Fructose-driven glycolysis supports anoxia resistance in the naked mole-rat

The African naked mole-rat’s ($\textit{Heterocephalus glaber}$) social and subterranean lifestyle generates a hypoxic niche. Under experimental conditions, naked mole-rats tolerate hours of extreme hypoxia and survive 18 minutes of total oxygen deprivation (anoxia) without apparent injury. During anoxia, the naked mole-rat switches to anaerobic metabolism fueled by fructose, which is actively accumulated and metabolized to lactate in the brain. Global expression of the GLUT5 fructose transporter and high levels of ketohexokinase were identified as molecular signatures of fructose metabolism. Fructose-driven glycolytic respiration in naked mole-rat tissues avoids feedback inhibition of glycolysis via phosphofructokinase, supporting viability. The metabolic rewiring of glycolysis can circumvent the normally lethal effects of oxygen deprivation, a mechanism that could be harnessed to minimize hypoxic damage in human disease.Work was supported aEuropean Research Council (294678), the Deutsche Forschungsgemeinschaft SFB 665 and Go865/9-1, NSF (grant #0744979 ), NIH (grants HL71626 and HL606

Dimension characterizations of complexity classes

We use derandomization to show that sequences of positive pspace-dimension – in fact, even positive ∆ p k-dimension for suitable k – have, for many purposes, the full power of random oracles. For example, we show that, if S is any binary sequence whose ∆ p 3-dimension is positive, then BPP ⊆ PS and, moreover, every BPP promise problem is PS-separable. We prove analogous results at higher levels of the polynomial-time hierarchy. The dimension-almost-class of a complexity class C, denoted by dimalmost-C, is the class consisting of all problems A such that A ∈ CS for all but a Hausdorff dimension 0 set of oracles S. Our results yield several characterizations of complexity classes, such as BPP = dimalmost-P, Promise-BPP = dimalmost-P-Sep, and AM = dimalmost-NP, that refine previously known results on almost-classes.