Characterization of the Vasoactivity of Tachykinins in Isolated Rat Kidney: Functional Studies and in Vitro Receptor Autoradiography

Although tachykinins have potent vascular actions, their effect on renal resistance blood vessels is currently unknown. The vasoactive properties of tachykinins and related analogs were assessed in isolated perfused rat kidney. At a basal perfusion pressure (PP) of 75 $\pm$ 6 mm Hg (n = 5), bolus injections of substance P (SP) had no significant vasoactive effect. Following a sustained increase in baseline PP (134 $\pm$ 10 mm Hg) produced by phenylephrine (1 $\mu$M), SP evoked a dose-dependent increase in PP. The largest dose of SP increased PP by 60 $\pm$ 5 mm Hg. The vasoconstrictor response to SP was not blocked by phentolamine when angiotensin II was used to increase basal tone. Thus, the response to SP is not mediated by norepinephrine. Pressor responses to SP were not potentiated by peptidase inhibitors, captopril and thiorphan. SP(1-7) had no effect on PP, suggesting that the pressor response to SP is C-terminal dependent and tachykinin receptor mediated. The selective NK-1 receptor agonist, (Sar\sp9,Met(O\sb2)\sp{11}\rbrackSP, had no effect on PP. In contrast, both the selective NK-2 and NK-3 receptor agonists, GR-64349 and (MePhe\sp7) NKB, produced dose-dependent pressor responses (116 $\pm$ 8 and 134 $\pm$ 15 mm Hg increases in PP at 33 nmol, respectively) and were more potent than SP. Infusion of capsaicin (500 nM) produced an initial increase in PP following by a more prolonged decrease in PP. Clamping the renal vein produced a marked increase in PP. The localization of NK-3 receptors in rat kidney evaluated by film autoradiography using \sp{125}I- (MePhe\sp7\rbrackNKB revealed a high density of specific binding sites on the proximal ureter and renal pelvis, moderate density in the renal vein and its large branches, and a low density in the inner strip of outer medulla, but no specific binding on the renal artery system and cortex. High resolution autoradiograms demonstrated \sp{125}I- (MePhe\sp7\rbrackNKB binding sites on the tunica media of the renal vein and tunica muscularises of renal pelvis and ureter. Specific binding of \sp{125}I-BHSP was found in association with the renal artery and renal pelvis. No specific SP binding sites were associated with renal vein. These data indicate that the pressor effect of tachykinins in the isolated rat kidney can be mediated by NK-2 and/or NK-3 receptors. The latter may be on the vascular smooth muscle of the renal vein

Superconducting Properties of Copper Oxide High-Temperature Superconductors

The equations for the magnon pairing theory of high-temperature copper-oxide-based superconductors are solved and used to calculate several properties, leading to results for specific heat and critical magnetic fields consistent with experimental results. In addition, the theory suggests an explanation of why there are two sets of transition temperatures (Tcapprox 90 K and Tcapprox 55 K) for the Y1Ba2Cu3O6+x class of superconductors. It also provides an explanation of why La2-xSrxCuO4 is a superconductor for only a small range of x (and suggests an experiment to independently test the theory). These results provide support for the magnon pairing theory of high-temperature superconductors. On the basis of the theory, some suggestions are made for improving these materials. The agreement with experiment for various properties predicted by using the magnon pairing model of superconductivity provides strong support for the validity of this model for the Cu--O systems. All quantities are related to the fundamental parameters of the system (Jdd, JOCu, band structure). Some approximations have been made in the solutions to these equations. Nevertheless, the fundamental parameters are well defined, and hence improved calculational approximations will eventually lead to precise predictions of all properties. In this theory, the superconducting properties are related to fundamental structural, chemical, and physical properties, allowing one to use qualitative reasoning in contemplating how to improve the properties

Identification and evaluation of the role of the manganese efflux protein in Deinococcus radiodurans

<p>Abstract</p> <p>Background</p> <p><it>Deinococcus radiodurans </it>accumulates high levels of manganese ions, and this is believed to be correlated with the radiation resistance ability of this microorganism. However, the maintenance of manganese ion homeostasis in <it>D. radiodurans </it>remains to be investigated.</p> <p>Results</p> <p>In this study, we identified the manganese efflux protein (MntE) in <it>D. radiodurans</it>. The null mutant of <it>mntE </it>was more sensitive than the wild-type strain to manganese ions, and the growth of the <it>mntE </it>mutant was delayed in manganese-supplemented media. Furthermore, there was a substantial increase in the <it>in vivo </it>concentration of manganese ions. Consistent with these characteristics, the <it>mntE </it>mutant was more resistant to H₂O₂, ultraviolet rays, and γ-radiation. The intracellular protein oxidation (carbonylation) level of the mutant strain was remarkably lower than that of the wild-type strain.</p> <p>Conclusions</p> <p>Our results indicated that <it>dr1236 </it>is indeed a <it>mntE </it>homologue and is indispensable for maintaining manganese homeostasis in <it>D. radiodurans</it>. The data also provide additional evidence for the involvement of intracellular manganese ions in the radiation resistance of <it>D. radiodurans</it>.</p

Identification and evaluation of the role of the manganese efflux protein in Deinococcus radiodurans

