Wind and thermal conditions along the equatorial Pacific

Variability in heat storage of the equatorial Pacific Ocean during El Nino Southern Oscillation episodes is analyzed from subsurface temperature observations in order to show how the patterns of heat content are related to changes in the Walker Circulation. Large-scale zonal gradients in depth of the thermocline (and dynamic height) are largely in equilibrium with local zonal wind stress. Depth of the thermocline is positively correlated with mixed layer heat content and sea-surface temperature in the central Pacific during a minor El Nino/Southern Oscillation episode in 1969, indicating that the oceanic dynamic response to wind forcing as well as thermodynamic response to surface heat fluxes influence local heat storage. The distribution of heat in the mixed layer along the equator has distinctive patterns associated with pre-El Nino and mature El Nino stages. Heat is accumulated in the western Pacific during the first stage and in the central Pacific during the second. The shift in pattern is associated with a change in direction of zonal wind stress in the western Pacific. Rainfall observations show that the ascending branch of the Walker cell is always located over the region where heat is accumulated in the ocean. These observations are incorporated into a hypothetical model of the mechanism by which the equatorial ocean and atmosphere become locked into an anomalous pattern during El Nino periods

Retarded photooxidation of cyamemazine in biomimetic microenvironments

Cyamemazine (CMZ) is a neuroleptic drug that mediates cutaneous phototoxicity in humans. Here, the photobehavior of CMZ has been examined within (1)-acid glycoproteins, - and -cyclodextrins and SDS micelles. In all these microenvironments, CMZ emission was enhanced and blue-shifted, and its lifetime was longer. Irradiation of the entrapped drug at 355nm, under air; led to the N,S-dioxide. Within glycoproteins or SDS micelles the reaction was clearly slower than in phosphate buffered solution (PBS); protection by cyclodextrins was less marked. Transient absorption spectroscopy in PBS revealed formation of the triplet state ((3)CMZ*) and the radical cation (CMZ(+center dot)). Upon addition of glycoprotein, the contribution of CMZ(+center dot) became negligible, whereas (3)CMZ* dominated the spectra; in addition, the triplet lifetime became considerably longer. In cyclodextrins, this occurred to a lower extent. In all microheterogeneous systems, quenching by oxygen was slower than in solution; this was most remarkable inside glycoproteins. The highest protection from photooxidation was achieved inside SDS micelles. The results are consistent with photooxidation of CMZ through photoionization and subsequent trapping of the resulting radical cation by oxygen. This reaction is extremely sensitive to the medium and constitutes an appropriate probe for localization of the drug within a variety of biological compartments.Financial support from the Spanish Government (CTQ2010-14882, BES-2011-043706, JCI-2010-06204) and from the Generalitat Valenciana (PROMETEOII/2013/005) is gratefully acknowledged.Limones Herrero, D.; Pérez Ruiz, R.; Jiménez Molero, MC.; Miranda Alonso, MÁ. (2014). Retarded photooxidation of cyamemazine in biomimetic microenvironments. Photochemistry and Photobiology. 90(5):1012-1016. https://doi.org/10.1111/php.12303S10121016905Feinberg, A. P., & Snyder, S. H. (1975). Phenothiazine drugs: structure-activity relationships explained by a conformation that mimics dopamine. Proceedings of the National Academy of Sciences, 72(5), 1899-1903. doi:10.1073/pnas.72.5.1899Jaszczyszyn, A., Gąsiorowski, K., Świątek, P., Malinka, W., Cieślik-Boczula, K., Petrus, J., & Czarnik-Matusewicz, B. (2012). Chemical structure of phenothiazines and their biological activity. Pharmacological Reports, 64(1), 16-23. doi:10.1016/s1734-1140(12)70726-0Domínguez, J. N., López, S., Charris, J., Iarruso, L., Lobo, G., Semenov, A., … Rosenthal, P. J. (1997). Synthesis and Antimalarial Effects of Phenothiazine Inhibitors of aPlasmodium falciparumCysteine Protease. Journal of Medicinal Chemistry, 40(17), 2726-2732. doi:10.1021/jm970266pAaron, J. J., Gaye Seye, M. D., Trajkovska, S., & Motohashi, N. (2008). Bioactive Phenothiazines and Benzo[a]phenothiazines: Spectroscopic Studies, and Biological and Biomedical Properties and Applications. Bioactive Heterocycles VII, 153-231. doi:10.1007/7081_2008_125White, N. D., & Lenz, T. L. (2013). Drug-Induced Photosensitivity and the Major Culprits. American Journal of Lifestyle Medicine, 7(3), 189-191. doi:10.1177/1559827613475575Onoue, S., Kato, M., Inoue, R., Seto, Y., & Yamada, S. (2013). Photosafety Screening of Phenothiazine Derivatives With Combined Use of Photochemical and Cassette-Dosing Pharmacokinetic Data. Toxicological Sciences, 137(2), 469-477. doi:10.1093/toxsci/kft260Albini , A. E. Fasani B. D. Glass M. E. Brown P. M. Drummond 1998 Photoreactivity versus activity of a selected class of phenothiazines: