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1.
Based on an idealized model of a homogeneous, isotropic beam-column, the second stiffest axis under static loading was derived. The maximum allowable force for the second stiffest axis was then examined. The ratio of the maximum allowable forces of the second stiffest axis to the stiffest axis was established. The stiffness ratio of the second stiffest axis to the stiffest axis was also found. Taking buckling into consideration, the safe load region for all possible acting directions was derived. The implications of the idealized model for cervical spine trauma are discussed. 相似文献
2.
3.
Patterson G. A.; Rock P.; Mitzner W. A.; Adkinson N. F. Jr; Sylvester J. T. 《Journal of applied physiology》1985,58(3):892-898
We determined the effects of extracorporeal perfusion with a constant flow (75 ml . min-1 . kg-1) of autologous blood on hemodynamics and fluid balance in sheep lungs isolated in situ. After 5 min, perfusate leukocyte and platelet counts fell by two-thirds. Pulmonary arterial pressure (Ppa) increased to a maximum of 32.0 +/- 3.4 Torr at 30 min and thereafter fell. Lung lymph flow (QL), measured from the superior thoracic duct, and perfusate thromboxane B2 (TXB2) concentrations followed similar time courses but lagged behind Ppa, reaching maxima of 4.1 +/- 1.2 ml/h and 2.22 +/- 0.02 ng/ml at 60 min. Lung weight gain, measured as the opposite of the weight change of the extracorporeal reservoir, and perfusate 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) concentration increased rapidly during the first 60 min and then more gradually. After 210 min, weight gain was 224 +/- 40 g and 6-keto-PGF1 alpha concentration, 4.99 +/- 0.01 ng/ml. The ratio of lymph to plasma oncotic pressure (pi L/pi P) at 30 min was 0.61 +/- 0.06 and did not change significantly. Imidazole (5 mM) reduced the changes in TXB2, Ppa, QL, and weight and platelet count but did not alter 6-keto-PGF1 alpha, pi L/pi P, or leukocyte count. Indomethacin (0.056 mM) reduced TXB2, 6-keto-PGF1 alpha, and the early increases in weight, Ppa, and QL but did not alter the time courses of leukocyte or platelet counts. Late in perfusion, however, Ppa and QL were greater than in either untreated or imidazole-treated lungs.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
4.
Spontaneous injury in isolated sheep lungs: role of perfusate leukocytes and platelets 总被引:1,自引:0,他引:1
Pearse D. B.; Brower R. G.; Adkinson N. F. Jr; Sylvester J. T. 《Journal of applied physiology》1989,66(3):1287-1296
Perfusion of isolated sheep lungs with blood causes spontaneous edema and hypertension preceded by decreases in perfusate concentrations of leukocytes (WBC) and platelets (PLT). To determine whether these decreases were caused by pulmonary sequestration, we continuously measured blood flow and collected pulmonary arterial and left atrial blood for cell concentration measurements in six lungs early in perfusion. Significant sequestration occurred in the lung, but not in the extracorporeal circuit. To determine the contribution of these cells to spontaneous injury in this model, lungs perfused in situ with a constant flow (100 ml.kg-1.min-1) of homologous leukopenic (WBC = 540 mm-3, n = 8) or thrombocytopenic blood (PLT = 10,000 mm-3, n = 6) were compared with control lungs perfused with untreated homologous blood (WBC = 5,320, PLT = 422,000, n = 8). Perfusion of control lungs caused a rapid fall in WBC and PLT followed by transient increases in pulmonary arterial pressure, lung lymph flow, and perfusate concentrations of 6-ketoprostaglandin F1 alpha and thromboxane B2. The negative value of reservoir weight (delta W) was measured as an index of fluid entry into the lung extravascular space during perfusion. delta W increased rapidly for 60 min and then more gradually to 242 g at 180 min. This was accompanied by a rise in the lymph-to-plasma oncotic pressure ratio (pi L/pi P). Relative to control, leukopenic perfusion decreased the ratio of wet weight to dry weight, the intra- plus extravascular blood weight, and the incidence of bloody lymph. Thrombocytopenic perfusion increased lung lymph flow and the rate of delta W, decreased pi L/pi P and perfusate thromboxane B2, and delayed the peak pulmonary arterial pressure. These results suggest that perfusate leukocytes sequestered in the lung and contributed to hemorrhage but were not necessary for hypertension and edema. Platelets were an important source of thromboxane but protected against edema by an unknown mechanism. 相似文献
5.
