Chigwada, Tabitha; Mbiya, Wilbes; Chipiso, Kudzanai; Simoyi, Reuben H
The reaction between tetramethylthiourea (TTTU) and slightly acidic chlorite has been studied. The reaction is much faster than comparable oxidations of the parent thiourea compound as well as other substituted thioureas. The stoichiometry of the reaction in excess oxidant showed a complete desulfurization of the thiocarbamide to yield the corresponding urea and sulfate: 2ClO2(-) + (Me2N)2C ═ S + H2O → (Me2N)2C ═ O + SO4(2-) + 2Cl(-) + 2H(+). The reaction mechanism is unique in that the most stable metabolite before formation of the corresponding urea is the S-oxide. This is one of the rare occasions in which a low-molecular-weight S-oxide has been stabilized without the aid of large steric groups. ESI-MS data show almost quantitative formation of the S-oxide and negligible formation of the sulfinic and sulfonic acids. TTTU, in contrast to other substituted thioureas, can only stabilize intermediate oxoacids, before formation of sulfate, in the form of zwitterions. With a stoichiometric excess of TTTU over oxidant, the TTTU dimer is the predominant product. Chlorine dioxide, which is formed from the reaction of excess chlorite and HOCl, is a very important reactant in the overall mechanism. It reacts rapidly with TTTU to reform ClO2(-). Oxidation of TTTU by chlorite has a complex dependence on acid as a result of chlorous acid dissociation and protonation of the thiol group on TTTU in high-acid conditions, which renders the thiol center a less effective nucleophile. PMID:24922053
Carbajo-Lozoya, Javier; Ma-Lauer, Yue; Malešević, Miroslav; Theuerkorn, Martin; Kahlert, Viktoria; Prell, Erik; von Brunn, Brigitte; Muth, Doreen; Baumert, Thomas F; Drosten, Christian; Fischer, Gunter; von Brunn, Albrecht
Until recently, there were no effective drugs available blocking coronavirus (CoV) infection in humans and animals. We have shown before that CsA and FK506 inhibit coronavirus replication (Carbajo-Lozoya, J., Müller, M.A., Kallies, S., Thiel, V., Drosten, C., von Brunn, A. Replication of human coronaviruses SARS-CoV, HCoV-NL63 and HCoV-229E is inhibited by the drug FK506. Virus Res. 2012; Pfefferle, S., Schöpf, J., Kögl, M., Friedel, C., Müller, M.A., Stellberger, T., von Dall'Armi, E., Herzog, P., Kallies, S., Niemeyer, D., Ditt, V., Kuri, T., Züst, R., Schwarz, F., Zimmer, R., Steffen, I., Weber, F., Thiel, V., Herrler, G., Thiel, H.-J., Schwegmann-Weßels, C., Pöhlmann, S., Haas, J., Drosten, C. and von Brunn, A. The SARS-Coronavirus-host interactome: identification of cyclophilins as target for pan-Coronavirus inhibitors. PLoS Pathog., 2011). Here we demonstrate that CsD Alisporivir, NIM811 as well as novel non-immunosuppressive derivatives of CsA and FK506 strongly inhibit the growth of human coronavirus HCoV-NL63 at low micromolar, non-cytotoxic concentrations in cell culture. We show by qPCR analysis that virus replication is diminished up to four orders of magnitude to background levels. Knockdown of the cellular Cyclophilin A (CypA/PPIA) gene in Caco-2 cells prevents replication of HCoV-NL63, suggesting that CypA is required for virus replication. Collectively, our results uncover Cyclophilin A as a host target for CoV infection and provide new strategies for urgently needed therapeutic approaches. PMID:24566223
Wild, M.; Ohmura, A.; Feichter, J.; Stier, P.; Robock, A.; Li, H.
Recent evidence suggests that the amount of solar radiation reaching the earth surface is not stable over time but exhibits significant decadal variations. These variations, in addition to the changes in thermal radiation induced by alterations in greenhouse gases, cause changes in radiative forcings which may significantly affect surface climate. Observations from the Global Energy Balanced Archive (GEBA) and Baseline Surface Radiation Network (BSRN) databases at the Swiss Federal Institute of Technology suggest that surface solar radiation, after decades of dimming, reversed into a brightening since the mid 1980s at widespread locations. These changes are in line with a recovery of atmospheric transparency, possibly related to reduced aerosol loadings due to air pollution control and the breakdown of industry in formerly Communist countries. Not many GCMs currently represent aerosol effects with a degree of sophistication to capture such effects, but we used a special version of the Max Planck Institute for Meteorology GCM which includes a detailed aerosol scheme, ECHAM5-HAM, to investigate the observed trends. In addition, we investigate the potential impact of the variations in surface radiation on other elements of the climate system, such as soil moisture, which shows changes in line with the changes in radiation. Reference: Wild, M., Gilgen, H., Roesch, A., Ohmura, A., Long, C., Dutton, E., Forgan, B., Kallis, A., Russak, V., Tsvetkov, A., 2005: From dimming to brightening: Decadal changes in solar radiation at the Earth's surface. Science , 308, 847-850
Castle, Paul M.; Zolman, Kevin D.; Kohout, Susy C.