A comparative study Drugs, Photochemistry and Photostability A. Albini and E. Fasani 134 149 Royal Society of Chemistry CambridgeElisei, F., Latterini, L., Gaetano Aloisi, G., Mazzucato, U., Viola, G., Miolo, G., … Dall’Acqua, F. (2002). Excited-state Properties and In Vitro Phototoxicity Studies of Three Phenothiazine Derivatives¶. Photochemistry and Photobiology, 75(1), 11. doi:10.1562/0031-8655(2002)0752.0.co;2García, C., Piñero, L., Oyola, R., & Arce, R. (2009). Photodegradation of 2-chloro Substituted Phenothiazines in Alcohols. Photochemistry and Photobiology, 85(1), 160-170. doi:10.1111/j.1751-1097.2008.00412.xRonzani, F., Trivella, A., Arzoumanian, E., Blanc, S., Sarakha, M., Richard, C., … Lacombe, S. (2013). Comparison of the photophysical properties of three phenothiazine derivatives: transient detection and singlet oxygen production. Photochemical & Photobiological Sciences, 12(12), 2160. doi:10.1039/c3pp50246eFournier, T., Medjoubi-N, N., & Porquet, D. (2000). Alpha-1-acid glycoprotein. Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 1482(1-2), 157-171. doi:10.1016/s0167-4838(00)00153-9Safaa, E.-G., Wollert, U., & Müller, W. E. (1983). Binding of Several Phenothiazine Neuroleptics to a Common Binding Site of α1-Acid Glycoprotein, Orosomucoid. Journal of Pharmaceutical Sciences, 72(2), 202-205. doi:10.1002/jps.2600720229MIYOSHI, T., SUKIMOTO, K., & OTAGIRI, M. (1992). Investigation of the Interaction Mode of Phenothiazine Neuroleptics with α1-Acid Glycoprotein. Journal of Pharmacy and Pharmacology, 44(1), 28-33. doi:10.1111/j.2042-7158.1992.tb14358.xTaheri, S., Cogswell, L. P., Gent, A., & Strichartz, G. R. (2003). Hydrophobic and Ionic Factors in the Binding of Local Anesthetics to the Major Variant of Human α1-Acid Glycoprotein. Journal of Pharmacology and Experimental Therapeutics, 304(1), 71-80. doi:10.1124/jpet.102.042028Schill, G., Wainer, I. W., & Barkan, S. A. (1986). Chiral separations of cationic and anionic drugs on an α1-acid glycoprotein-bonded stationary phase (enantiopac®). Journal of Chromatography A, 365, 73-88. doi:10.1016/s0021-9673(01)81544-2Michishita, T., Franco, P., & Zhang, T. (2010). New approaches of LC-MS compatible method development on α1-acid glycoprotein-based stationary phase for resolution of enantiomers by HPLC. Journal of Separation Science, 33(23-24), 3627-3637. doi:10.1002/jssc.201000627Hermansson, J., & Grahn, A. (1995). Optimization of the separation of enantiomers of basic drugs retention mechanisms and dynamic modification of the chiral bonding properties on a α1-acid glycoprotein column. Journal of Chromatography A, 694(1), 57-69. doi:10.1016/0021-9673(94)00936-4Caetano, W., & Tabak, M. (2000). Interaction of Chlorpromazine and Trifluoperazine with Anionic Sodium Dodecyl Sulfate (SDS) Micelles: Electronic Absorption and Fluorescence Studies. Journal of Colloid and Interface Science, 225(1), 69-81. doi:10.1006/jcis.2000.6720Ghosh, H. N., Sapre, A. V., Palit, D. K., & Mittal, J. P. (1997). Picosecond Flash Photolysis Studies on Phenothiazine in Organic and Micellar Solution. The Journal of Physical Chemistry B, 101(13), 2315-2320. doi:10.1021/jp963028zIRIE, T., SUNADA, M., OTAGIRI, M., & UEKAMA, K. (1983). Protective mechanism of .BETA.-cyclodextrin for the hemolysis induced with phenothiazine neuroleptics in vitro. Journal of Pharmacobio-Dynamics, 6(6), 408-414. doi:10.1248/bpb1978.6.408Chankvetadze, B., Kartozia, I., Burjanadze, N., Bergenthal, D., Luftmann, H., & Blaschke, G. (2001). Enantioseperation of chiral phenothiazine derivatives in capillary electrophoresis using cyclodextrin type chiral selectors. Chromatographia, 53(S1), S290-S295. doi:10.1007/bf02490344Conilleau, V., Dompmartin, A., Michel, M., Verneuil, L., & Leroy, D. (2000). Photoscratch testing in systemic drug-induced photosensitivity. Photodermatology, Photoimmunology and Photomedicine, 16(2), 62-66. doi:10.1034/j.1600-0781.2000.d01-5.xMorlière, P., Bosca, F., Miranda, M. A., Castell, J. V., & Santus, R. (2004). Primary Photochemical Processes of the Phototoxic Neuroleptic Cyamemazine: A Study by Laser Flash Photolysis and Steady-state Irradiation¶. Photochemistry and Photobiology, 80(3), 535. doi:10.1562/2004-03-15-ra-114.1Morlière, P., Haigle, J., Aissani, K., Filipe, P., Silva, J. N., & Santus, R. (2004). An Insight into the Mechanisms of the Phototoxic Response Induced by Cyamemazine in Cultured Fibroblasts and Keratinocytes¶. Photochemistry and Photobiology, 79(2), 163. doi:10.1562/0031-8655(2004)0792.0.co;2Garcia, C., Smith, G. A., McGimpsey, W. G., Kochevar, I. E., & Redmond, R. W. (1995). Mechanism and Solvent Dependence for Photoionization of Promazine and Chlorpromazine. Journal of the American Chemical Society, 117(44), 10871-10878. doi:10.1021/ja00149a010Gao, Y., Chen, J., Zhuang, X., Wang, J., Pan, Y., Zhang, L., & Yu, S. (2007). Proton transfer in phenothiazine photochemical oxidation: Laser flash photolysis and fluorescence studies. Chemical Physics, 334(1-3), 224-231. doi:10.1016/j.chemphys.2007.03.00