M Bohl G Schubert M Koch G Reck J Strecke M Wunderwald R Prousa K Ponsold 《Journal of steroid biochemistry》1987,26(5):589-597
The uterotropic activity of thirty 3-methoxyestradiol derivatives is measured and discussed on the basis of X-ray crystallographic results and quantitative structure-activity relationship analyses involving hydrophobic substituent constants pi and f as well as steric parameters Pr and L. In addition, estrogenicity is compared to data of interceptive activity and receptor binding affinity. All the biological data exhibit a high degree of intercorrelation. 17 beta-Hydroxysteroids having 14 alpha configuration reveal a generally better capability of high-affinity binding than those being 14 beta configurated. Between the uterotropic activity and the hydrophobicity of C14, C15 substituents, statistically significant correlations are found which suggest a close contact between the steroidal D-ring subsite and the receptor protein (e.g. for 14 alpha steroids: log UDD = -0.996 pi -0.392; n = 9, r = -0.943, s = 0.235, t = -7.5, alpha less than 0.001). The hydrophobic nature of both 14 alpha and 14 beta medium-sized substituents employed is shown by QSAR regressions to exert a stronger influence than steric effects. Furthermore, there are indications to additional hydrogen bonding and steric repulsion phenomena. As to the receptor-binding models discussed in the literature, it is concluded that the receptor protein has a high conformational flexibility to accommodate very different drug structures all having the common phenolic ring A. But, if an appropriate spacing of steroidal key atoms is recognized by the receptor and, consequently, the steroid-receptor complex is formed, the binding is complemented by hydrophobic interactions also in the D-ring region. 相似文献
6.
Pi-turns in proteins and peptides: Classification, conformation, occurrence, hydration and sequence. 总被引:1,自引:1,他引:0
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K. R. Rajashankar S. Ramakumar 《Protein science : a publication of the Protein Society》1996,5(5):932-946
The i + 5-->i hydrogen bonded turn conformation (pi-turn) with the fifth residue adopting alpha L conformation is frequently found at the C-terminus of helices in proteins and hence is speculated to be a "helix termination signal." An analysis of the occurrence of i + 5-->i hydrogen bonded turn conformation at any general position in proteins (not specifically at the helix C-terminus), using coordinates of 228 protein crystal structures determined by X-ray crystallography to better than 2.5 A resolution is reported in this paper. Of 486 detected pi-turn conformations, 367 have the (i + 4)th residue in alpha L conformation, generally occurring at the C-terminus of alpha-helices, consistent with previous observations. However, a significant number (111) of pi-turn conformations occur with (i + 4)th residue in alpha R conformation also, generally occurring in alpha-helices as distortions either at the terminii or at the middle, a novel finding. These two sets of pi-turn conformations are referred to by the names pi alpha L and pi alpha R-turns, respectively, depending upon whether the (i + 4)th residue adopts alpha L or alpha R conformations. Four pi-turns, named pi alpha L'-turns, were noticed to be mirror images of pi alpha L-turns, and four more pi-turns, which have the (i + 4)th residue in beta conformation and denoted as pi beta-turns, occur as a part of hairpin bend connecting twisted beta-strands. Consecutive pi-turns occur, but only with pi alpha R-turns. The preference for amino acid residues is different in pi alpha L and pi alpha R-turns. However, both show a preference for Pro after the C-termini. Hydrophilic residues are preferred at positions i + 1, i + 2, and i + 3 of pi alpha L-turns, whereas positions i and i + 5 prefer hydrophobic residues. Residue i + 4 in pi alpha L-turns is mainly Gly and less often Asn. Although pi alpha R-turns generally occur as distortions in helices, their amino acid preference is different from that of helices. Poor helix formers, such as His, Tyr, and Asn, also were found to be preferred for pi alpha R-turns, whereas good helix former Ala is not preferred. pi-Turns in peptides provide a picture of the pi-turn at atomic resolution. Only nine peptide-based pi-turns are reported so far, and all of them belong to pi alpha L-turn type with an achiral residue in position i + 4. The results are of importance for structure prediction, modeling, and de novo design of proteins. 相似文献
7.
