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921.
Prasad V. Chaturvedula Stephen E. Mercer Sokhom S. Pin George Thalody Cen Xu Charlie M. Conway Deborah Keavy Laura Signor Glenn H. Cantor Neil Mathias Paul Moench Rex Denton Robert Macci Richard Schartman Valerie Whiterock Carl Davis John E. Macor Gene M. Dubowchik 《Bioorganic & medicinal chemistry letters》2013,23(11):3157-3161
Calcitonin gene-related peptide (CGRP) receptor antagonists have been shown to be efficacious as abortive migraine therapeutics with the absence of cardiovascular liabilities that are associated with triptans. Herein, we report the discovery of a highly potent CGRP receptor antagonist, BMS-742413, with the potential to provide rapid onset of action through intranasal delivery. The compound displays excellent aqueous solubility, oxidative stability, and toxicological profile. BMS-742413 has good intranasal bioavailability in the rabbit and shows a robust, dose-dependent inhibition of CGRP-induced increases in marmoset facial blood flow. 相似文献
922.
Satinder S. Rawat Mathias Viard Stephen A. Gallo Alan Rein Robert Blumenthal Anu Puri 《Molecular membrane biology》2013,30(3):243-254
Enveloped animal viruses infect host cells by fusion of viral and target membranes. This crucial fusion event occurs either with the plasma membrane of the host cells at the physiological pH or with the endosomal membranes at low pH and is triggered by specific glycoproteins in the virus envelope. Both lipids and proteins play critical and co-operative roles in the fusion process. Interactions of viral proteins with their receptors direct which membranes fuse and viral fusion proteins then drive the process. These fusion proteins operate on lipid assemblies, whose physical and mechanical properties are equally important to the proper functioning of the process. Lipids contribute to the viral fusion process by virtue of their distinct chemical structure, composition and/or their preferred partitioning into specific microdomains in the plasma membrane called 'rafts'. An involvement of lipid rafts in viral entry and membrane fusion has been examined recently. However, the mechanism(s) by which lipids as dynamic raft components control viral envelope-glycoprotein-triggered fusion is not clear. This paper will review literature findings on the contribution of the two raft-associated lipids, cholesterol and sphingolipids in viral entry. 相似文献
923.
Ottosen Mathias Mackenzie Stephen G. Wallace Michael Kyriazakis Ilias 《The International Journal of Life Cycle Assessment》2020,25(3):523-537
The International Journal of Life Cycle Assessment - The environmental impacts (EIs) of the global pig production sector are expected to increase with increasing global pork demand. Although the... 相似文献
924.
Stepan H Philipp A Roth I Kralisch S Jank A Schaarschmidt W Lössner U Kratzsch J Blüher M Stumvoll M Fasshauer M 《Regulatory peptides》2011,168(1-3):69-72
Preeclampsia is a serious cardiovascular complication in pregnancy which is associated with an increased future metabolic and cardiovascular risk for mother and newborn. Recently, chemerin was introduced as a novel adipokine inducing insulin resistance in vitro and in vivo. In the current study, we investigated serum concentrations of chemerin by ELISA in control and preeclampsia patients during pregnancy (Control: n=37, preeclampsia: n=37) and 6 months after delivery (Control: n=35, preeclampsia: n=36). Furthermore, the association between chemerin and markers of renal function, glucose and lipid metabolism, as well as inflammation was studied in pregnant patients. Median maternal chemerin concentrations were significantly elevated in preeclampsia patients (249.5 [range: 123.1-366.9] μg/l) as compared to controls (204.8 [138.5-280.8] μg/l) (p<0.001). Furthermore, chemerin serum levels positively correlated with blood pressure, creatinine, free fatty acids, cholesterol, triglycerides (TG), leptin, adiponectin, and C-reactive protein in univariate analyses. In multivariate analyses, TG and leptin remained independently associated with circulating chemerin. Interestingly, median chemerin concentrations 6 months after delivery remained significantly higher in former preeclampsia patients (196.0 [119.8-368.7] μg/l) as compared to controls (152.2 [102.8-216.4] μg/l). Taken together, maternal chemerin serum concentrations are significantly increased in preeclampsia during and after pregnancy. Furthermore, TG and leptin are independent predictors of circulating chemerin during pregnancy. 相似文献
925.