The voltage-sensing phosphatase (VSP) is the first example of an enzyme controlled by changes in membrane potential. VSP has four distinct regions: the transmembrane voltage-sensing domain (VSD), the inter-domain linker, the cytosolic catalytic domain, and the C2 domain. The VSD transmits the changes in membrane potential through the inter-domain linker activating the catalytic domain which then dephosphorylates phosphatidylinositol phosphate (PIP) lipids. The role of the C2, however, has not been established. In this study, we explore two possible roles for the C2: catalysis and membrane-binding. The Ci-VSP crystal structures show that the C2 residue Y522 lines the active site suggesting a contribution to catalysis. When we mutated Y522 to phenylalanine, we found a shift in the voltage dependence of activity. This suggests hydrogen bonding as a mechanism of action. Going one step further, when we deleted the entire C2 domain, we found voltage-dependent enzyme activity was no longer detectable. This result clearly indicates the entire C2 is necessary for catalysis as well as for modulating activity. As C2s are known membrane-binding domains, we tested whether the VSP C2 interacts with the membrane. We probed a cluster of four positively charged residues lining the top of the C2 and suggested by previous studies to interact with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] (Kalli et al., 2014). Neutralizing those positive charges significantly shifted the voltage dependence of activity to higher voltages. We tested membrane binding by depleting PI(4,5)P2 from the membrane using the 5HT2C receptor and found that the VSD motions as measured by voltage clamp fluorometry (VCF) were not changed. These results suggest that if the C2 domain interacts with the membrane to influence VSP function it may not occur exclusively through PI(4,5)P2. Together, this data advances our understanding of the VSP C2 by demonstrating a necessary and critical role for the C2 domain in
Mercado, L.; Bellouin, N.; Sitch, S.; Boucher, O.; Huntingford, C.; Wild, M.; Cox, P. M.
photosynthesis for climate model applications. Tellus Series B-Chemical and Physical Meteorology, 59, 553-565. Niyogi D., Chang H.I., Saxena V.K., Holt T., Alapaty K., Booker F., Chen F., Davis K.J., Holben B., Matsui T., Meyers T., Oechel W.C., Pielke R.A., Wells R., Wilson K. & Xue Y.K. (2004) Direct observations of the effects of aerosol loading on net ecosystem CO2 exchanges over different landscapes. Geophysical Research Letters, 31. Oliveira P.H.F., Artaxo P., Pires C., De Lucca S., Procopio A., Holben B., Schafer J., Cardoso L.F., Wofsy S.C. & Rocha H.R. (2007) The effects of biomass burning aerosols and clouds on the CO2 flux in Amazonia. Tellus Series B-Chemical and Physical Meteorology, 59, 338-349. Roderick M.L., Farquhar G.D., Berry S.L. & Noble I.R. (2001) On the direct effect of clouds and atmospheric particles on the productivity and structure of vegetation. Oecologia, 129, 21-30. Stanhill G. & Cohen S. (2001) Global dimming: a review of the evidence for a widespread and significant reduction in global radiation with discussion of its probable causes and possible agricultural consequences. 107, 255-278. Wild M., Gilgen H., Roesch A., Ohmura A., Long C.N., Dutton E.G., Forgan B., Kallis A., Russak V. & Tsvetkov A. (2005) From dimming to brightening: Decadal changes in solar radiation at Earth's surface. Science, 308, 847-850.
recent absence of solar dimming may have allowed the greenhouse effect to finally develop at full size, as seen in accelerated temperature increases in the 1990s. The rate of temperature change at land surfaces has increased by an order of magnitude in the period 1985-2002 where solar dimming was absent, compared to the period with significant dimming (1958-1985). In the 1990s, more energy may therefore have been available at the surface compared to earlier decades, favoring, for example, an accelerated retreat of worldwide glaciers, or higher evaporation in areas of unlimited water supply and associated reduced soil moisture tendencies, with associated implications for the global hydrological cycle. Reference: Wild, M., Gilgen, H., Roesch, A., Ohmura, A., Long, C., Dutton, E., Forgan, B., Kallis, A., Russak, V., Tsvetkov, A., 2005: From dimming to brightening: Decadal changes in solar radiation at the Earth's surface. Science , 308, 847-850.
