cyano-pyrimidine inhibitors of cathepsin K with good pharmacokinetic profiles, for example, compound 20 showed high catK potency (IC50 = 4 nM), >580-fold selectivity over catL and catB, and oral bioavailability in the rat of 52%. 相似文献
114.
The Canadian Association for Health, Physical Education and Recreation fitness test (CAHPER test) composed of six items was compared to two laboratory tests of endurance fitness, physical working capacity at a minute pulse rate of 170 (PWC170) and maximum oxygen uptake (Vo2 max.) in over 500 Winnipeg school children of both sexes aged 6 to 17 years. CAHPER test results were similar to the national average published by CAHPER in a test booklet. Correlation coefficients (r) of Vo2 max. for boys with the CAHPER tests were: sit-ups .42, broad jump .69, shuttle run .50, arm hang .43, 50-yard dash .60, 300-yard run .65; for girls the r values were about half the values for the boys. Much of the correlation between CAHPER tests and Vo2 max. or PWC170 depended on the association of each test with body size. When multiple correlations were obtained including surface area as the first variable, the only significant factor correlating with the endurance tests was the arm hang; none of the other tests showed a significant correlation. “Physical fitness” is task-specific, so that a subject''s position in the scoring scale of a fitness test depends entirely upon the test. The CAHPER test for physical fitness shows little or no correlation with standard laboratory measures of endurance in average children. 相似文献
115.
116.
The African savanna biome supports a higher diversity of ungulate species than is found in any other biome or continent. This exceptional faunal diversity and herbivore biomass density is directly linked to the high spatial heterogeneity of African savanna ecosystems. The dependence of herbivore dietary tolerance on body size translates into important size-related differences between savanna ungulate species in terms of habitat specificity, geographical range, and the share of community resources exploited. Intact savanna ungulate communities, with species distributed across body size classes and feeding guilds (grazer/browser), have strong regulatory influences on savanna ecosystem structure and function. Replacement with livestock systems of low diversity and high biomass density within a narrow body size range has occurred through the removal of competitors, pathogens, and predators, and the widespread provisioning of water. Overgrazing by livestock, coupled with episodic droughts, has caused widespread rangeland degradation and loss of floristic and faunal diversity which, by current models, is unlikely to recover to 'climax conditions even with destocking. In selected regions where potential still exists, African savanna biodiversity and human economic development will both be best served by the integration of sustainable wildlife utilization into multispecies animal production systems. 相似文献
117.
Cumming RC Andon NL Haynes PA Park M Fischer WH Schubert D 《The Journal of biological chemistry》2004,279(21):21749-21758
The majority of disulfide-linked cytosolic proteins are thought to be enzymes that transiently form disulfide bonds while catalyzing oxidation-reduction (redox) processes. Recent evidence indicates that reactive oxygen species can act as signaling molecules by promoting the formation of disulfide bonds within or between select redox-sensitive proteins. However, few studies have attempted to examine global changes in disulfide bond formation following reactive oxygen species exposure. Here we isolate and identify disulfide-bonded proteins (DSBP) in a mammalian neuronal cell line (HT22) exposed to various oxidative insults by sequential nonreducing/reducing two-dimensional SDS-PAGE combined with mass spectrometry. By using this strategy, several known cytosolic DSBP, such as peroxiredoxins, thioredoxin reductase, nucleoside-diphosphate kinase, and ribonucleotide-diphosphate reductase, were identified. Unexpectedly, a large number of previously unknown DSBP were also found, including those involved in molecular chaperoning, translation, glycolysis, cytoskeletal structure, cell growth, and signal transduction. Treatment of cells with a wide range of hydrogen peroxide concentrations either promoted or inhibited disulfide bonding of select DSBP in a concentration-dependent manner. Decreasing the ratio of reduced to oxidized glutathione also promoted select disulfide bond formation within proteins from cytoplasmic extracts. In addition, an epitope-tagged version of the molecular chaperone HSP70 forms mixed disulfides with both beta4-spectrin and adenomatous polyposis coli protein in the cytosol. Our findings indicate that disulfide bond formation within families of cytoplasmic proteins is dependent on the nature of the oxidative insult and may provide a common mechanism used to control multiple physiological processes. 相似文献
118.
