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991.
Kapustina M Weinreb GE Costigliola N Rajfur Z Jacobson K Elston TC 《Biophysical journal》2008,94(12):4605-4620
Actomyosin-based cortical contractility is a common feature of eukaryotic cells and is involved in cell motility, cell division, and apoptosis. In nonmuscle cells, oscillations in contractility are induced by microtubule depolymerization during cell spreading. We developed an ordinary differential equation model to describe this behavior. The computational model includes 36 parameters. The values for all but two of the model parameters were taken from experimental measurements found in the literature. Using these values, we demonstrate that the model generates oscillatory behavior consistent with current experimental observations. The rhythmic behavior occurs because of the antagonistic effects of calcium-induced contractility and stretch-activated calcium channels. The model makes several experimentally testable predictions: 1), buffering intracellular calcium increases the period and decreases the amplitude of cortical oscillations; 2), increasing the number or activity of stretch activated channels leads to an increase in period and amplitude of cortical oscillations; 3), inhibiting Ca2+ pump activity increases the period and amplitude of oscillations; and 4), a threshold exists for the calcium concentration below which oscillations cease. 相似文献
992.
Lin X Gudgeon NH Hui EP Jia H Qun X Taylor GS Barnardo MC Lin CK Rickinson AB Chan AT 《Cancer immunology, immunotherapy : CII》2008,57(7):963-975
Nasopharyngeal carcinoma (NPC), an Epstein–Barr virus (EBV)-associated tumour common in Southern Chinese populations, is a
potentially important target for T cell-based immunotherapy. The tumour cells are HLA class I- and II-positive and express
a limited subset of EBV latent proteins, namely the nuclear antigen EBNA1 and the latent membrane proteins LMP2 and (in some
cases) LMP1. To ask whether the tumour develops in the presence of a potentially protective host response or in its absence,
we set out to determine the prevailing levels of CD4+ and CD8+ T cell memory to these proteins in NPC patients at tumour diagnosis.
We first screened healthy Chinese donors against Chinese strain EBNA1, LMP1 and LMP2 sequences in Elispot assays of interferon-γ
release and identified the immunodominant CD4+ and CD8+ epitope peptides presented by common Chinese HLA alleles. Then, comparing
60 patients with >70 healthy controls on peptide epitope mini-panels, we found that T cell memory to CD4 epitopes in all three
proteins was unimpaired in the blood of patients at diagnosis. In most cases NPC patients also showed detectable responses
to CD8 epitopes relevant to their HLA type, the one consistent exception being the absence in patients of a B*4001-restricted
response to LMP2. We infer that NPC arises in patients whose prevailing levels of T cell memory to tumour-associated EBV proteins
is largely intact; the therapeutic goal must therefore be to re-direct the existing memory repertoire more effectively against
antigen-expressing tumour cells.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
993.
Pendergrass KD Pirro NT Westwood BM Ferrario CM Brosnihan KB Chappell MC 《American journal of physiology. Heart and circulatory physiology》2008,295(1):H10-H20
Sex differences in blood pressure are evident in experimental models and human subjects, yet the mechanisms underlying this disparity remain equivocal. The current study sought to define the extent of male-female differences in the circulating and tissue renin-angiotensin aldosterone systems (RAASs) of congenic mRen(2). Lewis and control Lewis rats. Male congenics exhibited higher systolic blood pressure than females [200 +/- 4 vs. 146 +/- 7 mmHg, P < 0.01] or Lewis males and females [113 +/- 2 vs. 112 +/- 2 mmHg, P > 0.05]. Plasma ANG II levels were twofold higher in male congenics [47 +/- 3 vs. 19 +/- 3 pM, P < 0.01] and fivefold higher than in male or female Lewis rats [6 +/- 1 vs. 6 +/- 1 pM]. ANG I levels were also highest in the males; however, plasma ANG-(1-7) was higher in female congenics. Male congenics exhibited greater circulating renin and angiotensin-converting enzyme (ACE) activities, as well as angiotensinogen, than female littermates. Renal cortical and medullary ANG II levels were also higher in the male congenics versus all the other groups; ANG I was lower in the males. Cortical ACE2 activity was higher in male congenics, yet neprilysin activity and protein were greater in the females, which may contribute to reduced renal levels of ANG II. These data reveal that sex differences in both the circulating and renal RAAS are apparent primarily in the hypertensive group. The enhanced activity of the RAAS in male congenics may contribute to the higher pressure and tissue injury evident in the strain. 相似文献
994.
995.
