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131.
Rats carrying one copy of the fa allele are predisposed to diet-induced metabolic disturbances which contribute to hyperinsulinemia, obesity and dyslipidemia. To investigate the role of dietary carbohydrate and fat in the development of these conditions, we fed 6-week old male heterozygous (fa/+) lean rats carbohydrate-free diets containing primarily saturated fat either ad libitum or pair-fed. These diets were compared to standard chow and to a high saturated fat mixed diet containing 10% energy from sucrose for 4 weeks. The carbohydrate-free diet resulted in significantly lower circulating glucose levels compared to all other groups (p = 0.006). Weight gain was negligible in the carbohydrate free groups compared to standard diet and 10% sucrose diet (p = 0.03). This was reflected in energy efficiency which was markedly reduced (90%) in the carbohydrate-free groups compared to the other groups (p = 0.04). Corresponding changes were noted in fat pad mass. The subscapular and epididymal fat pads were increased 42% and 44%, respectively, in animals consuming the 10% sucrose diet compared to all other groups (p < 0.01). Comparable changes in fatty acid synthase (FAS) mRNA were observed in response to the carbohydrate-free diet, which resulted in a 53% decrease in adipocyte FAS mRNA (p < 0.001). Addition of 10% sucrose to the diet completely reversed this effect resulting in a 69% increase in adipocyte FAS mRNA compared to the carbohydrate-free groups (p = 0.01). Similarly, hepatic FAS mRNA was elevated by 51% and 66% in the 10% sucrose and standard diet groups respectively, compared to the carbohydrate-free groups. Therefore, diets that contain minimal carbohydrate may minimize net lipid storage and adiposity. 相似文献
132.
Solid-state spectral editing techniques have been used by others to simplify 13C CPMAS spectra of small organic molecules, synthetic organic polymers, and coals. One approach utilizes experiments such as cross-polarization-with-polarization-inversion and cross-polarization-with-depolarization to generate subspectra. This work shows that this particular methodology is also applicable to natural-abundance 13C CPMAS NMR studies of high-molecular-weight biopolymers. The editing experiments are demonstrated first with model peptides and then with -elastin, a high-molecular-weight peptidyl preparation obtained from the elastic fibers in mammalian tissue. The latter has a predominance of small, nonpolar residues, which is evident in the crowded aliphatic region of typical 13C CPMAS spectra. Spectral editing is particularly useful for simplifying the aliphatic region of the NMR spectrum of this elastin preparation. 相似文献
133.
Summary Skeletal muscle hypertrophy is promoted in vivo by administration of β-adrenergic receptor (βAR) agonists. Chicken skeletal
muscle cells were treated with 1 μM isoproterenol, a strong βAR agonist, between days 7 and 10 in culture. βAR population increased by approximately 40% during
this treatment; however, the ability of the cells to synthesize cyclic adenosine monophosphate (cAMP) was diminished by twofold.
Neither the basal concentration of cAMP nor the quantity of myosin heavy chain (MHC) was affected by the 3-d exposure to isoproterenol.
To understand further the relationship between intracellular cAMP levels, βAR population, and muscle protein accumulation,
intracellular cAMP levels were artificially elevated by treatment with 0–10 μM forskolin for 3 d. The basal concentration of cAMP in forskolintreated cells increased up to sevenfold in a dose-dependent
manner. Increasing concentrations of forskolin also led to an increase in βAR population, with a maximum increase of approximately
40–60% at 10 μM forskolin. A maximum increase of 40–50% in the quantity of MHC was observed at 0.2 μM forskolin, but higher concentrations of forskolin reduced the quanity of MHC back to control levels. At 0.2 μM forskolin, intracellular levels of cAMP were higher by approximately 35%, and the βAR population was higher by approximately
30%. Neither the number of muscle nuclei fused into myotubes nor the percentage of nuclei in myotubes was affected by forskolin
at any of the concentrations studied. 相似文献
134.
