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PURPOSE: Mutant isocitrate dehydrogenase 1 (mIDH1) alters the epigenetic regulation of chromatin, leading to a hypermethylation phenotype in adult glioma. This work focuses on identifying gene targets epigenetically dysregulated by mIDH1 to confer therapeutic resistance to ionizing radiation (IR). EXPERIMENTAL DESIGN: We evaluated changes in the transcriptome and epigenome in a radioresistant mIDH1 patient-derived glioma cell culture (GCC) following treatment with an mIDH1-specific inhibitor, AGI-5198. We identified Zinc Finger MYND-Type Containing 8 (ZMYND8) as a potential target of mIDH1 reprogramming. We suppressed ZMYND8 expression by shRNA knockdown and genetic knockout (KO) in mIDH1 glioma cells and then assessed cellular viability to IR. We assessed the sensitivity of mIDH1 GCCS to pharmacologic inhibition of ZMYND8-interacting partners: HDAC, BRD4, and PARP. RESULTS: Inhibition of mIDH1 leads to an upregulation of gene networks involved in replication stress. We found that the expression of ZMYND8, a regulator of DNA damage response, was decreased in three patient-derived mIDH1 GCCs after treatment with AGI-5198. Knockdown of ZMYND8 expression sensitized mIDH1 GCCs to radiotherapy marked by decreased cellular viability. Following IR, mIDH1 glioma cells with ZMYND8 KO exhibit significant phosphorylation of ATM and sustained γH2AX activation. ZMYND8 KO mIDH1 GCCs were further responsive to IR when treated with either BRD4 or HDAC inhibitors. PARP inhibition further enhanced the efficacy of radiotherapy in ZMYND8 KO mIDH1 glioma cells. CONCLUSIONS: These findings indicate the impact of ZMYND8 in the maintenance of genomic integrity and repair of IR-induced DNA damage in mIDH1 glioma. See related commentary by Sachdev et al., p. 1648.

In this paper, the gamma and neutron shielding behavior of chemically bonded high atomic number (Z), tungsten trioxide‐polyvinyl alcohol‐polyvinylpyrrolidone (PW), and bismuth oxide‐polyvinyl alcohol‐polyvinylpyrrolidone (PB) composites were reported at varying thickness. The PW and PB composites were prepared through the dissolution technique rather than the commonly used dispersion technique. The gamma and neutron attenuation characteristics of the composites were studied using 22Na (0.511 and 1.274 MeV energy) and 252Cf (0–10 MeV energy) sources, respectively. The half value layer of PW and PB composite was found to be 61.22 ± 0.914 mm and 48.29 ± 1.52 mm and the linear attenuation coefficient was found to be 0.115 and 0.144 cm−1 at 0.511 MeV, respectively. Further, the experimental gamma‐ray attenuation results were validated theoretically using Phy‐X software and found to be well in agreement with the experimental data. Both the composites also showed similar neutron shielding behavior when compared to the commercially used high‐density polyethylene (HDPE). The developed composites possess good mechanical properties as they did not show any cracks or wrinkles after undergoing 5400 bending cycles during the flex test, showing their high durability of flexibility. Thus, these composites are found to be suitable for shielding both, the gamma‐rays and neutrons. [ABSTRACT FROM AUTHOR]

Ethylene oxide (EtO), although banned for use, is still being detected in foodstuffs that have been fumigated to eradicate pests during storage and transport. Residual levels over the European Union's (EU) maximum residue limit (MRL) pose severe health concerns. Recent detection of EtO and its by-product 2-chloroethanol (2-CE) at alarming levels have led to product recalls throughout the EU. Here, a simple, automated headspace (HS)-trap method for the simultaneous determination of EtO and its derivative 2-CE by gas chromatography-mass spectrometry (GC-MS) at the required MRL of ≤ 0.05 mg/kg has been implemented. Syringe-based HS combined with backflushed trapping technology provided enrichment of multiple extractions from the same sample vial (known as multi-step enrichment or MSE®) to increase sensitivity for EtO and 2-CE analysis by GC-MS using single-ion-monitoring (SIM) mode. Method detection limits (MDLs) of 0.00059 mg/kg and 0.00219 mg/kg for EtO and 2-CE, respectively, were obtained without the need for manual handling, solvent extraction or derivatization methods. Recoveries were shown to average (n = 5) at 98% and 107% for EtO and 2-CE, respectively, and the reproducibility was <10% for both compounds. [ABSTRACT FROM AUTHOR]