Sergeeva NN Donnier-Marechal M Vaz G Davies AM Senge MO 《Journal of inorganic biochemistry》2011,105(12):1589-1595
Novel phenanthroline derivatives and their europium(III) and zinc(II) complexes have been prepared in up to 92%. In contrast to the stable zinc complexes, the europium compounds exhibit a strong luminescence in THF solution. However, quenching of the emission is observed in DMSO indicating complete dissociation of the complexes back to free ligands in this solvent. 1H NMR studies of the Eu(III)-complexes 5 and 6 also confirmed the existence of different states depending on the solvent used. Moreover, it was found that compound 5 is stable in EtOH-PBS solutions; here a strong signal in the emission spectra corresponding to the europium ion was detected. No spectral changes were observed for the zinc(II) complexes, they were shown to be stable in the media. These metal complexes can be used as fluorescence markers for the diagnosis of oesophageal squamous carcinoma (OE21) cells at low concentrations. Cell images were acquired using the compounds 5, 7-9 as luminescent agents. The first images were taken already after 20 min incubation time at a very low concentration range (0.7-1.6 μM). 相似文献
926.
Quintana A Pasche M Junker C Al-Ansary D Rieger H Kummerow C Nuñez L Villalobos C Meraner P Becherer U Rettig J Niemeyer BA Hoth M 《The EMBO journal》2011,30(19):3895-3912
Cell polarization enables restriction of signalling into microdomains. Polarization of lymphocytes following formation of a mature immunological synapse (IS) is essential for calcium-dependent T-cell activation. Here, we analyse calcium microdomains at the IS with total internal reflection fluorescence microscopy. We find that the subplasmalemmal calcium signal following IS formation is sufficiently low to prevent calcium-dependent inactivation of ORAI channels. This is achieved by localizing mitochondria close to ORAI channels. Furthermore, we find that plasma membrane calcium ATPases (PMCAs) are re-distributed into areas beneath mitochondria, which prevented PMCA up-modulation and decreased calcium export locally. This nano-scale distribution-only induced following IS formation-maximizes the efficiency of calcium influx through ORAI channels while it decreases calcium clearance by PMCA, resulting in a more sustained NFAT activity and subsequent activation of T cells. 相似文献
927.
Schneider CC Götz C Hessenauer A Günther J Kartarius S Montenarh M 《Molecular and cellular biochemistry》2011,356(1-2):177-184
Protein kinase CK2 is implicated in the regulation of the cell cycle. In addition to a variety of functions, CK2 has anti-apoptotic properties. So far the role of CK2 linking both pathways in the cell is not clear. Some years ago we found that CK2 phosphorylates cdc25C, one member of the cdc25 family of proteins. In this study, we showed that inhibition of CK2 activity by three different inhibitors led to a down-regulation of the level of cdc25C. Inhibition of CK2 activity by transfecting the dominant-negative CK2α subunit also resulted in a down-regulation of the level of cdc25C whereas inhibition of CK2α' had no effect on the cdc25C level. In both cases, we observed apoptosis by PARP cleavage as well as by an increase in γH2AX phosphorylation. These results show that down-regulation of the level of cdc25C is not a prerequisite for the induction of apoptosis. 相似文献
928.
To understand what governs the patterns of net ecosystem exchange of CO2, an understanding of factors influencing the component fluxes, ecosystem respiration and gross primary production is needed. In the present paper, we introduce an alternative method for estimating daytime ecosystem respiration based on whole ecosystem fluxes from a linear regression of photosynthetic photon flux density data vs. daytime net ecosystem exchange data at forest ecosystem level. This method is based on the principles of the Kok-method applied at leaf level for estimating daytime respiration. We demonstrate the method with field data and provide a discussion of the limitations of the method. 相似文献
929.
Baumert M Schlaich MP Nalivaiko E Lambert E Sari CI Kaye DM Elser MD Sanders P Lambert G 《American journal of physiology. Heart and circulatory physiology》2011,300(4):H1412-H1417
Elevated QT interval variability is a predictor of malignant ventricular arrhythmia, but the underlying mechanisms are incompletely understood. A recent study in dogs with pacing-induced heart failure suggests that QT variability is linked to cardiac sympathetic nerve activity. The aim of this study was to determine whether increased cardiac sympathetic activity is associated with increased beat-to-beat QT interval variability in patients with essential hypertension. We recorded resting norepinephrine (NE) spillover into the coronary sinus and single-lead, short-term, high-resolution, body-surface ECG in 23 patients with essential hypertension and 9 normotensive control subjects. To assess beat-to-beat QT interval variability, we calculated the overall QT variability (QTVN) as well as the QT variability index (QTVi). Cardiac NE spillover (12.2 ± 6.5 vs. 20.7 ± 14.7, P = 0.03) and QTVi (-1.75 ± 0.36 vs. -1.42 ± 0.50, P = 0.05) were significantly increased in hypertensive patients compared with normotensive subjects. QTVN was significantly correlated with cardiac NE spillover (r(2) = 0.31, P = 0.001), with RR variability (r(2) = 0.20, P = 0.008), and with systolic blood pressure (r(2) = 0.16, P = 0.02). Linear regression analysis identified the former two as independent predictors of QTVN. In conclusion, elevated repolarization lability is directly associated with sympathetic cardiac activation in patients with essential hypertension. 相似文献
930.