Contribution of the d-Serine-Dependent Pathway to the Cellular Mechanisms Underlying Cognitive Aging

An association between age-related memory impairments and changes in functional plasticity in the aging brain has been under intense study within the last decade. In this article, we show that an impaired activation of the strychnine-insensitive glycine site of N-methyl-d-aspartate receptors (NMDA-R) by its agonist d-serine contributes to deficits of synaptic plasticity in the hippocampus of memory-impaired aged rats. Supplementation with exogenous d-serine prevents the age-related deficits of isolated NMDA-R-dependent synaptic potentials as well as those of theta-burst-induced long-term potentiation and synaptic depotentiation. Endogenous levels of d-serine are reduced in the hippocampus with aging, that correlates with a weaker expression of serine racemase synthesizing the amino acid. On the contrary, the affinity of d-serine binding to NMDA-R is not affected by aging. These results point to a critical role for the d-serine-dependent pathway in the functional alterations of the brain underlying memory impairment and provide key information in the search for new therapeutic strategies for the treatment of memory deficits in the elderly

P16-37. HIV controllers with weak CD8+ T cell responses maintain a tight control of infection despite carrying infectious viruses

International audienc

The cerebellar transcriptome during postnatal development of the Ts1Cje mouse, a segmental trisomy model for Down syndrome

The central nervous system of persons with Down syndrome presents cytoarchitectural abnormalities that likely result from gene-dosage effects affecting the expression of key developmental genes. To test this hypothesis, we have investigated the transcriptome of the cerebellum of the Ts1Cje mouse model of Down syndrome during postnatal development using microarrays and quantitative PCR (qPCR). Genes present in three copies were consistently overexpressed, with a mean ratio relative to euploid of 1.52 as determined by qPCR. Out of 63 three-copy genes tested, only five, nine and seven genes had ratios >2 or <1.2 at postnatal days 0 (P0), P15 and P30, respectively. This gene-dosage effect was associated with a dysregulation of the expression of some two-copy genes. Out of 8258 genes examined, the Ts1Cje/euploid ratios differed significantly from 1.0 for 406 (80 and 154 with ratios above 1.5 and below 0.7, respectively), 333 (11 above 1.5 and 55 below 0.7) and 246 genes (59 above 1.5 and 69 below 0.7) at P0, P15 and P30, respectively. Among the two-copy genes differentially expressed in the trisomic cerebellum, six homeobox genes, two belonging to the Notch pathway, were severely repressed. Overall, at P0, transcripts involved in cell differentiation and development were over-represented among the dysregulated genes, suggesting that cell differentiation and migration might be more altered than cell proliferation. Finally, global gene profiling revealed that transcription in Ts1Cje mice is more affected by the developmental changes than by the trisomic state, and that there is no apparent detectable delay in the postnatal development of the cerebellum of Ts1Cje mic

The Late Middle Palaeolithic Occupation of Abri du Maras (Layer 1, Neronian, Southeast France): Integrating Lithic Analyses, ZooMS and Radiocarbon Dating to Reconstruct Neanderthal Hunting Behaviour

The exact strategies and technologies underlying Neanderthal hunting events remain open for debate with lithic points being sparse across the European Middle Palaeolithic. An exception is the Neronian entity in southeast France, defined by ventrally retouched Soyons points. This study contextualises one of the largest Neronian assemblages, layer 1 at Abri du Maras. Our lithic analyses focussed on attributes described as indicative of projectile use or hafting to contextualise the morphometric and technological characteristics of the pointed implements at an assemblage level. We found that retouched points were made on a variety of blank types (including Levallois, laminar and discoidal flaking techniques) and ventral retouch is present across different artefact types (including points, scrapers and denticulates). Next, these lithic data were compared to similar typo-technological data recorded on a sample from the recently excavated and well-contextualised point-rich layer 4.1 of Abri du Maras (MIS-3). Zooarchaeology by Mass Spectrometry (ZooMS) was applied to 280 faunal remains from layer 1 and indicated significant proportions of equids, bovids, cervids and reindeer. Carnivore remains and carnivore modifications are absent, while human bone surface modifications are present across a variety of species. Five bones had sufficient collagen for radiocarbon dating but returned dates younger than expected (ca. 41–31 ka cal BP). Finally, we place Abri du Maras layer 1 in its broader regional context and discuss its relation to other Neronian assemblages and more general problematics inherent to studying material from old excavations

