Comparative Toxicity Assessment Of Glyphosate And Two Commercial Formulations In The Planarian \u3cem\u3eDugesia japonica\u3c/em\u3e

Introduction: Glyphosate is a widely used, non-selective herbicide. Glyphosate and glyphosate-based herbicides (GBHs) are considered safe for non-target organisms and environmentally benign at currently allowed environmental exposure levels. However, their increased use in recent years has triggered questions about possible adverse outcomes due to low dose chronic exposure in animals and humans. While the toxicity of GBHs has primarily been attributed to glyphosate, other largely unstudied components of GBHs may be inherently toxic or could act synergistically with glyphosate. Thus, comparative studies of glyphosate and GBHs are needed to parse out their respective toxicity. Methods: We performed such a comparative screen using pure glyphosate and two popular GBHs at the same glyphosate acid equivalent concentrations in the freshwater planarian Dugesia japonica. This planarian has been shown to be a useful model for both ecotoxicology and neurotoxicity/developmental neurotoxicity studies. Effects on morphology and various behavioral readouts were obtained using an automated screening platform, with assessments on day 7 and day 12 of exposure. Adult and regenerating planarians were screened to allow for detection of developmentally selective effects. Results: Both GBHs were more toxic than pure glyphosate. While pure glyphosate induced lethality at 1 mM and no other effects, both GBHs induced lethality at 316 μM and sublethal behavioral effects starting at 31.6 μM in adult planarians. These data suggest that glyphosate alone is not responsible for the observed toxicity of the GBHs. Because these two GBHs also include other active ingredients, namely diquat dibromide and pelargonic acid, respectively, we tested whether these compounds were responsible for the observed effects. Screening of the equivalent concentrations of pure diquat dibromide and pure pelargonic acid revealed that the toxicity of either GBH could not be explained by the active ingredients alone. Discussion: Because all compounds induced toxicity at concentrations above allowed exposure levels, our data indicates that glyphosate/GBH exposure is not an ecotoxicological concern for D. japonica planarians. Developmentally selective effects were not observed for all compounds. Together, these data demonstrate the usefulness of high throughput screening in D. japonica planarians for assessing various types of toxicity, especially for comparative studies of several chemicals across different developmental stages

Whole Methylome Analysis by Ultra-Deep Sequencing Using Two-Base Encoding

Methylation, the addition of methyl groups to cytosine (C), plays an important role in the regulation of gene expression in both normal and dysfunctional cells. During bisulfite conversion and subsequent PCR amplification, unmethylated Cs are converted into thymine (T), while methylated Cs will not be converted. Sequencing of this bisulfite-treated DNA permits the detection of methylation at specific sites. Through the introduction of next-generation sequencing technologies (NGS) simultaneous analysis of methylation motifs in multiple regions provides the opportunity for hypothesis-free study of the entire methylome. Here we present a whole methylome sequencing study that compares two different bisulfite conversion methods (in solution versus in gel), utilizing the high throughput of the SOLiD™ System. Advantages and disadvantages of the two different bisulfite conversion methods for constructing sequencing libraries are discussed. Furthermore, the application of the SOLiD™ bisulfite sequencing to larger and more complex genomes is shown with preliminary in silico created bisulfite converted reads

Impact Assessment of Biomass Burning on Air Quality in Southeast and East Asia During BASE-ASIA

A synergy of numerical simulation, ground-based measurement and satellite observation was applied to evaluate the impact of biomass burning originating from Southeast Asia (SE Asia) within the framework of NASA's 2006 Biomass burning Aerosols in Southeast Asia: Smoke Impact Assessment (BASE-ASIA). Biomass burning emissions in the spring of 2006 peaked in MarcheApril when most intense biomass burning occurred in Myanmar, northern Thailand, Laos, and parts of Vietnam and Cambodia. Model performances were reasonably validated by comparing to both satellite and ground-based observations despite overestimation or underestimation occurring in specific regions due to high uncertainties of biomass burning emission. Chemical tracers of particulate K(+), OC concentrations, and OC/EC ratios showed distinct regional characteristics, suggesting biomass burning and local emission dominated the aerosol chemistry. CMAQ modeled aerosol chemical components were underestimated at most circumstances and the converted AOD values from CMAQ were biased low at about a factor of 2, probably due to the underestimation of biomass emissions. Scenario simulation indicated that the impact of biomass burning to the downwind regions spread over a large area via the Asian spring monsoon, which included Southern China, South China Sea, and Taiwan Strait. Comparison of AERONET aerosol optical properties with simulation at multi-sites clearly demonstrated the biomass burning impact via longrange transport. In the source region, the contribution from biomass burning to AOD was estimated to be over 56%. While in the downwind regions, the contribution was still significant within the range of 26%-62%