Nourooz-Zadeh J Cooper MB Ziegler D Betteridge DJ 《Biochemical and biophysical research communications》2005,330(3):731-736
Although measurements of plasma F2-isoprostanes are established markers of oxidative stress, their quantification only reflects acute non-enzymatic lipid peroxidation. In this study, a new approach is described for the rapid isolation and measurement of urinary 8-epi-PGF2alpha and its endogenous beta-oxidation metabolites (2,3-dinor-8-epi-PGF2alpha and 2,3-dinor-5,6-dihydro-PGF2alpha) for use as index of total body oxidative stress. Isoprostanes were partitioned with ethyl acetate and subsequently purified by chromatography on an aminopropyl (NH2) and silica (Si) cartridge. Final analysis of F2-isoprostanes as trimethylsilyl-ester/pentafluorobenzyl ester derivatives was carried out by stable isotope dilution mass spectrometry. Overall recovery of F2-isoprostanes was 80+/-4%. Inter- and intra-assay coefficients of variation were 5% and 7%, respectively. In a group of healthy humans, the mean excretion rates expressed as nmol/mmol creatinine for 2,3-dinor-8-epi-PGF2alpha, 2,3-dinor-5,6-dihydro-8-epi-PGF2alpha, and 8-epi-PGF2alpha were 5.43+/-1.93, 2.16+/-0.71, and 0.36+/-0.16, respectively. Correlations were obtained between 8-epi-PGF2alpha and 2,3-dinor-8-epi-PGF2alpha or 2,3-dinor-5,6-dihydro-8-epi-PGF2alpha (r=0.998 and r=0.937, respectively). A strong relationship was also seen between 2,3-dinor-8-epi-PGF2 and 2,3-dinor-5,6-dihydro-8-epi-PGF2alpha (r=0.949). The new technique allows for high sample throughput and avoids the need for HPLC and/or other expensive equipment required for the initial sample preparation. Simultaneous analysis of urinary 8-epi-PGF2alpha and its metabolites should provide unique tool in clinical trials exploring the role of oxidant injury in human disease. 相似文献
8.
Biological growth and spread modeled by systems of recursions. I. Mathematical theory 总被引:2,自引:0,他引:2
R Lui 《Mathematical biosciences》1989,93(2):269-295
We study the asymptotic behavior of solutions to a system of recursions u in+1 = Qi[mu n], i = 1, ..., k. The vector operator Q has the origin theta and a positive vector beta as fixed points and is defined for vector-valued functions bounded between theta and gamma where gamma greater than or equal to beta. In addition, Q is order-preserving, commutes with translation, and is continuous in the topology of uniform convergence on compact subsets. Let theta less than or equal to pi much less than beta, and suppose that for all pi much less than alpha much less than beta, Q(n) alpha]----beta as n----infinity. If u0 much greater than pi on a sufficiently large ball and has bounded support, then un propagates with a speed c*(xi) in the direction of the unit vector xi as n----infinity. In certain cases, c*(xi) can be calculated explicitly. The results generalize those of a scalar equation studied by Weinberger. 相似文献
9.
Male lifespan extension with 17‐α estradiol is linked to a sex‐specific metabolomic response modulated by gonadal hormones in mice
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Michael Garratt Kim A. Lagerborg Yi‐Miau Tsai Andrzej Galecki Richard A. Miller 《Aging cell》2018,17(4)
Longevity in mammals is influenced by sex, and lifespan extension in response to anti‐aging interventions is often sex‐specific, although the mechanisms underlying these sexual dimorphisms are largely unknown. Treatment of mice with 17‐α estradiol (17aE2) results in sex‐specific lifespan extension, with an increase in median survival in males of 19% and no survival effect in females. Given the links between lifespan extension and metabolism, we performed untargeted metabolomics analysis of liver, skeletal muscle and plasma from male and female mice treated with 17aE2 for eight months. We find that 17aE2 generates distinct sex‐specific changes in the metabolomic profile of liver and plasma. In males, 17aE2 treatment raised the abundance of several amino acids in the liver, and this was further associated with elevations in metabolites involved in urea cycling, suggesting altered amino acid metabolism. In females, amino acids and urea cycling metabolites were unaffected by 17aE2. 17aE2 also results in male‐specific elevations in a second estrogenic steroid—estriol‐3‐sulfate—suggesting different metabolism of this drug in males and females. To understand the underlying endocrine causes for these sexual dimorphisms, we castrated males and ovariectomized females prior to 17aE2 treatment, and found that virtually all the male‐specific metabolite responses to 17aE2 are inhibited or reduced by male castration. These results suggest novel metabolic pathways linked to male‐specific lifespan extension and show that the male‐specific metabolomic response to 17aE2 depends on the production of testicular hormones in adult life. 相似文献
10.
