Oligodendrocytes make myelin and support axons metabolically with lactate. However, it is unknown how glucose utilization and glycolysis are adapted to the different axonal energy demands. Spiking axons release glutamate and oligodendrocytes express NMDA receptors of unknown function. Here we show that the stimulation of oligodendroglial NMDA receptors mobilizes glucose transporter GLUT1, leading to its incorporation into the myelin compartment in vivo. When myelinated optic nerves from conditional NMDA receptor mutants are challenged with transient oxygen-glucose deprivation, they show a reduced functional recovery when returned to oxygen-glucose but are indistinguishable from wild-type when provided with oxygen-lactate. Moreover, the functional integrity of isolated optic nerves, which are electrically silent, is extended by preincubation with NMDA, mimicking axonal activity, and shortened by NMDA receptor blockers. This reveals a novel aspect of neuronal energy metabolism in which activity-dependent glutamate release enhances oligodendroglial glucose uptake and glycolytic support of fast spiking axons.

Physiological processes such as protein folding and molecular recognition are intricately linked to their dynamic signature, which is reflected in their thermal coefficient. In addition, the local conformational entropy is directly related to the degrees of freedom, which each residue possesses within its conformational space. Therefore, the temperature dependence of the local conformational entropy may provide insight into understanding how local dynamics may affect the stability of proteins. Here, we analyze the temperature dependence of internal methyl group dynamics derived from the cross-correlated relaxation between dipolar couplings of two CH bonds within ubiquitin. Spanning a temperature range from 275 to 308 K, internal methyl group dynamics tend to increase with increasing temperature, which translates to a general increase in local conformational entropy. With this data measured over multiple temperatures, the thermal coefficient of the methyl group order parameter, the characteristic thermal coefficient, and the local heat capacity were obtained. By analyzing the distribution of methyl group thermal coefficients within ubiquitin, we found that the N-terminal region has relatively high thermostability. These results indicate that methyl groups contribute quite appreciably to the total heat capacity of ubiquitin through the regulation of local conformational entropy.

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Biological control systems regulate the behavior of biological systems in a constantly changing environment. Homeostasis is the most widely studied outcome of biological control systems. Homeostatic systems maintain the system in its desired state despite variations in system parameters or the externally-determined input rates of their constituents, i.e. they have zero or near zero steady state error. On the other hand, allostatic systems are not resistant against environmental changes and the steady state level of their controlled variables responds positively to the changes in their input rates. Little is known, however, on the existence and frequency of reverse allostatic systems, where the steady state value of the controlled variable correlates negatively with the input rate of that variable. In the present study, we derive the minimal conditions for the existence and local stability of reverse allostatic systems, and demonstrate in examples of metabolic, pharmacological, pathophysiological and ecological systems that the reverse allostasis requirements are relatively non-stringent and may be satisfied in biological systems more commonly than usually thought. The possible existence of reverse allostatic systems in nature and their counter-intuitive implications in physiological systems, drug treatment, ecosystem management, and biological control are explored and testable predictions are made.