<p>Abstract</p> <p>Background</p> <p><it>Deinococcus radiodurans </it>accumulates high levels of manganese ions, and this is believed to be correlated with the radiation resistance ability of this microorganism. However, the maintenance of manganese ion homeostasis in <it>D. radiodurans </it>remains to be investigated.</p> <p>Results</p> <p>In this study, we identified the manganese efflux protein (MntE) in <it>D. radiodurans</it>. The null mutant of <it>mntE </it>was more sensitive than the wild-type strain to manganese ions, and the growth of the <it>mntE </it>mutant was delayed in manganese-supplemented media. Furthermore, there was a substantial increase in the <it>in vivo </it>concentration of manganese ions. Consistent with these characteristics, the <it>mntE </it>mutant was more resistant to H₂O₂, ultraviolet rays, and γ-radiation. The intracellular protein oxidation (carbonylation) level of the mutant strain was remarkably lower than that of the wild-type strain.</p> <p>Conclusions</p> <p>Our results indicated that <it>dr1236 </it>is indeed a <it>mntE </it>homologue and is indispensable for maintaining manganese homeostasis in <it>D. radiodurans</it>. The data also provide additional evidence for the involvement of intracellular manganese ions in the radiation resistance of <it>D. radiodurans</it>.</p

Wide-spectrum optical synthetic aperture imaging via spatial intensity interferometry

High resolution imaging is achieved using increasingly larger apertures and successively shorter wavelengths. Optical aperture synthesis is an important high-resolution imaging technology used in astronomy. Conventional long baseline amplitude interferometry is susceptible to uncontrollable phase fluctuations, and the technical difficulty increases rapidly as the wavelength decreases. The intensity interferometry inspired by HBT experiment is essentially insensitive to phase fluctuations, but suffers from a narrow spectral bandwidth which results in a lack of effective photons. In this study, we propose optical synthetic aperture imaging based on spatial intensity interferometry. This not only realizes diffraction-limited optical aperture synthesis in a single shot, but also enables imaging with a wide spectral bandwidth, which greatly improves the optical energy efficiency of intensity interferometry. And this method is insensitive to the optical path difference between the sub-apertures. Simulations and experiments present optical aperture synthesis diffraction-limited imaging through spatial intensity interferometry in a 100 nm spectral width of visible light, whose maximum optical path difference between the sub-apertures reaches 69λ. This technique is expected to provide a solution for optical aperture synthesis over kilometer-long baselines at optical wavelengths

Nutlin-3 overcomes arsenic trioxide resistance and tumor metastasis mediated by mutant p53 in Hepatocellular Carcinoma

Background: Arsenic trioxide has been demonstrated as an effective anti-cancer drug against leukemia and solid tumors both in vitro and in vivo. However, recent phase II trials demonstrated that single agent arsenic trioxide was poorly effective against hepatocellular carcinoma (HCC), which might be due to drug resistance. Methods: Mutation detection of p53 gene in arsenic trioxide resistant HCC cell lines was performed. The therapeutic effects of arsenic trioxide and Nutlin-3 on HCC were evaluated both in vitro and in vivo. A series of experiments including MTT, apoptosis assays, co-Immunoprecipitation, siRNA transfection, lentiviral infection, cell migration, invasion, and epithelial-mesenchy-mal transition (EMT) assays were performed to investigate the underlying mechanisms. Results: The acquisition of p53 mutation contributed to arsenic trioxide resistance and enhanced metastatic potential of HCC cells. Mutant p53 (Mutp53) silence could re-sensitize HCC resistant cells to arsenic trioxide and inhibit the metastatic activities, while mutp53 overexpression showed the opposite effects. Neither arsenic trioxide nor Nutlin-3 could exhibit obvious effects against arsenic trioxide resistant HCC cells, while combination of them showed significant effects. Nutlin-3 can not only increase the intracellular arsenicals through inhibition of p-gp but also promote the p73 activation and mutp53 degradation mediated by arsenic trioxide. In vivo experiments indicated that Nutlin-3 can potentiate the antitumor activities of arsenic trioxide in an orthotopic hepatic tumor model and inhibit the metastasis to lung. Conclusions: Acquisitions of p53 mutations contributed to the resistance of HCC to arsenic trioxide. Nutlin-3 could overcome arsenic trioxide resistance and inhibit tumor metastasis through p73 activation and promoting mutant p53 degradation mediated by arsenic trioxide

Role of ST-Segment Resolution Alone and in Combination With TIMI Flow After Primary Percutaneous Coronary Intervention for ST-Segment–Elevation Myocardial Infarction

BACKGROUND: To evaluate the role of ST-segment resolution (STR) alone and in combination with Thrombolysis in Myocardial Infarction (TIMI) flow in reperfusion evaluation after primary percutaneous coronary intervention (PPCI) for ST-segment– elevation myocardial infarction by investigating the long-term prognostic impact.METHODS AND RESULTS: From January 2013 through September 2014, we studied 5966 patients with ST-segment–elevation myocardial infarction enrolled in the CAMI (China Acute Myocardial Infarction) registry with available data of STR evaluated at 120 minutes after PPCI. Successful STR included STR ≥50% and complete STR (ST-segment back to the equipotential line). After PPCI, the TIMI flow was assessed. The primary outcome was 2-year all-cause mortality. STR &lt; 50%, STR ≥50%, and complete STR occurred in 20.6%, 64.3%, and 15.1% of patients, respectively. By multivariable analysis, STR ≥50% (5.6%; adjusted hazard ratio [HR], 0.45 [95% CI, 0.36–0.56]) and complete STR (5.1%; adjusted HR, 0.48 [95% CI, 0.34–0.67]) were significantly associated with lower 2-year mortality than STR &lt;50% (11.7%). Successful STR was an independent predictor of 2-year mortality across the spectrum of clinical variables. After combining TIMI flow with STR, different 2-year mortality was observed in subgroups, with the lowest in successful STR and TIMI 3 flow, intermediate when either of these measures was reduced, and highest when both were abnormal.CONCLUSIONS: Post-PPCI STR is a robust long-term prognosticator for ST-segment–elevation myocardial infarction, whereas the integrated analysis of STR plus TIMI flow yields incremental prognostic information beyond either measure alone, support-ing it as a convenient and reliable surrogate end point for defining successful PPCI.</p