The concept of the Myc (c-myc, n-myc, l-myc) oncogene as a canonical, DNA-bound transcription factor has consistently changed over the past few years. Indeed, Myc controls gene expression programs at multiple levels: directly binding chromatin and recruiting transcriptional coregulators; modulating the activity of RNA polymerases (RNAPs); and drawing chromatin topology. Therefore, it is evident that Myc deregulation in cancer is a dramatic event. Glioblastoma multiforme (GBM) is the most lethal, still incurable, brain cancer in adults, and it is characterized in most cases by Myc deregulation. Metabolic rewiring typically occurs in cancer cells, and GBM undergoes profound metabolic changes to supply increased energy demand. In nontransformed cells, Myc tightly controls metabolic pathways to maintain cellular homeostasis. Consistently, in Myc-overexpressing cancer cells, including GBM cells, these highly controlled metabolic routes are affected by enhanced Myc activity and show substantial alterations. On the other hand, deregulated cancer metabolism impacts Myc expression and function, placing Myc at the intersection between metabolic pathway activation and gene expression. In this review paper, we summarize the available information on GBM metabolism with a specific focus on the control of the Myc oncogene that, in turn, rules the activation of metabolic signals, ensuring GBM growth.

The deuterium (D) abundance of tree-ring cellulose archives past climatic conditions, but previous attempts to access this archive have led to conflicting results. Based on an overview of D fractionation mechanisms in plants, we explain why past measurements of D abundance yield unreliable paleo signals. Our data show that variation in D abundance among the C-H groups (isotopomer variation) of tree-ring cellulose is generally greater than variation in D abundance due to climatic influences. A comparison of the D isotopomer abundances of soluble sugars of annual plants and of trees, and of tree-ring cellulose shows that an "isotopomer pattern" of the C-3 photosynthetic pathway is transmitted from soluble sugars to tree-ring cellulose. Differences in this pattern between oaks and conifers appear to be related to differences in metabolism. Furthermore, the patterns are modified by hydrogen isotope exchange between C-H groups and source water during cellulose synthesis. Based on these results, we propose a strategy to simultaneously reconstruct climate signals and signals related to tree physiology from D isotopomers of tree rings. Combination of climate signals and physiological signals may allow the detection of century-time-scale adaptations of trees to past environmental change, and help to forecast future adaptations. (C) 2008 Elsevier B.V. All rights reserved.

Mitochondria are strongly involved in the production of reactive oxygen species, considered as the pathogenic agent of many diseases and of aging. The mitochondrial theory of aging considers somatic mutations of mitochondrial DNA induced by oxygen radicals as the primary cause of energy decline; experimentally, complex I appears to be mostly affected and to become strongly rate limiting for electron transfer. Mitochondrial bioenergetics is also deranged in human platelets upon aging, as shown by the decreased Pasteur effect (enhancement of lactate production by respiratory chain inhibition). Cells counteract oxidative stress by antioxidants; among lipophilic antioxidants, coenzyme Q is the only one of endogenous biosynthesis. Exogenous coenzyme Q, however, protects cells from oxidative stress by conversion into its reduced antioxidant form by cellular reductases. (C) 2000 Elsevier Science B.V. All rights reserved.