NMR measurements on intercalated 3R-TaS2.Ix (I=NH3 and N2H4)

Proton nuclear magnetic resonance was used to probe the environment of the intercalant molecule in low dimensional (aeolotropic) solids 3RI-TaS2(NH3)2/3 and 3RII-TaS2(N2H4)4/3, and, specifically to look for phase transitions associated with changes in superlattice geometry. The proton resonance frequency for the intercalated molecules in the temperature interval 200 to 300K indicates that there are different magnetic environments in three temperature domains. (i) There is only one resonance field for molecules in isotropic magnetic environments. (ii) The high- and low-temperature domains (I and III) have molecules in only two different environments, whereas in the middle temperature domain (II) there are at least four different magnetic environments. (iii) The different magnetic environments measured by the ratio of anisotropic to isotropic resonance absorption intensity (rai) indicate that the ratios rai are constants of the sample in domains I and II. (iv) At low temperatures (domain III), rai depends on magnetic field polarisation effects and the temperature treatment of the sample. The authors conclude that the different magnetic environments observed for ammonia and hydrazine appear to be determined by the host, octahedrally coordinate TaS2

IDH1 mutations alter citric acid cycle metabolism and increase dependence on oxidative mitochondrial metabolism.

Oncogenic mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in several types of cancer, but the metabolic consequences of these genetic changes are not fully understood. In this study, we performed (13)C metabolic flux analysis on a panel of isogenic cell lines containing heterozygous IDH1/2 mutations. We observed that under hypoxic conditions, IDH1-mutant cells exhibited increased oxidative tricarboxylic acid metabolism along with decreased reductive glutamine metabolism, but not IDH2-mutant cells. However, selective inhibition of mutant IDH1 enzyme function could not reverse the defect in reductive carboxylation activity. Furthermore, this metabolic reprogramming increased the sensitivity of IDH1-mutant cells to hypoxia or electron transport chain inhibition in vitro. Lastly, IDH1-mutant cells also grew poorly as subcutaneous xenografts within a hypoxic in vivo microenvironment. Together, our results suggest therapeutic opportunities to exploit the metabolic vulnerabilities specific to IDH1 mutation

IDH1 Mutations Alter Citric Acid Cycle Metabolism and Increase Dependence on Oxidative Mitochondrial Metabolism

Oncogenic mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in several types of cancer, but the metabolic consequences of these genetic changes are not fully understood. In this study, we performed 13C metabolic flux analysis on a panel of isogenic cell lines containing heterozygous IDH1/2 mutations. We observed that under hypoxic conditions, IDH1-mutant cells exhibited increased oxidative tricarboxylic acid metabolism along with decreased reductive glutamine metabolism, but not IDH2-mutant cells. However, selective inhibition of mutant IDH1 enzyme function could not reverse the defect in reductive carboxylation activity. Furthermore, this metabolic reprogramming increased the sensitivity of IDH1-mutant cells to hypoxia or electron transport chain inhibition in vitro. Lastly, IDH1-mutant cells also grew poorly as subcutaneous xenografts within a hypoxic in vivo microenvironment. Together, our results suggest therapeutic opportunities to exploit the metabolic vulnerabilities specific to IDH1 mutation.National Institutes of Health (U.S.) (Grants R01CA168653 and 5-P30-CA14051-39)David H. Koch Institute for Integrative Cancer Research at MIT. DFHCC Bridge ProjectBurroughs Wellcome FundSmith Family FoundationVirginia and D.K. Ludwig Fund for Cancer ResearchDamon Runyon Cancer Research Foundatio