Allahdadi KJ Duling LC Walker BR Kanagy NL 《American journal of physiology. Heart and circulatory physiology》2008,294(2):H920-H927
We reported previously that simulating sleep apnea by exposing rats to eucapnic intermittent hypoxia (E-IH) causes endothelin-dependent hypertension and increases constrictor sensitivity to endothelin-1 (ET-1). In addition, augmented ET-1-induced constriction in small mesenteric arteries (sMA) is mediated by increased Ca(2+) sensitization independent of Rho-associated kinase. We hypothesized that exposing rats to E-IH augments ET-1-mediated vasoconstriction by increasing protein kinase C (PKC)-dependent Ca(2+) sensitization. In sMA, the nonselective PKC inhibitor GF-109203x (3 microM) significantly inhibited ET-1-stimulated constriction in E-IH arteries but did not affect ET-1-stimulated constriction in sham arteries. Phospholipase C inhibitor U-73122 (1 microM) also inhibited constriction by ET-1 in E-IH but not sham sMA. In contrast, the classical PKC (cPKC) inhibitor G?-6976 (1 microM) had no effect on ET-1-mediated vasoconstriction in either group, but a PKCdelta-selective inhibitor (rottlerin, 3 microM) significantly decreased ET-1-mediated constriction in E-IH but not in sham sMA. ET-1 increased PKCdelta phosphorylation in E-IH but not sham sMA. In contrast, ET-1 constriction in thoracic aorta from both sham and E-IH rats was inhibited by G?-6976 but not by rottlerin. These observations support our hypothesis that E-IH exposure significantly increases ET-1-mediated constriction of sMA through PKCdelta activation and modestly augments ET-1 contraction in thoracic aorta through activation of one or more cPKC isoforms. Therefore, upregulation of a PKC pathway may contribute to elevated ET-1-dependent vascular resistance in this model of hypertension. 相似文献
996.
Pasternak A Goble SD Doss GA Tsou NN Butora G Vicario PP Ayala JM Struthers M Demartino JA Mills SG Yang L 《Bioorganic & medicinal chemistry letters》2008,18(4):1374-1377
In an effort to shed light on the active binding conformation of our 3-amino-1-alkyl-cyclopentane carboxamide CCR2 antagonists, we prepared several conformationally constrained analogs resulting from backbone cyclization. Evaluation of CCR2 binding affinities for these analogs gave insight into the optimal relative positions of the piperidine and benzylamide moieties while simultaneously leading to the discovery of a new, potent lead type based upon a spirocyclic acetal scaffold. 相似文献
997.
998.
A role for decorin in the remodeling of myocardial infarction. 总被引:3,自引:0,他引:3
Sara M Weis Scott D Zimmerman Maithili Shah James W Covell Jeffrey H Omens John Ross Nancy Dalton Ying Jones Charles C Reed Renato V Iozzo Andrew D McCulloch 《Matrix biology》2005,24(4):313-324
Because the small leucine-rich proteoglycan decorin has been implicated in regulation of collagen fibrillogenesis leading to proper extracellular matrix assembly, we hypothesized it could play a key role in cardiac fibrosis following myocardial infarction. In this study we ligated the left anterior descending coronary artery in wildtype and decorin-null mice to produce large infarcts in the anterior wall of the left ventricle. At early stages post-coronary occlusion the myocardial infarction size did not appreciably differ between the two genotypes. However, we found a wider distribution of collagen fibril sizes with less organization and loose packing in mature scar from decorin-null mice. Thus, we tested the hypothesis that these abnormal collagen fibrils would adversely affect post-infarction mechanics and ventricular remodeling. Indeed, scar size, right ventricular remote hypertrophy, and left ventricular dilatation were greater in decorin-null animals compared with wildtype littermates 14 days after acute myocardial infarction. Echocardiography revealed depressed left ventricular systolic function between 4 and 8 weeks post-ischemia in the decorin-null animals. These changes indicate that decorin is required for the proper fibrotic evolution of myocardial infarctions, and that its absence leads to abnormal scar tissue formation. This might contribute to aneurysmal ventricular dilatation, remote hypertrophy, and depressed ventricular function. 相似文献
999.
Andrew J Hamilton Nancy M Endersby Peter M Ridland Jingye Zhang Melissa Neal 《Australian Journal of Entomology》2005,44(3):284-287
Abstract We studied oviposition preference of Plutella xylostella for four cultivars of cabbage, broccoli and cauliflower in the field. There were no differences in the number of eggs found on the various cultivars of broccoli or cauliflower. Significantly more eggs were laid on cultivar Savoy King than any of the other cabbage cultivars tested. We then compared the development time and feeding damage of larvae reared on Savoy King and Green Coronet cabbages. Larvae developed more rapidly and fed more and for longer on Green Coronet than Savoy King. Thus, while Savoy King is more attractive to oviposition in the field, net impacts on the crop may be lessened to some degree through lower feeding proficiency of the larvae on that cultivar. 相似文献
1000.