A Oguogho G Karanikas H Kritz G Riehs O Wagner H Sinzinger 《Prostaglandins, leukotrienes, and essential fatty acids》1999,60(2):129-134
Isoprostanes are a new family of compounds generated by the free radical catalyzed action on arachidonic acid. Formed during oxidation they have been claimed to be a reliable indicator of in vivo oxidation injury. We assessed the amount of 8-epi-PGF2alpha in human surgical specimens as compared to PGI2 (via its stable metabolite 6-oxo-PGF1alpha), the major compound generated by vascular tissue. 8-epi-PGF2alpha is low in normal vascular tissue as is the 8-epi-PGF2alpha/6-oxo-PGF1alpha ratio. The vessels of smokers in general exhibited an increased 8-epi-PGF2alpha (r=0.82) and a decreased 6-oxo-PGF1alpha (r=0.71). The 8-epi-PGF2alpha/6-oxo-PGF1alpha ratio is, not significantly, increased in vessels derived from hyperlipidemics and hypertensives. These findings indicate that lipid peroxidation occurs within the human arterial wall as evidenced by 8-epi-PGF2alpha, probably further decreasing the synthesis of PGI2 and promoting atherogenic mechanisms. 相似文献
11.
Theoretical CD studies of polypeptide helices: examination of important electronic and geometric factors 总被引:4,自引:0,他引:4
An improved model for calculating the CD of polypeptides has been developed. Excited state wavefunctions were derived from CNDO/S (complete neglect of differential overlap, spectroscopic) calculations on N-methylacetamide. Four discrete peptide-localized transitions were employed: pi 0 pi* (NV1), pi* + pi* (NV2), n pi*, and n' pi*. Inclusion of the pi + pi transition (lambda 0 = 140 nm) significantly improves the accuracy of the calculated CD spectra in the 180-250-nm region. Spectra were computed for various helical structures, including right-handed alpha-, alpha II-, omega-, pi-, 3(10-), and poly (proline) I-helices, and the left-handed poly (proline) II-helix. Sensitivity to changes in the peptide backbone geometry and chain length are examined. Electronic factors such as ground-state charge distribution, hybridization effects, and basis set deorthogonalization have been investigated. The nonconservative nature of the poly (Pro) I and II CD spectra is reproduced, and the helix band present in earlier exciton calculations on the alpha-helix has been diminished. 相似文献
12.
We compare the conformational distributions of Ace-Ala-Nme and Ace-Gly-Nme sampled in long simulations with several molecular mechanics (MM) force fields and with a fast combined quantum mechanics/molecular mechanics (QM/MM) force field, in which the solute's intramolecular energy and forces are calculated with the self-consistent charge density functional tight binding method (SCCDFTB), and the solvent is represented by either one of the well-known SPC and TIP3P models. All MM force fields give two main states for Ace-Ala-Nme, beta and alpha separated by free energy barriers, but the ratio in which these are sampled varies by a factor of 30, from a high in favor of beta of 6 to a low of 1/5. The frequency of transitions between states is particularly low with the amber and charmm force fields, for which the distributions are noticeably narrower, and the energy barriers between states higher. The lower of the two barriers lies between alpha and beta at values of psi near 0 for all MM simulations except for charmm22. The results of the QM/MM simulations vary less with the choice of MM force field; the ratio beta/alpha varies between 1.5 and 2.2, the easy pass lies at psi near 0, and transitions between states are more frequent than for amber and charmm, but less frequent than for cedar. For Ace-Gly-Nme, all force fields locate a diffuse stable region around phi = pi and psi = pi, whereas the amber force field gives two additional densely sampled states near phi = +/-100 degrees and psi = 0, which are also found with the QM/MM force field. For both solutes, the distribution from the QM/MM simulation shows greater similarity with the distribution in high-resolution protein structures than is the case for any of the MM simulations. 相似文献
13.
