Saffold Virus, a Human Theiler's-Like Cardiovirus, Is Ubiquitous and Causes Infection Early in Life

The family Picornaviridae contains well-known human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and parechovirus). In addition, this family contains a number of viruses that infect animals, including members of the genus Cardiovirus such as Encephalomyocarditis virus (EMCV) and Theiler's murine encephalomyelits virus (TMEV). The latter are important murine pathogens that cause myocarditis, type 1 diabetes and chronic inflammation in the brains, mimicking multiple sclerosis. Recently, a new picornavirus was isolated from humans, named Saffold virus (SAFV). The virus is genetically related to Theiler's virus and classified as a new species in the genus Cardiovirus, which until the discovery of SAFV did not contain human viruses. By analogy with the rodent cardioviruses, SAFV may be a relevant new human pathogen. Thus far, SAFVs have sporadically been detected by molecular techniques in respiratory and fecal specimens, but the epidemiology and clinical significance remained unclear. Here we describe the first cultivated SAFV type 3 (SAFV-3) isolate, its growth characteristics, full-length sequence, and epidemiology. Unlike the previously isolated SAFV-1 and -2 viruses, SAFV-3 showed efficient growth in several cell lines with a clear cytopathic effect. The latter allowed us to conduct a large-scale serological survey by a virus-neutralization assay. This survey showed that infection by SAFV-3 occurs early in life (>75% positive at 24 months) and that the seroprevalence reaches >90% in older children and adults. Neutralizing antibodies were found in serum samples collected in several countries in Europe, Africa, and Asia. In conclusion, this study describes the first cultivated SAFV-3 isolate, its full-length sequence, and epidemiology. SAFV-3 is a highly common and widespread human virus causing infection in early childhood. This finding has important implications for understanding the impact of these ubiquitous viruses and their possible role in acute and/or chronic disease

Characterization of cell death induced by vinflunine, the most recent Vinca alkaloid in clinical development

Vinflunine, the most recent Vinca alkaloid in clinical development, demonstrated superior antitumour activity to other Vincas in preclinical tumour models. This study aimed to define its molecular mechanisms of cell killing in both parental sensitive and vinflunine-resistant P388 leukaemia cells. Vinflunine treatment of these cells resulted in apoptosis characterized by DNA fragmentation and proteolytic cleavage of poly-(ADP-ribose) polymerase. Apoptosis-inducing concentrations of vinflunine caused c-Jun N-terminal kinase 1 stimulation, as well as caspases-3/7 activation. This activation of caspases and the induction of apoptosis could be inhibited by the caspase inhibitor acetyl-Asp-Glu-Val-Asp-aldehyde. Interestingly, the apoptosis signal triggered by vinflunine in these P388 cells was not mediated through Bcl-2 phosphorylation. In addition, when vinflunine resistance was developed in P388 cells, it was associated with resistance to vinflunine-induced apoptosis, as reflected by a loss of capacity to induce DNA fragmentation and PARP degradation, and characterized by increased levels of Bcl-2 and Bfl-1/A1. Therefore, these data indirectly implicate Bcl-2 and Bfl-1/A1 in vinflunine-induced cell death mechanisms

Satellite confirmation of the dominance of chlorofluorocarbons in the global stratospheric chlorine budget

OBSERVED increases in concentrations of chlorine in the stratosphere1-7 have been widely implicated in the depletion of lower-stratospheric ozone over the past two decades8-14. The present concentration of stratospheric chlorine is more than five times that expected from known natural 'background' emissions from the oceans and biomass burning15-18, and the balance has been estimated to be dominantly anthropogenic in origin, primarily due to the breakdown products of chlorofluorocarbons (CFCs)19,20. But despite the wealth of scientific data linking chlorofluorocarbon emissions to the observed chlorine increases, the political sensitivity of the ozone-depletion issue has generated a re-examination of the evidence21,22. Here we report a four-year global time series of satellite observations of hydrogen chloride (HCl) and hydrogen fluoride (HF) in the stratosphere, which shows conclusively that chlorofluorocarbon releases - rather than other anthropogenic or natural emissions - are responsible for the recent global increases in stratospheric chlorine concentrations. Moreover, all but a few per cent of observed stratospheric chlorine amounts can be accounted for by known natural and anthropogenic tropospheric emissions. Altogether, these results implicate the chlorofluorocarbon s beyond reasonable doubt as dominating ozone depletion in the lower stratosphere

Short-Lived Trace Gases in the Surface Ocean and the Atmosphere

The two-way exchange of trace gases between the ocean and the atmosphere is important for both the chemistry and physics of the atmosphere and the biogeochemistry of the oceans, including the global cycling of elements. Here we review these exchanges and their importance for a range of gases whose lifetimes are generally short compared to the main greenhouse gases and which are, in most cases, more reactive than them. Gases considered include sulphur and related compounds, organohalogens, non-methane hydrocarbons, ozone, ammonia and related compounds, hydrogen and carbon monoxide. Finally, we stress the interactivity of the system, the importance of process understanding for modeling, the need for more extensive field measurements and their better seasonal coverage, the importance of inter-calibration exercises and finally the need to show the importance of air-sea exchanges for global cycling and how the field fits into the broader context of Earth System Science

Methyl iodide: Atmospheric budget and use as a tracer of marine convection in global models

[1] We simulate the oceanic and atmospheric distribution of methyl iodide (CH3I) with a global 3-D model driven by assimilated meteorological observations from the Goddard Earth Observing System of the NASA Data Assimilation Office and coupled to an oceanic mixed layer model. A global compilation of atmospheric and oceanic observations is used to constrain and evaluate the simulation. Seawater CH3I(aq) in the model is produced photochemically from dissolved organic carbon, and is removed by reaction with Cl- and emission to the atmosphere. The net oceanic emission to the atmosphere is 214 Gg yr-1. Small terrestrial emissions from rice paddies, wetlands, and biomass burning are also included in the model. The model captures 40% of the variance in the observed seawater CH3I(aq) concentrations. Simulated concentrations at midlatitudes in summer are too high, perhaps because of a missing biological sink of CH3I(aq). We define a marine convection index (MCI) as the ratio of upper tropospheric (8-12 km) to lower tropospheric (0-2.5 km) CH3I concentrations averaged over coherent oceanic regions. The MCI in the observations ranges from 0.11 over strongly subsiding regions (southeastern subtropical Pacific) to 0.40 over strongly upwelling regions (western equatorial Pacific). The model reproduces the observed MCI with no significant global bias (offset of only +11%) but accounts for only 15% of its spatial and seasonal variance. The MCI can be used to test marine convection in global models, complementing the use of radon-222 as a test of continental convection. Copyright 2002 by the American Geophysical Union