Down regulation of acrolein on corticosterone secretion in male rats

Acrolein is a small unsaturated aldehyde and can be found in a wide range of resources including all types of smoke and exhaust gases from gasoline engines. Although the toxicity and damage of acrolein have been recognized, the action mechanisms of acrolein, especially that of acrolein on the response of stresshormones are still unclear. The present study hypothesized that administration of acrolein altered the secretion of both adrenocorticotropin (ACTH) and corticosterone via the regulation of steroid biosynthetic pathway in rat zona fasciculata-reticularis (ZFR) cells. Both in vivo and in vitro approaches were uased. In the in vivo study, intraperitonal injection of acrolein (2 mg/ml/kg) once daily for 1 or 3 days resulted in a reduction of plasma levels of ACTH and corticosterone as well as the intracellular cAMP and ACTH-induced secretion of corticosterone. The protein expression of ACTH receptor (ACTHR) in rat ZFR cells was also reduced by 40-60% after treatment of acrolein for 1 day and 3 days, respectively. In the in vitro study, rat ZFR cells were prepared and chanllenged with ACTH (10-9 M), forskolin (an adenylyl cyclase activitior, 10-5 M), 8-Br-cAMP (a permeable synthetic cAMP, 5x10-5 M), 25-OH-cholesterol (10-5 M) ± trilostane (an inhibitor of 3?-hydroxysteroid dehydrogenase, 3?-HSD, 10-5 M). The evoked release of corticosterone by ACTH, forskolin, 8-Br-cAMP and the induced release of pregnenolone in response to 25-OH-cholesterol plus triolostane were decreased. Since the accumulation of pregnenolone after blocking 3?-HSD by trilostane represents the activity of P450scc, therate-limiting step of steroid biosynthesis, we suggest that not only the cAMP pathway was inhibited, but also the enzyme activity of P450scc was attenuated following administration of acrolein. Although insignificant, the protein expression of steroidogenic acute regulatory protein (StAR) was decreased by 40% in ZFR cells after treatment of acrolein in vivo. Incubation of ZFR cells with acrolein (10-9~10-7 M) also decreased the in vitro release of corticosterone. These results suggest that administration of acrolein inhibited corticosterone production via the attenuation of cAMP pathway, StAR protein expression, and the enzyme activity of P450scc. The attenuation of protein expression of ACTHR (also named melanocortin 2 receptor, MC2R) and reduced secrection of ACTH indicated that the hypothalamus-pituitary-adrenal (H-P-A) axis was also down- regulated by the administration of acrolein

Beyond Blackboards: Engaging Underserved Middle School Students in Engineering

Beyond Blackboards is an inquiry-centered, after-school program designed to enhance middle school students’ engagement with engineering through design-based experiences focused on the 21st Century Engineering Challenges. Set within a predominantly lowincome, majority-minority community, our study aims to investigate the impact of Beyond Blackboards on students’ interest in and understanding of engineering, as well as their ability to align their educational and career plans. We compare participants’ and nonparticipants’ questionnaire responses before the implementation and at the end of the program’s first academic year. Statistically significant findings indicate a school-wide increase in students’ interest in engineering careers, supporting a shift in school culture. However, only program participants showed increased enjoyment of design-based strategies, understanding of what engineers do, and awareness of the steps for preparing for an engineering career. These quantitative findings are supported by qualitative evidence from participant focus groups highlighting the importance of mentors in shaping students’ awareness of opportunities within engineering

Signal transducer and activator of transcription 3 activation is associated with bladder cancer cell growth and survival

<p>Abstract</p> <p>Background</p> <p>Constitutive activation of signal transducer and activator of transcription 3 (Stat3) signaling pathway plays an important role in several human cancers. Activation of Stat3 is dependent on the phosphorylation at the tyrosine residue 705 by upstream kinases and subsequent nuclear translocation after dimerization. It remains unclear whether oncogenic Stat3 signaling pathway is involved in the oncogenesis of bladder cancer.</p> <p>Results</p> <p>We found that elevated Stat3 phosphorylation in 19 of 100 (19%) bladder cancer tissues as well as bladder cancer cell lines, WH, UMUC-3 and 253J. To explore whether Stat3 activation is associated with cell growth and survival of bladder cancer, we targeted the Stat3 signaling pathway in bladder cancer cells using an adenovirus-mediated dominant-negative Stat3 (Y705F) and a small molecule compound, STA-21. Both prohibited cell growth and induction of apoptosis in these bladder cancer cell lines but not in normal bladder smooth muscle cell (BdSMC). The survival inhibition might be mediated through apoptotic caspase 3, 8 and 9 pathways. Moreover, down-regulation of anti-apoptotic genes (Bcl-2, Bcl-xL and survivin) and a cell cycle regulating gene (cyclin D1) was associated with the cell growth inhibition and apoptosis.</p> <p>Conclusion</p> <p>These results indicated that activation of Stat3 is crucial for bladder cancer cell growth and survival. Therefore, interference of Stat3 signaling pathway emerges as a potential therapeutic approach for bladder cancer.</p