The fluorescence spectra of 6-propionyl-2-(dimethylamino)naphthalene (Prodan) and 6-dodecanoyl-2-(dimethylamino)naphthalene (Laurdan) in bilayer membranes of 1,2-distearoylphosphatidylcholine (DSPC) were observed as a function of pressure at constant temperature. The emission spectra of Prodan and Laurdan varied with the pressure-induced states of bilayer membranes. The maximum emission wavelength (lambda(max)) of Prodan characteristic of the liquid crystalline (L(alpha)), lamellar gel (L(beta)') and pressure-induced interdigitated gel (L(beta)I) phases of the DSPC bilayer was 480, 440 and 500 nm, respectively. On the other hand, the lambda(max) of Laurdan characteristic of the L(alpha) and L(beta)' phases was 480 and 440 nm in a similar manner as Prodan probe. However, no change in the lambda(max) was observed in spite of the occurrence of the interdigitation of bilayer. Since the lambda(max) reflects the solvent property around the probe molecules, we could speculate about the location of fluorescent probe in the bilayer membranes. In the L(alpha) phase the same chromophore group of Prodan and Laurdan probes distributes around phosphate group of lipid (i.e., polar region). The transformation of bilayer into the L(beta)' phase causes the Prodan and Laurdan molecules to move into the glycerol backbone (i.e., less polar) region. In the ripple gel (P(beta)') phase, the emission spectrum of Prodan shows a broad peak at about 480 nm and a shoulder around 440 nm, which means that the Prodan molecules are widespread over the wide range from the glycerol backbone to the hydrophilic part of bilayer. The P(beta)'/L(beta)I phase transition causes the Prodan molecule to squeeze out from the glycerol backbone region and to move the hydrophilic region near the bilayer surface. Contrarily, the Laurdan molecule was not squeezed out from the glycerol backbone region because the long acyl chain of Laurdan serves as an anchor in the hydrophobic core of bilayer. The ratio of fluorescence intensity of Prodan at 480 nm to that at 440 nm, F(480)/F(440), is available to observation of bilayer phase transitions. The plot of F(480)/F(440) versus pressure seems to be useful for the recognition of bilayer phase transition, especially the bilayer interdigitation. 相似文献
14.
It is shown that ATP dissociates very slowly (koff less than 6.4 x 10(5) s-1, t1/2 greater than 3 h) from the three noncatalytic sites of E. coli F1-ATPase and that ADP dissociates from these three sites in a homogeneous fashion with koff = 1.5 x 10(-4) s-1 (t1/2 = 1.35 h). Mutagenesis of alpha-subunit residues R171 and Q172 in the 'glycine-rich loop' (Homology A) consensus region of the noncatalytic sites was carried out to test the hypothesis that unusually bulky residues at these positions are responsible wholly or partly for the observed tight binding of adenine nucleotides. The mutations alpha Q172G or alpha R171S,Q172G had no effects on ATP or ADP binding to or rates of dissociation from F1 noncatalytic sites. KdATP and KdADP of isolated alpha-subunit were weakened by approximately 1 order of magnitude in both mutants. The results suggest that neither residue alpha R171 nor alpha Q172 interacts directly with bound nucleotide, and show that the presence of bulky residues per se in the glycine-rich loop region of F1-alpha-subunit is not responsible for tight binding in the noncatalytic sites. 相似文献
15.
Ohgi K Kudo S Takeuchi M Iwama M Irie M 《Bioscience, biotechnology, and biochemistry》2000,64(10):2068-2074
To investigate the role of Phe101, a component of a base recognition site (B2 site) of a base-nonspecific RNase Rh from Rhizopus niveus, we prepared several enzymes mutated at this position, F101W, F101L, F101I, F101A, F101Q, F101R, and F101K, and their enzymatic activities towards RNA, 16 dinucleoside phosphates, and 2', 3'-cyclic pyrimidine nucleotides were measured. Enzymatic activity toward RNA of F101W, F101L, and F101I were about 7, 20, and 3.8% of the native enzyme, respectively, and those of the other mutants were less than 1% of the RNase Rh. Similar results were also obtained with GpG as substrate. Thus, it was concluded that Phe101 is a very important residue as a component of the B2 site of RNase Rh, and its role could be replaced by Leu, then Trp and Ile, though in less effectively. The results suggested that some kind of interaction between B2 base and the side chain of amino acid residue at the 101th position, such as pi/pi or CH/pi interaction is very important for the enzymatic activity of RNase Rh. The mutation of Phe101 markedly affected the enzymatic activity toward dinucleoside phosphates and polymer substrates, but only moderately the rate of hydrolysis of cyclic nucleotides, indicating the presence of secondary effect of the mutation on B1 site. 相似文献
16.
