A mass-balance/photochemical assessment of DMS sea-to-air flux as inferred from NASA GTE PEM-West a and B observations

This study reports dimethyl sulfide (DMS) sea-to-air fluxes derived from a mass-balance/photochemical-modeling approach. The region investigated was the western North Pacific covering the latitude range of 0°-30°N. Two NASA airborne databases were used in this study: PEM-West A in September-October 1991 and PEM-West B in February-March 1994. A total of 35 boundary layer (BL) sampling runs were recorded between the two programs. However, after filtering these data for pollution impacts and DMS lifetime considerations, this total was reduced to 13. Input for each analysis consisted of atmospheric DMS measurements, the equivalent mixing depth (EMD) for DMS, and model estimated values for OH and NO3. The evaluation of the EMD took into account both DMS within the BL as well as that transported into the overlying atmospheric buffer layer (BuL). DMS fluxes ranged from 0.6 to 3.0 μmol m-2d-1 for PEM-West A (10 sample runs) and 1.4 to 1.9 μmol m-2d-1 for PEM-West B (3 sample runs). Sensitivity analyses showed that the photochemically evaluated DMS flux was most influenced by the DMS vertical profile and the diel profile for OH. A propagation of error analysis revealed that the uncertainty associated with individual flux determinations ranged from a factor of 1.3 to 1.5. Also assessed were potential systematic errors. The first of these relates to our noninclusion of large-scale mean vertical motion as it might appear in the form of atmospheric subsidence or as a convergence. Our estimates here would place this error in the range of O to 30%. By far the largest systematic error is that associated with stochastic events (e.g., those involving major changes in cloud coverage). In the latter case, sensitivity tests suggested that the error could be as high as a factor of 2. With improvements in such areas as BL sampling time, direct observations of OH, improved DMS vertical profiling, direct assessment of vertical velocity in the field, and preflight (24 hours) detailed meteorological data, it appears that the uncertainty in this approach could be reduced to ±25%. Copyright 1999 by the American Geophysical Union

Analysis of Next-generation Sequencing Data in Virology - Opportunities and Challenges

Viruses are the most abundant and the smallest organisms, which are relatively simple to sequence. Genome sequence data of viruses for individual species to populations outnumber that of other species. Although this offers an opportunity to study viral diversity at varying levels of taxonomic hierarchy, it also poses challenges for systematic and structured organization of data and its downstream processing. Extensive computational analyses using a number of algorithms and programs have opened exciting opportunities for virus discovery and diagnostics, apart from augmenting our understanding of the intriguing world of viruses. Unravelling evolutionary dynamics of viruses permits improved understanding of phenomena such as quasispecies diversity, role of mutations in host switching and drug resistance, which enables the tangible measurements of genotype and phenotype of viruses. Improved understanding of geno-/serotype diversity in correlation with antigenic diversity will facilitate rational design and development of efficacious vaccines against emerging and re-emerging viruses. Mathematical models developed using the genomic data could be used to predict the spread of viruses due to vector switching and the (re)emergence due to host switching and, thereby, contribute towards designing public health policies for disease management and control

Global impact of nitrate photolysis in sea-salt aerosol on NOx, OH, and O3 in the marine boundary layer

