To our knowledge, this is the first demonstration of downregulation of LDHA in cancer. Although unexpected findings, silencing of LDHA and downregulation of several other glycolysis essential genes raise the intriguing possibility that IDH(mt) gliomas have limited glycolytic capacity, which may contribute to their slow growth and better prognosis.

cBefore the Earth's complete oxygenation (0.58 to 0.55 billion years [Ga] ago), the photic zone of the Proterozoic oceans was probably redox stratified, with a slightly aerobic, nutrient-limited upper layer above a light-limited layer that tended toward euxinia. In such oceans, cyanobacteria capable of both oxygenic and sulfide-driven anoxygenic photosynthesis played a fundamental role in the global carbon, oxygen, and sulfur cycle. We have isolated a cyanobacterium, Pseudanabaena strain FS39, in which this versatility is still conserved, and we show that the transition between the two photosynthetic modes follows a surprisingly simple kinetic regulation controlled by this organism's affinity for H 2 S. Specifically, oxygenic photosynthesis is performed in addition to anoxygenic photosynthesis only when H 2 S becomes limiting and its concentration decreases below a threshold that increases predictably with the available ambient light. The carbon-based growth rates during oxygenic and anoxygenic photosynthesis were similar. However, Pseudanabaena FS39 additionally assimilated NO 3 ؊ during anoxygenic photosynthesis. Thus, the transition between anoxygenic and oxygenic photosynthesis was accompanied by a shift of the C/N ratio of the total bulk biomass. These mechanisms offer new insights into the way in which, despite nutrient limitation in the oxic photic zone in the mid-Proterozoic oceans, versatile cyanobacteria might have promoted oxygenic photosynthesis and total primary productivity, a key step that enabled the complete oxygenation of our planet and the subsequent diversification of life.O xygenic photosynthesis (oxygenic P) couples the power of two photosystems (photosystem I [PSI] and PSII) for the extraction of electrons from water (equation 1) to reduce CO 2 .Nowadays, this metabolism drives the major part of Earth=s ecosystems by providing its products, oxygen and organic carbon, to other organisms. However, oxygenic P has not always been the dominant photosynthetic process. From its evolution, which began possibly more than 3 billion years (Ga) ago (1), until its final success in oxygenating the atmosphere and biosphere (0.58 to 0.55 Ga ago), oxygenic P always had to compete with anoxygenic P, which uses alternative reduced electron donors, such as hydrogen sulfide (equation 2) (2):Intriguingly, cyanobacteria could have made a major contribution to primary productivity by both oxygenic P and anoxygenic P for billions of years (2), and this photosynthetic versatility was probably the key to their success in a reduced world. The balance between oxygenic P and anoxygenic P was probably dependent on environmental conditions, e.g., the light, nutrient, and H 2 S gradients. An understanding of how and why the global balance between oxygenic and anoxygenic P has changed on a geological time scale is therefore tightly connected to understanding of (i) the regulation of the switch between the two photosynthetic modes, which is dependent on relevant environmental conditions, and (ii) the C-and N-based growth ra...