We present a quantitative kinetic model for the transient velocity (microM of cGMP hydrolyzed/s) response of retinal rod outer segment (ROS) cGMP phosphodiesterase (v(t) versus t) to a stimulating light pulse in the linear response range. The model gives an excellent fit to experimental v(t) versus t data for ROS suspensions at different concentrations of GTP and GDP and clarifies experimental results which are difficult to understand in the absence of such a model. It contains the minimum number of steps required to fit our experimental data and consists of one rate-limiting step with specific rate kL for the production of active phosphodiesterase (PDE), PDE*, by photoactivated rhodopsin, R*, and deactivation processes for R* and PDE* with lifetimes tau R and tau P, respectively. The experimental graphs of v(t) versus t at each concentration of GTP and GDP are characterized by a fast rise to a peak value, vpeak, followed by a slow decay to zero level. The minimal kinetic model allows us to characterized completely the effects of GTP and GDP, and any other pertinent species, in terms of their effects on the parameters kL, tau R, and tau P. Our kinetic model indicates that for "washed" ROS preparations (a) the risetime of v(t) is determined by tau P which has a value of about 2 s and is insensitive to [GTP]. (b) The decay of v(t) is determined by tau R which decreases with [GTP] and has a value greater than 300 s at low [GTP] and a limiting value of 50 s at high [GTP]. We attribute the greater than 300 s lifetime to the complex R*G (where G is ROS G protein) and the 50-s lifetime to free R*. (c) The rate kL increases hyperbolically with [GTP] with a half-maximal value of 56 microM and kL.max = 22-45 s-1. (d) Peak velocity is given by the expression vpeak alpha kL tau P which is consistent with the dependence of kL on [GTP] and the experimental finding that vpeak varies hyperbolically with [GTP]. The minimal model has also allowed us to (a) develop clear definitions of amplification for the light-triggered enzymatic cascade and (b) clarify experimental methods for measuring gain.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
17.
The core domain of chemokines binds CCR5 extracellular domains while their amino terminus interacts with the transmembrane helix bundle 总被引:14,自引:0,他引:14
Blanpain C Doranz BJ Bondue A Govaerts C De Leener A Vassart G Doms RW Proudfoot A Parmentier M 《The Journal of biological chemistry》2003,278(7):5179-5187
CCR5 is a functional receptor for various inflammatory CC-chemokines, including macrophage inflammatory protein (MIP)-1alpha and RANTES (regulated on activation normal T cell expressed and secreted), and is the main coreceptor of human immunodeficiency viruses. The second extracellular loop and amino-terminal domain of CCR5 are critical for chemokine binding, whereas the transmembrane helix bundle is involved in receptor activation. Chemokine domains and residues important for CCR5 binding and/or activation have also been identified. However, the precise way by which chemokines interact with and activate CCR5 is presently unknown. In this study, we have compared the binding and functional properties of chemokine variants onto wild-type CCR5 and CCR5 point mutants. Several mutations in CCR5 extracellular domains (E172A, R168A, K191A, and D276A) strongly affected MIP-1alpha binding but had little effect on RANTES binding. However, a MIP/RANTES chimera, containing the MIP-1alpha N terminus and the RANTES core, bound to these mutants with an affinity similar to that of RANTES. Several CCR5 mutants affecting transmembrane helices 2 and 3 (L104F, L104F/F109H/F112Y, F85L/L104F) reduced the potency of MIP-1alpha by 10-100 fold with little effect on activation by RANTES. However, the MIP/RANTES chimera activated these mutants with a potency similar to that of MIP-1alpha. In contrast, LD78beta, a natural MIP-1alpha variant, which, like RANTES, contains a proline at position 2, activated these mutants as well as RANTES. Altogether, these results suggest that the core domains of MIP-1alpha and RANTES bind distinct residues in CCR5 extracellular domains, whereas the N terminus of chemokines mediates receptor activation by interacting with the transmembrane helix bundle. 相似文献
18.