Computer-Aided Resolution of an Experimental Paradox in Bacterial Chemotaxis 总被引:1,自引:1,他引:0 下载免费PDF全文
Walid N. Abouhamad Dennis Bray Martin Schuster Kristin C. Boesch Ruth E. Silversmith Robert B. Bourret 《Journal of bacteriology》1998,180(15):3757-3764
Escherichia coli responds to its environment by means of a network of intracellular reactions which process signals from membrane-bound receptors and relay them to the flagellar motors. Although characterization of the reactions in the chemotaxis signaling pathway is sufficiently complete to construct computer simulations that predict the phenotypes of mutant strains with a high degree of accuracy, two previous experimental investigations of the activity remaining upon genetic deletion of multiple signaling components yielded several contradictory results (M. P. Conley, A. J. Wolfe, D. F. Blair, and H. C. Berg, J. Bacteriol. 171:5190–5193, 1989; J. D. Liu and J. S. Parkinson, Proc. Natl. Acad. Sci. USA 86:8703–8707, 1989). For example, “building up” the pathway by adding back CheA and CheY to a gutted strain lacking chemotaxis genes resulted in counterclockwise flagellar rotation whereas “breaking down” the pathway by deleting chemotaxis genes except cheA and cheY resulted in alternating episodes of clockwise and counterclockwise flagellar rotation. Our computer simulation predicts that trace amounts of CheZ expressed in the gutted strain could account for this difference. We tested this explanation experimentally by constructing a mutant containing a new deletion of the che genes that cannot express CheZ and verified that the behavior of strains built up from the new deletion does in fact conform to both the phenotypes observed for breakdown strains and computer-generated predictions. Our findings consolidate the present view of the chemotaxis signaling pathway and highlight the utility of molecularly based computer models in the analysis of complex biochemical networks. 相似文献
135.
136.
Diane T. Holland Kristin A. Godfredsen Theodore Page James D. Connor 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1998,707(1-2)
A simple reversed-phase high-performance liquid chromatography (HPLC) method for the simultaneous determination of caffeine and paraxanthine in human serum is described. Serum proteins are precipitated with perchloric acid and the resulting supernatant neutralized for direct injection onto an HPLC column. The method uses a phosphate–methanol mobile phase (85:15, v/v) at pH 4.9 with a flow-rate of 1.75 ml/min and quantitation is by UV absorbance at 274 nm. Elution times are approximately 18 min for caffeine and 8 min for paraxanthine. Theobromine and theophylline have elution times of 5.4 and 9.4 min and do not interfere in the assay. The intra-assay and between-assay means for precision and accuracy for both drugs are: 4.5% C.V. and 3.3% deviation. The sensitivity of the method is 50 ng/ml for each drug. 相似文献
137.
138.
Karl C. Desch Colin Kretz Andrew Yee Robert Gildersleeve Kristin Metzger Nidhi Agrawal Jane Cheng David Ginsburg 《PloS one》2015,10(4)
Von Willebrand factor (VWF) is a large, multimeric protein that regulates hemostasis by tethering platelets to the subendothelial matrix at sites of vascular damage. The procoagulant activity of plasma VWF correlates with the length of VWF multimers, which is proteolytically controlled by the metalloprotease ADAMTS13. To probe ADAMTS13 substrate specificity, we created phage display libraries containing randomly mutated residues of a minimal ADAMTS13 substrate fragment of VWF, termed VWF73. The libraries were screened for phage particles displaying VWF73 mutant peptides that were resistant to proteolysis by ADAMTS13. These peptides exhibited the greatest mutation frequency near the ADAMTS13 scissile residues. Kinetic assays using mutant and wild-type substrates demonstrated excellent agreement between rates of cleavage for mutant phage particles and the corresponding mutant peptides. Cleavage resistance of selected mutations was tested in vivo using hydrodynamic injection of corresponding full-length expression plasmids into VWF-deficient mice. These studies confirmed the resistance to cleavage resulting from select amino acid substitutions and uncovered evidence of alternate cleavage sites and recognition by other proteases in the circulation of ADAMTS13 deficient mice. Taken together, these studies demonstrate the key role of specific amino acids residues including P3-P2’ and P11’, for substrate specificity and emphasize the importance in flowing blood of other ADAMTS13–VWF exosite interactions outside of VWF73. 相似文献
139.
