Routine water monitoring test for mutagenic compounds

We have developed a simple, relatively comprehensive method for the recovery of nonvolatile mutagenic compounds from surface waters. The method recovers compounds by sequential passage of the water sample through a silica gel bed (to mechanically filter the sample and to adsorb water-insoluble compounds such as polynuclear aromatic hydrocarbons), then a cation-exchange bed (to adsorb cationic and amphoteric compounds), and then an anion-exchange bed-all contained in a single multi-bed column of glass and teflon, the parfait column. Nonvolatile compounds not adsorbed to any of these beds (i.e., neutral, water soluble compounds) were recovered following concentration of the column effluent by vacuum distillation at < 30˚. The beds of the parfait column were separated and eluted independently. Water-soluble ionic compounds were eluted with 2 M triethylammonium carbonate, and hydrophobic compounds were eluted with acetone. Under vacuum, the acetone or the components of the triethylammonium carbonate buffer (triethylamine and C02) were removed, leaving the nonvolatile components of the water sample in the residue. Acetone residues were taken up in dimethylsulfoxide; the others were taken up S n water. Using the Ames Salmonella/microsome reversion assay, each residue was assayed for mutagenic activity. The method was evaluated by recovery of five known mutagens, benzo(a)pyrene, 4-nitroquinoline-1-oxide, ethidium bromide, nitrofurylfuramide, and sodium azide, each initially spiked into a sample of laboratory deionized water and an environmental water sample to a final concentration of less than 3 ppb. Recoveries were calculated from the mutagenic activity observed in the extracts, in comparison to the activity in parallel extracts of an unspiked water sample. Under these conditions, the parfait/distillation method was able to recover detectable mutagenic activity with three of the five mutagens tested. The method has been used to survey ten Illinois surface waters for naturally occurring mutagenic activity. Samples from two sites, the Fox River at Aurora, Illinois, and the Salt Fork Creek at Urbana, Illinois, showed significant mutagenic activity. The parfait distillation method differs from other techniques for the recovery of waterborne mutagens in its emphasis on the recovery of nonvolatile compounds and neutral water-soluble compounds. This method has a1 so detected significant mutagenic activity in samples as small as 2 gallons of water, a volume consumed by a normal person every few days. This study represents the first step in the development of a routine method for the assay of mutagens in drinking water and drinking water supplies. The results of this study and the strong correlation of mutagenic activity to carcinogenic potential raises the possibility that compounds present in surface waters may pose a chronic threat to the public's health.U.S. Department of the InteriorU.S. Geological SurveyOpe

Cucurbitacin-I (JSI-124) activates the JNK/c-Jun signaling pathway independent of apoptosis and cell cycle arrest in B Leukemic Cells

<p>Abstract</p> <p>Background</p> <p>Cucurbitacin-I (JSI-124) is potent inhibitor of JAK/STAT3 signaling pathway and has anti-tumor activity in a variety of cancer including B cell leukemia. However, other molecular targets of JSI-124 beyond the JAK/STAT3 pathway are not fully understood.</p> <p>Methods</p> <p>BJAB, I-83, NALM-6 and primary CLL cells were treated with JSI-124 as indicated. Apoptosis was measured using flow cytometry for accumulation of sub-G1 phase cells (indicator of apoptosis) and Annexin V/PI staining. Cell cycle was analyzed by FACS for DNA content of G1 and G2 phases. Changes in phosphorylation and protein expression of p38, Erk1/2, JNK, c-Jun, and XIAP were detected by Western blot analysis. STAT3 and c-Jun genes were knocked out using siRNA transfection. VEGF expression was determined by mRNA and protein levels by RT-PCR and western blotting. Streptavidin Pull-Down Assay was used to determine c-Jun binding to the AP-1 DNA binding site.</p> <p>Results</p> <p>Herein, we show that JSI-124 activates c-Jun N-terminal kinase (JNK) and increases both the expression and serine phosphorylation of c-Jun protein in the B leukemic cell lines BJAB, I-83 and NALM-6. JSI-124 also activated MAPK p38 and MAPK Erk1/2 albeit at lower levels than JNK activation. Inhibition of the JNK signaling pathway failed to effect cell cycle arrest or apoptosis induced by JSI-124 but repressed JSI-124 induced c-Jun expression in these leukemia cells. The JNK pathway activation c-Jun leads to transcriptional activation of many genes. Treatment of BJAB, I-83, and NALM-6 cells with JSI-124 lead to an increase of Vascular Endothelial Growth Factor (VEGF) at both the mRNA and protein level. Knockdown of c-Jun expression and inhibition of JNK activation significantly blocked JSI-124 induced VEGF expression. Pretreatment with recombinant VEGF reduced JSI-124 induced apoptosis.</p> <p>Conclusions</p> <p>Taken together, our data demonstrates that JSI-124 activates the JNK signaling pathway independent of apoptosis and cell cycle arrest, leading to increased VEGF expression.</p

Potential of Van de Ven’s (2007) concept of engaged scholarship to enhance the sustainability and appropriateness of management consultancy and university knowledge exchange projects recommendations to challenge the widespread hype of newness (Smil, 2022)

This paper will outline some emerging thoughts on the potential applicability of Van de Ven’s Engaged Scholarship concept in consultancy and knowledge exchange projects. To structure this paper the questions posed at an event titled “Putting Engaged Scholarship to Work: Projects, Partners and Progress” hosted by Ram (2019 cited by Kapasi) at Aston University will be summarised. The original definition of Engaged Scholarship offered by Van de Ven (2007) is that it is “a participative form of research for obtaining the advice and perspectives of key stakeholders (researchers, users, clients, sponsors, and practitioners) to understand a complex social problem” The commentary will be illustrated by some wider evidence drawn from industry analysis, professional bodies and academic research on Organisational Transformation and Digital Transformation Projects. These sources are frequently conducted independently where concentration on individual technical, and often siloed, aspects of consultancy and knowledge exchange project recommendations do not address the necessary breadth of understanding to improve the sustainability of such projects and therefore challenge the hype (Smil, 2022) that is associated with complex and expensive societal challenge of the typically high failure rates of Organisational Transformation and Digital Transformation investments. It is proposed by Neal et al (2023) that role frequently referred to as “Brokers, intermediaries, and boundary spanners (BIBS)” can offer a “… bridge (to) research and policy or practice and can elevate the role of evidence in decision making” (op cit)