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151.
Balancing forces: architectural control of mechanotransduction 总被引:1,自引:0,他引:1
All cells exist within the context of a three-dimensional microenvironment in which they are exposed to mechanical and physical cues. These cues can be disrupted through perturbations to mechanotransduction, from the nanoscale-level to the tissue-level, which compromises tensional homeostasis to promote pathologies such as cardiovascular disease and cancer. The mechanisms of such perturbations suggest that a complex interplay exists between the extracellular microenvironment and cellular function. Furthermore, sustained disruptions in tensional homeostasis can be caused by alterations in the extracellular matrix, allowing it to serve as a mechanically based memory-storage device that can perpetuate a disease or restore normal tissue behaviour. 相似文献
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153.
The basic equations for the elementary step in the diffusion–collision–coalescence model of protein folding are derived for the case of two radially diffusing spherical microdomains. Refinements and biological implications of the mechanism are considered; included are detailed discussions of the parameters of the model, the possibilities of rotational diffusion and surface diffusion in one or two dimensions, the nature of the microdomains, and the application of the model to protein unfolding. 相似文献
154.
155.
Weaver J Porasuphatana S Tsai P Budzichowski T Rosen GM 《Free radical research》2005,39(10):1027-1033
The free radical, nitric oxide ( radicalNO), is responsible for a myriad of physiological functions. The ability to verify and study radicalNO in vivo is required to provide insight into the events taking place upon its generation and in particular the flux of radicalNO at relevant cellular sites. With this in mind, several iron-chelates (Fe2+(L)2) have been developed, which have provided a useful tool for the study and identification of radicalNO through spin-trapping and electron paramagnetic resonance (EPR) spectroscopy. However, the effectiveness of radicalNO detection is dependent on the Fe2+(L)2 complex. The development of more efficient and stable Fe2+(L)2 chelates may help to better understand the role of radicalNO in vivo. In this paper, we present data comparing several proline derived iron-dithiocarbamate complexes with the more commonly used spin traps for radicalNO, Fe2+-di(N-methyl-D-glutamine-dithiocarbamate) (Fe2+(MGD)2) and Fe2+-di(N-(dithiocarboxy)sarcosine) (Fe2+(DTCS)2). We evaluate the apparent rate constant (kapp) for the reaction of radicalNO with these Fe2+(L)2complexes and the stability of the corresponding Fe2+(NO)(L)2 in presence of NOS I. 相似文献
156.
Huang J Shi J Molle V Sohlberg B Weaver D Bibb MJ Karoonuthaisiri N Lih CJ Kao CM Buttner MJ Cohen SN 《Molecular microbiology》2005,58(5):1276-1287
A complex programme of regulation governs gene expression during development of the morphologically and biochemically complex eubacterial genus Streptomyces. Earlier work has suggested a model in which 'higher level' pleiotropic regulators activate 'pathway-specific' regulators located within chromosomal gene clusters encoding biosynthesis of individual antibiotics. We used mutational analysis and adventitious overexpression of key Streptomyces coelicolor regulators to investigate functional interactions among them. We report here that cluster-situated regulators (CSRs) thought to be pathway-specific can also control other antibiotic biosynthetic gene clusters, and thus have pleiotropic actions. Surprisingly, we also find that CSRs exhibit growth-phase-dependent control over afsR2/afsS, a 'higher level' pleiotropic regulatory locus not located within any of the chromosomal gene clusters it targets, and further demonstrate that cross-regulation by CSRs is modulated globally and differentially during the S. coelicolor growth cycle by the RNaseIII homologue AbsB. Our results, which reveal a network of functional interactions among regulators that govern production of antibiotics and other secondary metabolites in S. coelicolor, suggest that revision of the currently prevalent view of higher-level versus pathway-specific regulation of secondary metabolism in Streptomyces species is warranted. 相似文献
157.
Weaver AM 《Developmental cell》2005,9(1):35-38
Cell motility depends on the conversion of extracellular cues into intracellular cytoskeletal responses. A recent Keystone meeting on cell migration and adhesion showcased advances in the field. 相似文献
158.