Kristin Palmqvist Lena Dahlman Fernando Valladares Anders Tehler Leopoldo G. Sancho Jan-Eric Mattsson 《Oecologia》2002,133(3):295-306
Aiming to investigate whether a carbon-to-nitrogen equilibrium model describes resource allocation in lichens, net photosynthesis (NP), respiration (R), concentrations of nitrogen (N), chlorophyll (Chl), chitin and ergosterol were investigated in 75 different lichen associations collected in Antarctica, Arctic Canada, boreal Sweden, and temperate/subtropical forests of Tenerife, South Africa and Japan. The lichens had various morphologies and represented seven photobiont and 41 mycobiont genera. Chl a, chitin and ergosterol were used as indirect markers of photobiont activity, fungal biomass and fungal respiration, respectively. The lichens were divided into three groups according to photobiont: (1) species with green algae, (2) species with cyanobacteria, and (3) tripartite species with green algal photobionts and cyanobacteria in cephalodia. Across species, thallus N concentration ranged from 1 to 50 mg g-1 dry wt., NP varied 50-fold, and R 10-fold. In average, green algal lichens had the lowest, cyanobacterial Nostoc lichens the highest and tripartite lichens intermediate N concentrations. All three markers increased with thallus N concentration, and lichens with the highest Chl a and N concentrations had the highest rates of both P and R. Chl a alone accounted for ca. 30% of variation in NP and R across species. On average, the photosynthetic efficiency quotient [KF=(NPmax+R)/R)] ranged from 2.4 to 8.6, being higher in fruticose green algal lichens than in foliose Nostoc lichens. The former group invested more N in Chl a and this trait increased NPmax while decreasing R. In general terms, the investigated lichens invested N resources such that their maximal C input capacity matched their respiratory C demand around a similar (positive) equilibrium across species. However, it is not clear how this apparent optimisation of resource use is regulated in these symbiotic organisms. 相似文献
140.
Kvissel AK Ramberg H Eide T Svindland A Skålhegg BS Taskén KA 《Cellular signalling》2007,19(2):401-409
Neuroendocrine (NE) cells may play a role in prostate cancer progression. Both androgen deprivation and cAMP are well known inducers of NE differentiation (NED) in the prostate. Gene-expression profiling of LNCaP cells, incubated in androgen stripped medium, showed that the Cbeta isoform of PKA is up-regulated during NE differentiation. Furthermore, by using semi-quantitative RT-PCR and immunoblotting analysis, we observed that the Cbeta splice variants are differentially regulated during this process. Whereas the Cbeta2 splice variant is down-regulated in growth arrested LNCaP cells, the Cbeta1, Cbeta3 and Cbeta4 variants, as well as the RIIbeta subunit of PKA, are induced in NE-like LNCaP cells. The opposite effect of Cbeta expression could be mimicked by androgen stimulation, implying the Cbeta gene of PKA as a putative new target gene for the androgen receptor in prostate cancer. Moreover, to investigate expression of PKA subunits during prostate cancer progression, we did immunoblotting of several prostatic cell lines and normal and tumor tissue from prostate cancer patients. Interestingly, multiple Cbeta subunits were also observed in human prostate specimens, and the Cbeta2 variant was up-regulated in tumor cells. In conclusion, it seems that the Cbeta isoforms play different roles in proliferation and differentiation and could therefore be potential markers for prostate cancer progression. 相似文献