Recent field studies have suggested that sea-salt particulate nitrate (NITs) photolysis may act as a significant local source of nitrogen oxides (NOx) over oceans. We present a study of the global impact of this process on oxidant concentrations in the marine boundary layer (MBL) using the GEOS-Chem model, after first updating the model to better simulate observed gas-particle phase partitioning of nitrate in the marine boundary layer. Model comparisons with long-term measurements of NOx from the Cape Verde Atmospheric Observatory (CVAO) in the eastern tropical North Atlantic provide support for an in situ source of NOx from NITs photolysis, with NITs photolysis coefficients about 25-50 times larger than corresponding HNO3 photolysis coefficients. Short-term measurements of nitrous acid (HONO) at this location show a clear daytime peak, with average peak mixing ratios ranging from 3 to 6 pptv. The model reproduces the general shape of the diurnal HONO profile only when NITs photolysis is included, but the magnitude of the daytime peak mixing ratio is under-predicted. This under-prediction is somewhat reduced if HONO yields from NITs photolysis are assumed to be close to unity. The combined NOx and HONO analysis suggests that the upper limit of the ratio of NITs : HNO3 photolysis coefficients is about 100. The largest simulated relative impact of NITs photolysis is in the tropical and subtropical marine boundary layer, with peak local enhancements ranging from factors of 5 to 20 for NOx, 1.2 to 1.6 for OH, and 1.1 to 1.3 for ozone. Since the spatial extent of the sea-salt aerosol (SSA) impact is limited, global impacts on NOx, ozone, and OH mass burdens are small ( ∼ 1-3 %). We also present preliminary analysis showing that particulate nitrate photolysis in accumulation-mode aerosols (predominantly over continental regions) could lead to ppbv-level increases in ozone in the continental boundary layer. Our results highlight the need for more comprehensive long-term measurements of NOx, and related species like HONO and sea-salt particulate nitrate, to better constrain the impact of particulate nitrate photolysis on marine boundary layer oxidant chemistry. Further field and laboratory studies on particulate nitrate photolysis in other aerosol types are also needed to better understand the impact of this process on continental boundary layer oxidant chemistry

A comparison of scavenging and deposition processes in global models: results from the WCRP Cambridge Workshop of 1995

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75543/1/j.1600-0889.2000.00980.x.pd

Fire-Related Carbon Emissions from Land Use Transitions in Southern Amazonia

Various land-use transitions in the tropics contribute to atmospheric carbon emissions, including forest conversion for small-scale farming, cattle ranching, and production of commodities such as soya and palm oil. These transitions involve fire as an effective and inexpensive means for clearing. We applied the DECAF (DEforestation CArbon Fluxes) model to Mato Grosso, Brazil to estimate fire emissions from various land-use transitions during 2001-2005. Fires associated with deforestation contributed 67 Tg C/yr (17 and 50 Tg C/yr from conversion to cropland and pasture, respectively), while conversion of savannas and existing cattle pasture to cropland contributed 17 Tg C/yr and pasture maintenance fires 6 Tg C/yr. Large clearings (>100 ha/yr) contributed 67% of emissions but comprised only 10% of deforestation events. From a policy perspective, results imply that intensification of agricultural production on already-cleared land and policies to discourage large clearings would reduce the major sources of emissions from fires in this region. Copyright 2008 by the American Geophysical Union

A novel chalcone derivative which acts as a microtubule depolymerising agent and an inhibitor of P-gp and BCRP in in-vitro and in-vivo glioblastoma models

<p>Abstract</p> <p>Background</p> <p>Over the past decades, in spite of intensive search, no significant increase in the survival of patients with glioblastoma has been obtained. The role of the blood-brain barrier (BBB) and especially the activity of efflux pumps belonging to the ATP Binding Cassette (ABC) family may, in part, explain this defect.</p> <p>Methods</p> <p>The <it>in-vitro </it>activities of JAI-51 on cell proliferation were assessed by various experimental approaches in four human and a murine glioblastoma cell lines. Using drug exclusion assays and flow-cytometry, potential inhibitory effects of JAI-51 on P-gp and BCRP were evaluated in sensitive or resistant cell lines. JAI-51 activity on <it>in-vitro </it>microtubule polymerization was assessed by tubulin polymerization assay and direct binding measurements by analytical ultracentrifugation. Finally, a model of C57BL/6 mice bearing subcutaneous GL26 glioblastoma xenografts was used to assess the activity of the title compound <it>in vivo</it>. An HPLC method was designed to detect JAI-51 in the brain and other target organs of the treated animals, as well as in the tumours.</p> <p>Results</p> <p>In the four human and the murine glioblastoma cell lines tested, 10 μM JAI-51 inhibited proliferation and blocked cells in the M phase of the cell cycle, via its activity as a microtubule depolymerising agent. This ligand binds to tubulin with an association constant of 2 × 10⁵M^-1, overlapping the colchicine binding site. JAI-51 also inhibited the activity of P-gp and BCRP, without being a substrate of these efflux pumps. These <it>in vitro </it>studies were reinforced by our <it>in vivo </it>investigations of C57BL/6 mice bearing GL26 glioblastoma xenografts, in which JAI-51 induced a delay in tumour onset and a tumour growth inhibition, following intraperitoneal administration of 96 mg/kg once a week. In accordance with these results, JAI-51 was detected by HPLC in the tumours of the treated animals. Moreover, JAI-51 was detected in the brain, showing that the molecule is also able to cross the BBB.</p> <p>Conclusion</p> <p>These <it>in vitro </it>and <it>in vivo </it>data suggest that JAI-51 could be a good candidate for a new treatment of tumours of the CNS. Further investigations are in progress to associate the title compound chemotherapy to radiotherapy in a rat model.</p