Analysis of protein expression during oxidative stress in breast epithelial cells using a stable isotope labeled proteome internal standard 总被引:1,自引:0,他引:1
Normal cells undergo a variety of molecular and physiological changes upon malignant transformation, including their responses to environmental factors that induce oxidative stress. Understanding the molecular pathways regulating these changes would facilitate the development of novel cancer treatments and chemoprevention strategies. Differences in the oxidative stress response were investigated between nonmalignant (S-1) and malignant (T4-2) cell lines (both derived from the HMT-3522 breast epithelial cells) using proteomic approaches. A modification of the stable isotope labeling of amino acids in cell culture (SILAC) approach was employed in which a [(13)C,(15)N]-labeled proteome was prepared from both cells. Relative quantification of the proteome derived from the S-1 cells and the T4-2 cells was then conducted using a [(13)C,(15)N]-labeled proteome as the internal standard. Differentially expressed proteins that changed in a similar manner in both cell lines were mainly stress response proteins, including heat shock proteins, peroxiredoxins, and redox proteins. Proteins that showed significant change in expression level in only one the cell lines included cytoskeleton proteins and proteins implicated in cell cycle and apoptosis regulation. Fortilin was found to be significantly up regulated in the transformed T4-2 cells after H(2)O(2) treatment but not in the parental S-1 cells. However, Ran/TC4 was up regulated by H(2)O(2) in the nonmalignant breast epithelial cells but not in the malignant cells. These results suggest that the malignant T4-2 cells have acquired more resistance to H(2)O(2)-induced apoptosis than the nonmalignant S-1 cells. 相似文献
159.
Zhao Y Martin BR Wastney ME Schollum L Weaver CM 《Experimental biology and medicine (Maywood, N.J.)》2005,230(8):536-542
The acute and chronic effects of whey proteins on calcium metabolism and bone were evaluated. In acute studies, 8-week-old male rats were gavaged with 50 mg whey protein concentrate (WPC) and 25 mg calcium. 45Ca was administered intravenously or orally. Kinetic studies were performed, and femurs were harvested. Four of seven WPCs significantly increased femur uptake of 45Ca compared with controls. One WPC at 50 mg enhanced calcium absorption over a range of calcium intakes from 35.1 +/- 9.4% to 42.4 +/- 14.0% (P < 0.01). Three of the most effective WPCs were tested further in a chronic feeding study. One hundred 3-week-old rats were randomly divided into four adequate dietary calcium (ADC; 0.4% Ca) groups (control of 20% casein and three WPC groups with 1% substitution of casein with each of three WPCs) and two low calcium (LC; 0.2% Ca) groups (control of 20% casein and one WPC group with 1% substitution of casein with one WPC). After 8 weeks, there was no effect of WPCs on femur uptake of 45Ca among ADC groups and there was no effect of WPCs on calcium retention, femur breaking force, femur bone mineral density, or total femur calcium at either dietary calcium intake. However, whole body bone mineral content (BMC) was significantly higher (P < 0.05) in the three whey protein concentrate ADC groups compared with the ADC control group. Total BMC at the proximal tibia in whey protein ADC groups was increased, as shown by peripheral quantitative computed tomography. Our results indicate that the acute calcium absorption-enhancing effect of whey proteins did not persist through long-term feeding in rats. However, the initial enhancement of calcium absorption by whey protein was sufficient to increase BMC. 相似文献
160.
Owegi MA Carenbauer AL Wick NM Brown JF Terhune KL Bilbo SA Weaver RS Shircliff R Newcomb N Parra-Belky KJ 《The Journal of biological chemistry》2005,280(18):18393-18402
Subunit E is a component of the peripheral stalk(s) that couples membrane and peripheral subunits of the V-ATPase complex. In order to elucidate the function of subunit E, site-directed mutations were performed at the amino terminus and carboxyl terminus. Except for S78A and D233A/T202A, which exhibited V(1)V(o) assembly defects, the function of subunit E was resistant to mutations. Most mutations complemented the growth phenotype of vma4Delta mutants, including T6A and D233A, which only had 25% of the wild-type ATPase activity. Residues Ser-78 and Thr-202 were essential for V(1)V(o) assembly and function. The mutation S78A destabilized subunit E and prevented assembly of V(1) subunits at the membranes. Mutant T202A membranes exhibited 2-fold increased V(max) and about 2-fold less of V(1)V(o) assembly; the mutation increased the specific activity of V(1)V(o) by enhancing the k(cat) of the enzyme 4-fold. Reduced levels of V(1)V(o) and V(o) complexes at T202A membranes suggest that the balance between V(1)V(o) and V(o) was not perturbed; instead, cells adjusted the amount of assembled V-ATPase complexes in order to compensate for the enhanced activity. These results indicated communication between subunit E and the catalytic sites at the A(3)B(3) hexamer and suggest potential regulatory roles for the carboxyl end of subunit E. At the carboxyl end, alanine substitution of Asp-233 significantly reduced ATP hydrolysis, although the truncation 229-233Delta and the point mutation K230A did not affect assembly and activity. The implication of these results for the topology and functions of subunit E within the V-ATPase complex are discussed. 相似文献