The nature and chronology of human occupation at the Galerías Bajas, from Cueva de Ardales, Malaga, Spain.

The Cueva de Ardales is a hugely important Palaeolithic site in the south of the Iberian Peninsula owing to its rich inventory of rock art. From 2011-2018, excavations were carried out in the cave for the first time ever by a Spanish-German research team. The excavation focused on the entrance area of the cave, where the largest assemblage of non-figurative red paintings in the cave is found. A series of 50 AMS dates from the excavations prove a long, albeit discontinuous, occupation history spanning from the Middle Palaeolithic to the Neolithic. The dating of the Middle Palaeolithic layers agrees with the U/Th dating of some red non-figurative paintings in the entrance area. In addition, a large assemblage of ochre lumps was discovered in the Middle Palaeolithic layers. Human visits of the cave in the Gravettian and Solutrean can be recognized, but evidence from the Aurignacian and Magdalenian cannot be confirmed with certainty. The quantity and nature of materials found during the excavations indicate that Cueva de Ardales was not a campsite, but was mainly visited to carry out non-domestic tasks, such as the production of rock art or the burial of the dead.

Neovascularization and functional recovery after intracerebral hemorrhage is conditioned by the Tp53 Arg72Pro single-nucleotide polymorphism.

Intracerebral hemorrhage (ICH) is a devastating subtype of stroke that lacks effective therapy and reliable prognosis. Neovascularization following ICH is an essential compensatory response that mediates brain repair and modulates the clinical outcome of stroke patients. However, the mechanism that dictates this process is unknown. Bone marrow-derived endothelial progenitor cells (EPCs) promote endothelial repair and contribute to ischemia-induced neovascularization. The human Tp53 gene harbors a common single-nucleotide polymorphism (SNP) at codon 72, which yields an arginine-to-proline amino-acidic substitution (Arg72Pro) that modulates the apoptotic activity of the p53 protein. Previously, we found that this SNP controls neuronal susceptibility to ischemia-induced apoptosis in vitro. Here, we evaluated the impact of the Tp53 Arg72Pro SNP on vascular repair and functional recovery after ICH. We first analyzed EPC mobilization and functional outcome based on the modified Rankin scale scores in a hospital-based cohort of 78 patients with non-traumatic ICH. Patients harboring the Pro allele of the Tp53 Arg72Pro SNP showed higher levels of circulating EPC-containing CD34+ cells, EPC-mobilizing cytokines - vascular endothelial growth factor and stromal cell-derived factor-1α - and good functional outcome following ICH, when compared with the homozygous Arg allele patients, which is compatible with increased neovascularization. To assess directly whether Tp53 Arg72Pro SNP regulated neovascularization after ICH, we used the humanized Tp53 Arg72Pro knock-in mice, which were subjected to the collagenase-induced ICH. The brain endothelial cells of the Pro allele-carrying mice were highly resistant to ICH-mediated apoptosis, which facilitated cytokine-mediated EPC mobilization, cerebrovascular repair and functional recovery. However, these processes were not observed in the Arg allele-carrying mice. These results reveal that the Tp53 Arg72Pro SNP determines neovascularization, brain repair and neurological recovery after ICH. This study is the first in which the Pro allele of Tp53 is linked to vascular repair and ability to functionally recover from stroke.