Conjugation to the Cell-Penetrating Peptide TAT Potentiates the Photodynamic Effect of Carboxytetramethylrhodamine

Cell-penetrating peptides (CPPs) can transport macromolecular cargos into live cells. However, the cellular delivery efficiency of these reagents is often suboptimal because CPP-cargo conjugates typically remain trapped inside endosomes. Interestingly, irradiation of fluorescently labeled CPPs with light increases the release of the peptide and its cargos into the cytosol. However, the mechanism of this phenomenon is not clear. Here we investigate the molecular basis of the photo-induced endosomolytic activity of the prototypical CPPs TAT labeled to the fluorophore 5(6)-carboxytetramethylrhodamine (TMR).We report that TMR-TAT acts as a photosensitizer that can destroy membranes. TMR-TAT escapes from endosomes after exposure to moderate light doses. However, this is also accompanied by loss of plasma membrane integrity, membrane blebbing, and cell-death. In addition, the peptide causes the destruction of cells when applied extracellularly and also triggers the photohemolysis of red blood cells. These photolytic and photocytotoxic effects were inhibited by hydrophobic singlet oxygen quenchers but not by hydrophilic quenchers.Together, these results suggest that TAT can convert an innocuous fluorophore such as TMR into a potent photolytic agent. This effect involves the targeting of the fluorophore to cellular membranes and the production of singlet oxygen within the hydrophobic environment of the membranes. Our findings may be relevant for the design of reagents with photo-induced endosomolytic activity. The photocytotoxicity exhibited by TMR-TAT also suggests that CPP-chromophore conjugates could aid the development of novel Photodynamic Therapy agents

Polymer ultrapermeability from the inefficient packing of 2D chains

The promise of ultrapermeable polymers, such as poly(trimethylsilylpropyne) (PTMSP), for reducing the size and increasing the efficiency of membranes for gas separations remains unfulfilled due to their poor selectivity. We report an ultrapermeable polymer of intrinsic microporosity (PIM-TMN-Trip) that is substantially more selective than PTMSP. From molecular simulations and experimental measurement we find that the inefficient packing of the two-dimensional (2D) chains of PIM-TMN-Trip generates a high concentration of both small (<0.7 nm) and large (0.7–1.0 nm) micropores, the former enhancing selectivity and the latter permeability. Gas permeability data for PIM-TMN-Trip surpass the 2008 Robeson upper bounds for O2/N2, H2/N2, CO2/N2, H2/CH4 and CO2/CH4, with the potential for biogas purification and carbon capture demonstrated for relevant gas mixtures. Comparisons between PIM-TMN-Trip and structurally similar polymers with three-dimensional (3D) contorted chains confirm that its additional intrinsic microporosity is generated from the awkward packing of its 2D polymer chains in a 3D amorphous solid. This strategy of shape-directed packing of chains of microporous polymers may be applied to other rigid polymers for gas separations

Redox regulation of hepatitis C in nonalcoholic and alcoholic liver

Hepatitis C virus (HCV) is an RNA virus of the Flaviviridae family that is estimated to have infected 170 million people worldwide. HCV can cause serious liver disease in humans, such as cirrhosis, steatosis, and hepatocellular carcinoma. HCV induces a state of oxidative/nitrosative stress in patients through multiple mechanisms, and this redox perturbation has been recognized as a key player in HCV-induced pathogenesis. Studies have shown that alcohol synergizes with HCV in the pathogenesis of liver disease, and part of these effects may be mediated by reactive species that are generated during hepatic metabolism of alcohol. Furthenriore, reactive species and alcohol may influence HCV replication and the outcome of interferon therapy. Alcohol consumption has also been associated with increased sequence heterogeneity of the HCV RNA sequences, suggesting multiple modes of interaction between alcohol and HCV. This review summarizes the current understanding of oxidative and nitrosative stress during HCV infection and possible combined effects of HCV, alcohol, and reactive species in the pathogenesis of liver disease. (c) 2007 Elsevier Inc. All rights reserved