Stewart JD Masi TL Cumming AE Molnar GM Wentworth BM Sampath K McPherson JM Yaeger PC 《Journal of cellular physiology》2003,196(1):70-78
Adult human skeletal muscle-derived cells (HuSkMC) propagated in vitro are under investigation as a cell-based therapy for the treatment of myocardial infarction. We have characterized HuSkMC with respect to cell identity and state of differentiation as a prerequisite to their clinical use. Flow cytometric analysis of propagated HuSkMC revealed a population of cells that expressed the myoblast markers CD56 and desmin. The presence of myoblasts in these cultures was further confirmed by their capacity to form myotubes and increase creatine kinase activity when cultured in low serum conditions. The non-myoblast fraction of these propagated cells expressed TE7, a marker associated with the fibroblast phenotype. Spontaneous differentiation of myoblasts occurred during serial propagation of HuSkMC, as judged by myotube formation, thereby reducing the myoblast representative fraction with continued cell expansion. We examined transforming growth factor beta2 (TGF-beta2) for its utility in controlling this spontaneous differentiation of adult human myoblasts in vitro. Propagation of HuSkMC in the presence of 1 ng/ml TGF-beta2 for 5 days decreased desmin expression within the myoblast population and caused a parallel reduction of creatine kinase activity. CD56 expression was unaffected, indicating a differential regulation of these myoblast markers. The reduction in desmin expression and creatine kinase activity was, however, reversible upon the removal of TGF-beta. These data collectively indicate that TGF-beta2 restrained differentiation of adult human skeletal myoblasts during propagation without causing irreversible loss of the myoblast phenotype, demonstrating the potential utility of using TGF-beta2 during cultivation and expansion of HuSkMC intended for therapeutic implantation. 相似文献
119.
The objective of this work was to apply artificial neural networks (ANNs) to examine the relative importance of various factors,
both formulation and process, governing the in-vitro dissolution from enteric-coated sustained release (SR) minitablets. Input
feature selection (IFS) algorithms were used in order to give an estimate of the relative importance of the various formulation
and processing variables in determining minitablet dissolution rate. Both forward and backward stepwise algorithms were used
as well as genetic algorithms. Networks were subsequently trained using the back propagation algorithm in order to check whether
or not the IFS process had correctly located any unimportant inputs. IFS gave consistent rankings for the importance of the
various formulation and processing variables in determining the release of drug from minitablets. Consistent ranking was achieved
for both indices of the release process; ie, the time taken for release to commence through the enteric coat (Tlag) and that for the drug to diffuse through the SR matrix of the minitablet into the dissolution medium (T90-10). In the case of the Tlag phase, the main coating parameters, along with the original batch blend size and the blend time with lubricant, were found
to have most influence. By contrast, with the T90-10 phase, the amounts of matrix forming polymer and direct compression filler were most important. In the subsequent training
of the ANNs, removal of inputs regarded as less important led to improved network performance. ANNs were capable of ranking
the relative importance of the various formulations and processing variables that influenced the release rate of the drug
from minitablets. This could be done for all main stages of the release process. Subsequent training of the ANN verified that
removal of less relevant inputs from the training process led to an improved performance from the ANN. 相似文献
120.
R C Cumming J Lightfoot K Beard H Youssoufian P J O'Brien M Buchwald 《Nature medicine》2001,7(7):814-820
The Fanconi anemia group C protein (FANCC) plays an important role in hematopoiesis by ensuring the survival of hematopoietic progenitor cells through an unknown mechanism. We investigated the function of FANCC by identifying FANCC-binding proteins in hematopoietic cells. Here we show that glutathione S-transferase P1-1 (GSTP1) interacts with FANCC, and that overexpression of both proteins in a myeloid progenitor cell line prevents apoptosis following factor deprivation. FANCC increases GSTP1 activity after the induction of apoptosis. GSTP1 is an enzyme that catalyzes the detoxification of xenobiotics and by-products of oxidative stress, and it is frequently upregulated in neoplastic cells. Although FANCC lacks homology with conventional disulfide reductases, it functions by preventing the formation of inactivating disulfide bonds within GSTP1 during apoptosis. The prevention of protein oxidation by FANCC reveals a novel mechanism of enzyme regulation during apoptosis and has implications for the treatment of degenerative diseases with thiol reducing agents. 相似文献