Early human occupation of Western Europe: Paleomagnetic dates for two paleolithic sites in Spain

The lacustrine deposits infilling the intramontane Guadix-Baza Basin, in the Betic Range of Southern Spain, have yielded abundant well-preserved lithic artifacts. In addition, the lake beds contain a wide range of micromammals including Mimomys savini and Allophaiomys burgondiae and large mammals such as Mammuthus and Hippopotamus together with the African saber-toothed felid Megantereon. The association of the lithic artifacts along with the fossil assemblages, themselves of prime significance in the Eurasian mammal biochronology, is providing new insight into the controversy of the human settlement in Southern Europe. Despite the importance of the artifacts and fossil assemblage, estimates of the geological age of the site are still in conflict. Some attempts at dating the sediments have included biochronology, uranium series, amino acid racemization, and stratigraphic correlation with other well-dated sections in the basin, but so far have failed to yield unambiguous ages. Here we present paleomagnetic age dating at the relevant localities and thus provide useful age constraints for this critical paleoanthropological and mammal site. Our data provide firm evidence for human occupation in Southern Europe in the Lower Pleistocene, around 1 mega-annum ago. The current view of when and how hominids first dispersed into Europe needs to be reevaluated.

A new strategy to decrease N-methyl-d-aspartate (NMDA) receptor coactivation: Inhibition of d-serine synthesis by converting serine racemase into an eliminase

Serine racemase is a brain-enriched enzyme that synthesizes d-serine, an endogenous modulator of the glycine site of N-methyl-d-aspartate (NMDA) receptors. We now report that serine racemase catalyzes an elimination reaction toward a nonphysiological substrate that provides a powerful tool to study its neurobiological role and will be useful to develop selective enzyme inhibitors. Serine racemase catalyzes robust elimination of l-serine O-sulfate that is 500 times faster than the physiological racemization reaction, generating sulfate, ammonia, and pyruvate. This reaction provides the most simple and sensitive assay to detect the enzyme activity so far. We establish stable cell lines expressing serine racemase and show that serine racemase can also be converted into a powerful eliminase in cultured cells, while the racemization of l-serine is inhibited. Likewise, l-serine O-sulfate inhibits the synthesis of d-serine in primary astrocyte cultures. We conclude that the synthetic compound l-serine O-sulfate is a better substrate than l-serine as well as an inhibitor of d-serine synthesis. Inhibition of serine racemase provides a new strategy to selectively decrease NMDA receptor coactivation and may be useful in conditions in which overstimulation of NMDA receptors plays a pathological role.