Bid Regulates the Pathogenesis of Neurotropic Reovirus

Reovirus infection leads to apoptosis in both cultured cells and the murine central nervous system (CNS). NF-κB-driven transcription of proapoptotic cellular genes is required for the effector phase of the apoptotic response. Although both extrinsic death-receptor signaling pathways and intrinsic pathways involving mitochondrial injury are implicated in reovirus-induced apoptosis, mechanisms by which either of these pathways are activated and their relationship to NF-κB signaling following reovirus infection are unknown. The proapoptotic Bcl-2 family member, Bid, is activated by proteolytic cleavage following reovirus infection. To understand how reovirus integrates host signaling circuits to induce apoptosis, we examined proapoptotic signaling following infection of Bid-deficient cells. Although reovirus growth was not affected by the absence of Bid, cells lacking Bid failed to undergo apoptosis. Furthermore, we found that NF-κB activation is required for Bid cleavage and subsequent proapoptotic signaling. To examine the functional significance of Bid-dependent apoptosis in reovirus disease, we monitored fatal encephalitis caused by reovirus in the presence and absence of Bid. Survival of Bid-deficient mice was significantly enhanced in comparison to wild-type mice following either peroral or intracranial inoculation of reovirus. Decreased reovirus virulence in Bid-null mice was accompanied by a reduction in viral yield. These findings define a role for NF-κB-dependent cleavage of Bid in the cell death program initiated by viral infection and link Bid to viral virulence

The NF-kappa B inhibitor, celastrol, could enhance the anti-cancer effect of gambogic acid on oral squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Gambogic acid (GA) is a major active ingredient of gamboge, a widely used traditional Chinese medicine that has been reported to be a potent cytotoxic agent against some malignant tumors. Many studies have shown that the NF-kappa B signaling pathway plays an important role in anti-apoptosis and the drug resistance of tumor cells during chemotherapy. In this study, the effects and mechanisms of GA and the NF-kappa B inhibitor celastrol on oral cancer cells were investigated.</p> <p>Methods</p> <p>Three human oral squamous cell carcinoma cell lines, Tca8113, TSCC and NT, were treated with GA alone, celastrol alone or GA plus celastrol. Cytotoxicity was assessed by MTT assay. The rate of apoptosis was examined with annexin V/PI staining as well as transmission electronic microscopy in Tca8113 cells. The level of constitutive NF-kappa B activity in oral squamous cell carcinoma cell lines was determined by immunofluorescence assays and nuclear extracts and electrophoretic mobility shift assays (EMSAs) <it>in vitro</it>. To further investigate the role of NF-kappa B activity in GA and celastrol treatment in oral squamous cell carcinoma, we used the dominant negative mutant SR-IκBα to inhibit NF-kappa B activity and to observe its influence on the effect of GA.</p> <p>Results</p> <p>The results showed that GA could inhibit the proliferation and induce the apoptosis of the oral squamous cell carcinoma cell lines and that the NF-kappa B pathway was simultaneously activated by GA treatment. The minimal cytotoxic dose of celastrol was able to effectively suppress the GA-induced NF-kappa B pathway activation. Following the combined treatment with GA and the minimal cytotoxic dose of celastrol or the dominant negative mutant SR-IκBα, proliferation was significantly inhibited, and the apoptotic rate of Tca8113 cells was significantly increased.</p> <p>Conclusion</p> <p>The combination of GA and celastrol has a synergistic antitumor effect. The effect can be primarily attributed to apoptosis induced by a decrease in NF-kappa B pathway activation. The NF-kappa B signaling pathway plays an important role in this process. Therefore, combining GA and celastrol may be a promising modality for treating oral squamous cell carcinoma.</p