Jones, Julian D. C.; Tatam, Ralph P.
fibre optic gyroscope, conventionally taken to date from the first experimental demonstration by V Vali and R W Shorthill (1976 'Fibre ring interferometer' Appl. Opt. 15 1099-100). It is an indication of the health of the community that the successful maturity of some applications is complemented by the new technologies that will be the basis of the future development of the field, and here the content of this special issue is an interesting indication of likely areas of growth. Essentially all current fibre optic systems are based on solid, doped fused silica fibres, which are the basis of the world's telecommunications industry. However, over the last decade an exciting development has been micro-structured fibres, whose waveguiding properties owe as much to the structure of the fibre as to the materials from which they are made. The significance for sensing applications is considerable, with opportunities to achieve properties for dispersion, environmental sensitivity, wavelength range and power-handling quite different from the capabilities of conventional fibre. Thus it is not surprising that several of the papers in the issue (by Cordeiro, Martynkien, Bock, Wolinski, Michie, Digonnet and Kilic) are devoted to applications of such fibres—photonic crystal fibres (PCF), as they are often called. Digonnet's contribution is especially interesting, being concerned with the use of hollow-core photonic bandgap fibre to form a gyroscope, hence avoiding the many subtle non-linear optical effects that can degrade the performance of a conventional fibre gyroscope. PCF are not the only special fibres to feature in the issue: polymer fibres are of increasing interest for sensing applications (O'Keeffe, Kiesel, Kalli and Ashley), not least for their ability to withstand high levels of strain. In-fibre gratings continue to be a very important area in the field, and are well represented in the issue (Ni, González-Segura, Chen, Falate, Kamikawachi, Wang and Correia). We hope
Sellami, Haykel; Benabdallah, Sihem; La Jeunesse, Isabelle; Herrmann, Frank; Vanclooster, Marnik
. López-Moreno, J. I., Vicente-Serrano, S. M., Moran-Tejeda, E., Zabalza, J., Lorenzo-Lacruz, J., and García-Ruiz, J. M.: Impact of climate evolution and land use changes on water yield in the ebro basin, Hydrology and Earth System Sciences, 15, 311-322, 10.5194/hess-15-311-2011, 2011. Ludwig, R., Roson, R., Zografos, C., Kallis. Towards an inter-disciplinary research agenda on climate change, water and security in southern Europe and neighbouring countries. Environ. Sci. Policy. 14: 794-803, 10.1016/j.envsci.2011.04.003, 2011. Richter, B. D., Baumgartner, J.V., Powell, J., Braun, D. P.: Method for Assessing Hydrologic Alteration within Ecosystems, Conservation Biology, 10, 11, 1996. Schneider, C., Laizé, C. L. R., Acreman, M. C., and Flörke, M.: How will climate change modify river flow regimes in Europe? Hydrology and Earth System Sciences, 17, 325-339, 10.5194/hess-17-325-2013, 2013.
Tanaka, Katsumasa; Imamovic, Adel; Folini, Doris; Ohmura, Atsumu; Wild, Martin
Industrial Era. Journal of Climate, 20, 4874-4883. Ohmura A (2009) Observed decadal variations in surface solar radiation and their causes. Journal of Geophysical Research, 114, D00D05. Ohmura A, Lang H (1989) Secular variation of global radiation over Europe. In: Lenoble J, Geleyn JF, Deepak A (eds) Current Problems in Atmospheric Radiation. Hampton, pp 98-301. Shepherd JM (2005) A Review of Current Investigations of Urban-Induced Rainfall and Recommendations for the Future. Earth Interactions, 9, 1-27. Skeie RB, Berntsen TK, Myhre G, Tanaka K, Kvalevåg MM, Hoyle CR (2011) Anthropogenic radiative forcing time series from pre-industrial times until 2010. Atmospheric Chemistry and Physics, 11, 11827-11857. Wild M (2009) Global dimming and brightening: A review. Journal of Geophysical Research, 114, D00D16. Wild M, Gilgen H, Roesch A, Ohmura A, Long CN, Dutton EG, Forgan B, Kallis A, Russak V, Tsvetkov A (2005) From Dimming to Brightening: Decadal Changes in Solar Radiation at Earth's Surface. Science, 308, 847-850.