The static elastic properties of 45 human thoracic and 20 abdominal aortas in vitro and the parameters of a new model 总被引:11,自引:0,他引:11
Segments of 45 human thoracic and 20 abdominal aortas, including 13 pairs, aged 30-88 yr at autopsy, were perfused with 37 degrees C Tyrode's solution at in-situ length. Diameter changes due to 20 mmHg pressure steps, between 20 and 180 mmHg, were measured to 1 micron accuracy with balanced transducers. Absolute diameter at 100 mmHg was measured to 50 micron accuracy. At 100 mmHg, cross-sectional area ranged from 2.6 to 7.6 for thoracic and from 1.0 to 3.2 cm2 for abdominal segments. Compliances ranged from 1.9 to 17 for thoracic and from 0.6 to 4.4 mm3/mmHg.cm for abdominal segments. An arctangent model with three free parameters A(p) = Am(1/2 + tan-1 [p-p0)/p1)/pi) explained over 99% of the variance in area with pressure for each aorta. Changes in compliance, characteristic impedance and propagation velocity are equally well described. Abdominal fits on the average appeared down scaled by a factor of 2 and shifted 20 mmHg towards lower pressures from paired thoracic (significant at p = 0.001). 相似文献
19.
The 24-hours urinary excretion of immunoreactive prostaglandin F2 alpha (U-iPGF2 alpha) in normal children on a free diet was not significantly different in 30 boys (aged 3-15 years; geometric mean 589 ng/24 h) compared to 27 girls (aged 4-14 years; mean 473 ng/24 h). In both sexes this excretion rose with age until adolescence where it reached a plateau. In normal adults the men had significantly higher (p less than 0.001) excretions of U-iPGF2 alpha than the women; also body weight and urinary creatinine excretion were higher in men (p less than 0.001). In the children, as well as in the total population, U-iPGF2 alpha correlated best with body weight (r = 0.44 and r = 0.48 respectively; p less than 0.001) and the urinary creatinine excretion (r = 0.53 and 0.57 respectively; p less than 0.001); both body weight and urinary creatinine excretion are reflections of total body development. After the correction for urinary creatinine excretion or for body weight, the sex difference in the adult U-iPGF2 alpha totally disappeared. 相似文献
20.
Torsion elastic constants obtained from fluorescence polarization anisotropy (FPA) measurements on fifty-three 24 and 27 base-pair (bp) DNAs were recently reported [F. Pedone, F. Mazzei, D. Santoni, Sequence-dependent DNA torsional rigidity: a tetranucleotide code, Biophys. Chem. 112 (2004) 77-88; F. Pedone, F. Mazzei, M. Matzeu, F. Barone, Torsional constant of 27-mer DNA oligomers of different sequences, Biophys. Chem. 94 (2001) 175-184]. The problem of extracting reliable torsion elastic constants (alpha) from FPA measurements on such short DNAs is examined in detail. The difficulty is illustrated by two (fictitious) 24 bp DNAs with approximately 5-fold different torsion elastic constants and 10% different initial anisotropies (r(0)), which exhibit practically indistinguishable anisotropy decays for all t>1 ns. FPA data were simulated for 24 bp DNAs with different input values of alpha and r(0) in the presence and absence of Poisson noise, and were fitted using different choices of the adjustable and fixed parameters. Experimental data for a 24 bp DNA were fitted in a similar manner. For either the simulated or experimental FPA data, it was not possible to determine both the initial anisotropy, r(0), and the torsion elastic constant, alpha, in a reliable (i.e. statistically significant) manner in the presence of Poisson noise. When r(0) is assumed to be fixed at any particular value in the fitting protocol, a unique best-fit value of alpha is obtained, but that best-fit alpha is extremely sensitive to small deviations of the assumed fixed value of r(0) away from the input r(0)-value of the simulated data. Pedone et al. fitted their FPA data by assuming that r(0)=0.360, and adjusting alpha, the hydrodynamic radius (R(H)), and effective length (L). In fact, the reported best-fit values of R(H) and L lay significantly outside their expected ranges. When this same fitting protocol is applied to simulated data for 27 bp DNAs, better overall agreement with the reported experimental values (alpha, R(H), and L) is obtained for a model, wherein all DNAs have the same typical input alpha=5.9 x 10(-12) dyn cm, R(H)=10.0 A, and L=27 (3.4)+2.7=94.5 A, but a 1.00- to 1.13-fold range of r(0)-values, than for the model of Pedone et al., wherein all DNAs have the same input r(0)=0.360, R(H)=10.0 A, and L=94.5 A, but a approximately 3-fold range of alpha-values. It is concluded that, in the absence of reliable independent estimates of r(0) for every DNA, the alpha-values reported for 24 and 27 bp DNAs cannot be regarded as experimentally justified. The reliability of the torsion elastic constants reported for the 136 distinct tetranucleotide steps, which are inferred from the values reported for the fifty-three 24 and 27 bp DNAs, is also briefly discussed. 相似文献