Intensive vegetable production using pesticides has biggest threat to growers and the consumers. In such instances the accumulation of pesticide residues is increased due to relatively short pre-harvest interval. Use of pesticides without knowing the label claim information increases the cost of production, increases the number of spray and labour cost, ultimately leading to decrease in farmers profitability. Hence, the adoption of pesticide as per label claim is very much essential. The level of residues should be below the maximum residue limit (MRL) at the time of harvest. Most of the detected pesticides in vegetables are not registered by Central Insecticide Board and Registration committee (CIBRC) for use on that specific vegetable which is the off label use of pesticides. Crops grouping is the development of a model that allows extrapolation of residue data from a few representative crops to many other crops in the same group. This allows establishment of residue tolerances for the entire group of crops based on the residue values from certain key crops that are similar. The acceptance of representative crop is a critical component of the savings from using the crop groups. IR-4's involvement with efforts to remove pesticide residues as a barrier for exports for US-grown specialty crops has been growing in importance over the last 20 years. By establishing a common MRL on a specialty crop from a particular crop protection product use, trade irritants between the two countries can be prevented before they have the potential to become a major problem for specialty crop growers on each side of the border. The U.S./Canadian specialty crop partnership has yielded valuable results for all the stakeholders involved. IR4 signed MOUs with Canada, New Zealand, Brazil, Costa Rica, and Colombia. This model is also much needed for India to regulate the pesticide label claims for numerous crops. [ABSTRACT FROM AUTHOR]

The heavy metal speciation analysis in sediments helps us understand and evaluate essential and unavoidable issues in terms of both health and environmental hazards imposed by these metals in our lives. Analyzing the total content of heavy metals enables us to understand only the quantity of the contaminants. To understand the different species or the chemical forms of heavy metals available in the sediments, we must study their speciation. Speciation studies help us determine their possible sources as well as their environmental stability in terms of availability to plants and other organisms. The heavy metals in this study were specified using four-stage sequential extraction, also known as the BCR technique. This study mainly highlights the quantification of metal contamination of Cu, Zn, Pb, Ni, Cd & Cr, and chemical forms as species in sediment samples collected from different Pune District, Maharashtra sites. Heavy metal contamination from the collected samples was analyzed with the use of flame atomic absorption spectrometry. This study indicated that Zn and Ni are among the most abundant metals in the sediment samples; however, Cu and Cd belong to the least abundant category. The oxidizable and residual forms (immobile and cannot be used by the organisms readily) appeared dominant for most heavy metals. Very significant differences were observed in the speciation of heavy metals from sample to sample, which was probably due to differences in water/soil composition and the agrochemicals like pesticides, weedicides, and fertilizers used in agricultural practices; the wastewater generated from different pharmaceuticals, chemical processing and manufacturing industries as well as the improper wastewater treatment methods. [ABSTRACT FROM AUTHOR]

With frequent RASFF notifications from the EU countries, the residue testing of ethylene oxide (EtO) and its metabolite 2-chloroethanol (2-CE) in food commodities has become essential to check their compliance with MRLs. This study, for the first time, aimed at establishing a dynamic headspace-GC-MS/MS method for the simultaneous determination of these two analytes in acetonitrile extracts of cumin, ashwagandha, chilli powder, turmeric powder, guar gum, locust bean gum, and ginger powder. The samples (4 g) were extracted using acetonitrile (10 mL). A dispersive-solid phase extraction cleanup step with primary secondary amine sorbent (50 mg/mL) reduced the interfering signal of (matrix-derived) acetaldehyde by >40% in chilli powder, ginger, turmeric, and guar gum. This cleanup was not required for sesame seeds. With high selectivity and sensitivity, the GC-MS/MS approach identified and quantified both compounds simultaneously. At the spiking levels of 0.01, 0.02, and 0.05 mg/kg, the recoveries and precision were satisfactory (70–120%, RSDs, ≤15%). The headspace method-performance was similar to liquid injections. The method provided reproducible results when evaluated by two different laboratories. The method provided high-precision results for incurred residue analysis. Given its efficiency, the validated method is anticipated to improve the effectiveness of monitoring of EtO residues in food commodities. [ABSTRACT FROM AUTHOR]