排序方式: 共有39条查询结果,搜索用时 15 毫秒
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Catherine E. Winbanks Justin L. Chen Hongwei Qian Yingying Liu Bianca C. Bernardo Claudia Beyer Kevin I. Watt Rachel E. Thomson Timothy Connor Bradley J. Turner Julie R. McMullen Lars Larsson Sean L. McGee Craig A. Harrison Paul Gregorevic 《The Journal of cell biology》2013,203(2):345-357
Although the canonical transforming growth factor β signaling pathway represses skeletal muscle growth and promotes muscle wasting, a role in muscle for the parallel bone morphogenetic protein (BMP) signaling pathway has not been defined. We report, for the first time, that the BMP pathway is a positive regulator of muscle mass. Increasing the expression of BMP7 or the activity of BMP receptors in muscles induced hypertrophy that was dependent on Smad1/5-mediated activation of mTOR signaling. In agreement, we observed that BMP signaling is augmented in models of muscle growth. Importantly, stimulation of BMP signaling is essential for conservation of muscle mass after disruption of the neuromuscular junction. Inhibiting the phosphorylation of Smad1/5 exacerbated denervation-induced muscle atrophy via an HDAC4-myogenin–dependent process, whereas increased BMP–Smad1/5 activity protected muscles from denervation-induced wasting. Our studies highlight a novel role for the BMP signaling pathway in promoting muscle growth and inhibiting muscle wasting, which may have significant implications for the development of therapeutics for neuromuscular disorders. 相似文献
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Background
Experimentally determined protein structures may contain errors and require validation. Conformational criteria based on the Ramachandran plot are mainly used to distinguish bet ween distorted and adequately refined models. While the readily available criteria are sufficient to detect totally wrong structures, establishing the more subtle differences between plausible structures remains more challenging. 相似文献24.
Background
Estimators of free energies are routinely used to judge the quality of protein structural models. As these estimators still present inaccuracies, they are frequently evaluated by discriminating native or native-like conformations from large ensembles of so-called decoy structures. 相似文献25.
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Role of the phosphatidylinositol 3-kinase and mTOR pathways in the regulation of renal fibroblast function and differentiation 总被引:3,自引:0,他引:3
Winbanks CE Grimwood L Gasser A Darby IA Hewitson TD Becker GJ 《The international journal of biochemistry & cell biology》2007,39(1):206-219
Tubulointerstitial fibrosis is largely mediated by (myo)fibroblasts present in the interstitium. In this study, we investigated the role of mTOR and phosphatidylinositol 3-kinase in the regulation of fibroblast kinetics, fibroblast differentiation, and collagen synthesis. Rat renal fibroblasts were propagated from kidneys 3 days post-ureteric obstruction and specific inhibitors of mTOR (RAD) and phosphatidylinositol 3-kinase (LY294002) were used to examine the regulation of fibrogenesis. LY294002 but not RAD completely inhibited phosphorylation of Akt, while both inhibitors decreased phosphorylation of the S6 ribosomal protein. RAD and LY decreased foetal calf serum stimulated proliferation and DNA synthesis. In addition to their individual effects, treatment with both RAD and LY294002 decreased serum-induced fibroblast proliferation and DNA synthesis significantly more than either drug alone. TUNEL positive cells (apoptosis) in RAD and LY294002 treated groups were not different from control groups. In addition to their effect on proliferation, both inhibitors also reduced total collagen synthesis. Differentiation studies indicated an increase in alpha-smooth muscle actin expression relative to beta-actin (western blotting), with cytochemistry confirming that all doses of RAD and LY294002 increased the proportion of alpha-smooth muscle actin positive cells, and hence myofibroblasts. Effects were independent of cell toxicity. These results highlight the potential significance of PI3K and mTOR, in the regulation of renal (myo)fibroblast activity. The synergistic effects of LY and RAD on proliferation suggest that mTOR signalling involves pathways other than phosphatidylinositol 3-kinase. These results provide a novel insight into the mechanisms of fibroblast regulation during fibrogenesis. 相似文献
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The taste of polycose in hamsters 总被引:2,自引:2,他引:0
Hamsters show a preference for Polycose, a mixture of starch-derived
glucose polymers, that is as strong as their preference for sucrose.
