Effect of Sediment on the Fate of Metolachlor and Atrazine in Surface Water

In aquatic environments, pesticides can partition between the dissolved phase and particulate phase depending on the type of suspended sediment present and the physical and chemical properties of the pesticides and water. Particulate matter and sediment can alter the bioavailability of contaminants to organisms and therefore influence their toxicity and availability for microbial degradation. Experiments were conducted to determine the degradation of atrazine (6-chloro-N-ethyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine) and metolachlor (2-chloro-N-(2-ethyl-6-methylphenyl)-N-(methooxyprop-2-yl)acetamide) in surface water, and to evaluate the contribution of sediment to their dissipation. Sediment significantly reduced concentrations of atrazine and metolachlor in the surface water as a result of greater degradation, evident by increased quantities of degradates in the surface water, and the partitioning of the herbicide or herbicide degradates in the sediment. First-order 50% dissipation time (DT50) values for atrazine and metolachlor were 42 and 8 d in the surface water-sediment incubation systems, which were almost four times less than the DT50s calculated for the sediment-free systems. The results of this research illustrate the importance of sediment in the fate of pesticides in surface water. Greater comprehension of the role of sediment to sequester or influence degradation of agrichemicals in aquatic systems will provide a better understanding of the bioavailability and potential toxicity of these contaminants to aquatic organisms

Sulindac metabolites inhibit epidermal growth factor receptor activation and expression

BACKGROUND: Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a decreased mortality from colorectal cancer (CRC). NSAIDs induce apoptotic cell death in colon cancer cells in vitro and inhibit growth of neoplastic colonic mucosa in vivo however, the biochemical mechanisms required for these growth inhibitory effects are not well defined. We previously reported that metabolites of the NSAID sulindac downregulate extracellular-signal regulated kinase 1/2 (ERK1/2) signaling and that this effect is both necessary and sufficient for the apoptotic effects of these drugs. The goal of this project was to specifically test the hypothesis that sulindac metabolites block activation and/or expression of the epidermal growth factor (EGF) receptor (EGFR). METHODS: HT29 human colon cancer cells were treated with EGF, alone, or in the presence of sulindac sulfide or sulindac sulfone. Cells lysates were assayed by immunoblotting for phosphorylated EGFR (pEGFR, pY1068), total EGFR, phosphorylated ERK1/2 (pERK1/2), total ERK1/2, activated caspase-3, and α-tubulin. RESULTS: EGF treatment rapidly induced phosphorylation of both EGFR and ERK1/2 in HT29 colon cancer cells. Pretreatment with sulindac metabolites for 24 h blocked EGF-induced phosphorylation of both EGFR and ERK1/2 and decreased total EGFR protein expression. Under basal conditions, downregulation of pEGFR and total EGFR was detected as early as 12 h following sulindac sulfide treatment and persisted through at least 48 h. Sulindac sulfone induced downregulation of pEGFR and total EGFR was detected as early as 1 h and 24 h, respectively, following drug treatment, and persisted through at least 72 h. EGFR downregulation by sulindac metabolites was observed in three different CRC cell lines, occurred prior to the observed downregulation of pERK1/2 and induction of apoptosis by these drugs, and was not dependent of caspase activation. CONCLUSION: These results suggest that downregulation of EGFR signaling by sulindac metabolites may occur, at least in part, by inhibiting activation and expression of EGFR. Inhibition of EGFR signaling may account for part of the growth inhibitory and chemopreventive effects of these compounds

The observational impact of dust trapping in self-gravitating discs

We present a 3D semi-analytic model of self-gravitating discs, and include a prescription for dust trapping in the disc spiral arms. Using Monte-Carlo radiative transfer we produce synthetic ALMA observations of these discs. In doing so we demonstrate that our model is capable of producing observational predictions, and able to model real image data of potentially self-gravitating discs. For a disc to generate spiral structure that would be observable with ALMA requires that the disc's dust mass budget is dominated by millimetre and centimetre-sized grains. Discs in which grains have grown to the grain fragmentation threshold may satisfy this criterion, thus we predict that signatures of gravitational instability may be detectable in discs of lower mass than has previously been suggested. For example, we find that discs with disc-to-star mass ratios as low as $0.10$ are capable of driving observable spiral arms. Substructure becomes challenging to detect in discs where no grain growth has occurred or in which grain growth has proceeded well beyond the grain fragmentation threshold. We demonstrate how we can use our model to retrieve information about dust trapping and grain growth through multi-wavelength observations of discs, and using estimates of the opacity spectral index. Applying our disc model to the Elias 27, WaOph 6 and IM Lup systems we find gravitational instability to be a plausible explanation for the observed substructure in all 3 discs, if sufficient grain growth has indeed occurred.Comment: 19 pages, 21 figures, accepted for publication in MNRA

Reduced expression of mitochondrial fumarate hydratase in progressive multiple sclerosis contributes to impaired in vitro mesenchymal stromal cell-mediated neuroprotection

BACKGROUND: Cell-based therapies for multiple sclerosis (MS), including those employing autologous bone marrow-derived mesenchymal stromal cells (MSC) are being examined in clinical trials. However, recent studies have identified abnormalities in the MS bone marrow microenvironment. OBJECTIVE: We aimed to compare the secretome of MSC isolated from control subjects (C-MSC) and people with MS (MS-MSC) and explore the functional relevance of findings. METHODS: We employed high throughput proteomic analysis, enzyme-linked immunosorbent assays and immunoblotting, as well as in vitro assays of enzyme activity and neuroprotection. RESULTS: We demonstrated that, in progressive MS, the MSC secretome has lower levels of mitochondrial fumarate hydratase (mFH). Exogenous mFH restores the in vitro neuroprotective potential of MS-MSC. Furthermore, MS-MSC expresses reduced levels of fumarate hydratase (FH) with downstream reduction in expression of master regulators of oxidative stress. CONCLUSIONS: Our findings are further evidence of dysregulation of the bone marrow microenvironment in progressive MS with respect to anti-oxidative capacity and immunoregulatory potential. Given the clinical utility of the fumaric acid ester dimethyl fumarate in relapsing–remitting MS, our findings have potential implication for understanding MS pathophysiology and personalised therapeutic intervention