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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.

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]

A new database containing all available experimental and evaluated β-delayed neutron data is presented in this paper. The database is the product of an international effort coordinated by the International Atomic Energy Agency. It comprises a microscopic section including all available experimental data on beta-decay half-lives, β-delayed neutron emission probabilities and spectra, as well as new systematics and global theoretical calculations for comparison. The beta-delayed neutron data for individual precursors have been benchmarked against available data on macroscopic properties such as total delayed-neutron yields and spectra, delayed-neutron decay curves and time-dependent group parameters using the summation method. All available measured macroscopic data have also been compiled in the macroscopic section of the database. The dedicated database is available online on the IAEA server (URL:http://www-nds.iaea.org/beta-delayed-neutron/database.html).

OBJECTIVE: To describe the characteristics of compatible poliomyelitis cases and to assess the programmatic implications of clusters of such cases in India. METHODS: We described the characteristics of compatible poliomyelitis cases, identified clusters of compatible cases (two or more in the same district or neighbouring districts within two months), and examined their relationship to wild poliovirus cases. FINDINGS: There were 362 compatible cases in 2000. The incidence of compatible cases was higher in districts with laboratory-confirmed poliomyelitis cases than in districts without laboratory-confirmed cases. Of 580 districts, 96 reported one compatible case and 72 reported two or more compatible cases. Among these 168 districts with at least one compatible case, 123 had internal or cross- border clusters of compatible cases. In 27 districts with clusters of compatible cases, no wild poliovirus was isolated either in the same district or in neighbouring districts. Three of these 27 districts presented laboratory-confirmed poliomyelitis cases during 2001. CONCLUSION: Most clusters of compatible cases occurred in districts identified as areas with continuing wild poliovirus transmission and where mopping-up vaccination campaigns were carried out. As certification nears, areas with compatible poliomyelitis cases should be investigated and deficiencies in surveillance should be corrected in order to ensure that certification is justified.

OBJECTIVE: Vaccine-associated paralytic poliomyelitis (VAPP) is a rare but serious consequence of the administration of oral polio vaccine (OPV). Intensified OPV administration has reduced wild poliovirus transmission in India but VAPP is becoming a matter of concern. METHODS: We analysed acute flaccid paralysis (AFP) surveillance data in order to estimate the VAPP risk in this country. VAPP was defined as occurring in AFP cases with onset of paralysis in 1999, residual weakness 60 days after onset, and isolation of vaccine-related poliovirus. Recipient VAPP cases were a subset with onset of paralysis between 4 and 40 days after receipt of OPV. FINDINGS: A total of 181 AFP cases met the case definition. The following estimates of VAPP risk were made: overall risk, 1 case per 4.1 to 4.6 million OPV doses administered; recipient risk,1 case per 12.2 million; first-dose recipient risk, 1case per 2.8 million; and subsequent-dose recipient risk, 1 case per 13.9 million. CONCLUSION: On the basis of data from a highly sensitive surveillance system the estimated VAPP risk in India is evidently lower than that in other countries, notwithstanding the administration of multiple OPV doses to children in mass immunization campaigns.