However, in the hamster, taste aversions to Polycose may be less easily
acquired than taste aversions to sucrose and the qualitative aspects of
Polycose are unknown in this species. In order to examine the taste of
Polycose in the hamster, we utilized a taste-aversion protocol with two
conditioning trials. Animals were trained to avoid one of three different
conditioning stimuli: 50 mM sucrose, 100 mM Polycose and a mixture of 50 mM
sucrose with 100 mM Polycose. Control animals were conditioned with
deionized water. After the second conditioning trial, generalization
testing began for the three conditioning stimuli plus 3 mM citric acid, 300
mM KCI and 30 mM NaCl. The results showed that aversions to Polycose,
sucrose or the Polycose/sucrose mixture cross- generalized, demonstrating
that Polycose and sucrose share a common taste percept in the hamster. None
of the aversions generalized to NaCl, citric acid or KCI. In addition,
comparisons among the patterns of taste generalizations indicated that the
tastes of Polycose and sucrose also had distinct qualitative components.
Finally, although the taste of 100 mM Polycose was more salient than the
taste of 50 mM sucrose, the taste of sucrose could still be detected in a
mixture with Polycose.
相似文献
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Purification of galectin-3 from ovine placenta: developmentally regulated expression and immunological relevance 总被引:1,自引:1,他引:1
Iglesias MM; Rabinovich GA; Ambrosio AL; Castagna LF; Sotomayor CE; Wolfenstein-Todel C 《Glycobiology》1998,8(1):59-65
Galectins, beta-galactoside-binding lectins, are extensively distributed in
the animal kingdom and share some basic molecular properties. Galectin-3, a
member of this family, is generally associated with differentiation,
morphogenesis, and metastasis. In this study, galectin-3 was isolated from
ovine placental cotyledons round the middle of the gestation period by
lactose extraction followed by affinity chromatography on lactosyl-agarose,
and separated from galectin-1 by size exclusion chromatography on a
Superose 12 column. Under native conditions this lectin behaved as a
monomer with an apparent molecular weight of approximately 29,000 and an
isoelectric point of 9.0. The partial amino acid sequence of the peptides
obtained by tryptic digestion of this protein followed by HPLC separation
showed striking homology with other members of the galectin-3 subfamily.
Furthermore, ovine placental galectin-3 exhibited specific mitogenic
activity toward rat spleen mononuclear cells. Besides, this protein
strongly reacted with a rabbit antiserum raised against a chicken galectin.
Results obtained by Western blot analysis showed that its expression was
greatly decreased in term placenta with respect to the middle of the
gestation period, suggesting a regulated expression throughout development.
相似文献
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Bayesian adaptive sequence alignment algorithms 总被引:2,自引:1,他引:2
The selection of a scoring matrix and gap penalty parameters continues to
be an important problem in sequence alignment. We describe here an
algorithm, the 'Bayes block aligner, which bypasses this requirement.
Instead of requiring a fixed set of parameter settings, this algorithm
returns the Bayesian posterior probability for the number of gaps and for
the scoring matrices in any series of interest. Furthermore, instead of
returning the single best alignment for the chosen parameter settings, this
algorithm returns the posterior distribution of all alignments considering
the full range of gapping and scoring matrices selected, weighing each in
proportion to its probability based on the data. We compared the Bayes
aligner with the popular Smith-Waterman algorithm with parameter settings
from the literature which had been optimized for the identification of
structural neighbors, and found that the Bayes aligner correctly identified
more structural neighbors. In a detailed examination of the alignment of a
pair of kinase and a pair of GTPase sequences, we illustrate the
algorithm's potential to identify subsequences that are conserved to
different degrees. In addition, this example shows that the Bayes aligner
returns an alignment-free assessment of the distance between a pair of
sequences.
相似文献
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