A 41,500 year-old decorated ivory pendant from Stajnia Cave (Poland)

Evidence of mobiliary art and body augmentation are associated with the cultural innovations introduced by Homo sapiens at the beginning of the Upper Paleolithic. Here, we report the discovery of the oldest known human-modified punctate ornament, a decorated ivory pendant from the Paleolithic layers at Stajnia Cave in Poland. We describe the features of this unique piece, as well as the stratigraphic context and the details of its chronometric dating. The Stajnia Cave plate is a personal 'jewellery' object that was created 41,500 calendar years ago (directly radiocarbon dated). It is the oldest known of its kind in Eurasia and it establishes a new starting date for a tradition directly connected to the spread of modern Homo sapiens in Europe

Le Genévrier thurifère, espèce partagée au nord et au sud de la Méditerranée

Le 4e colloque sur le Genévrier thurifère (octobre 2011), a été l’occasion de partager les connaissances, les expériences et les avancées scientifiques sur cette espèce partagée au Sud et au Nord de la Méditerranée... Une approche pluridisciplinaire, des sciences humaines et sociales aux sciences biologiques… et médicales a permis de montrer les relations très fortes que cet arbre entretient, depuis des siècles, avec l’Homme, mais aussi la confrontation entre des préoccupations de gestion et des préoccupations de recherche plus fondamentales. Cet article est la synthèse du colloque

Initial Upper Palaeolithic humans in Europe had recent Neanderthal ancestry

Modern humans appeared in Europe by at least 45,000 years ago1–5, but the extent of their interactions with Neanderthals, who disappeared by about 40,000 years ago6, and their relationship to the broader expansion of modern humans outside Africa are poorly understood. Here we present genome-wide data from three individuals dated to between 45,930 and 42,580 years ago from Bacho Kiro Cave, Bulgaria1,2. They are the earliest Late Pleistocene modern humans known to have been recovered in Europe so far, and were found in association with an Initial Upper Palaeolithic artefact assemblage. Unlike two previously studied individuals of similar ages from Romania7 and Siberia8 who did not contribute detectably to later populations, these individuals are more closely related to present-day and ancient populations in East Asia and the Americas than to later west Eurasian populations. This indicates that they belonged to a modern human migration into Europe that was not previously known from the genetic record, and provides evidence that there was at least some continuity between the earliest modern humans in Europe and later people in Eurasia. Moreover, we find that all three individuals had Neanderthal ancestors a few generations back in their family history, confirming that the first European modern humans mixed with Neanderthals and suggesting that such mixing could have been common

The ecology, subsistence and diet of ~45,000-year-old Homo sapiens at Ilsenhöhle in Ranis, Germany

Recent excavations at Ranis (Germany) identified an early dispersal of Homo sapiens into the higher latitudes of Europe by 45,000 years ago. Here we integrate results from zooarchaeology, palaeoproteomics, sediment DNA and stable isotopes to characterize the ecology, subsistence and diet of these early H. sapiens. We assessed all bone remains (n = 1,754) from the 2016-2022 excavations through morphology (n = 1,218) or palaeoproteomics (zooarchaeology by mass spectrometry (n = 536) and species by proteome investigation (n = 212)). Dominant taxa include reindeer, cave bear, woolly rhinoceros and horse, indicating cold climatic conditions. Numerous carnivore modifications, alongside sparse cut-marked and burnt bones, illustrate a predominant use of the site by hibernating cave bears and denning hyaenas, coupled with a fluctuating human presence. Faunal diversity and high carnivore input were further supported by ancient mammalian DNA recovered from 26 sediment samples. Bulk collagen carbon and nitrogen stable isotope data from 52 animal and 10 human remains confirm a cold steppe/tundra setting and indicate a homogenous human diet based on large terrestrial mammals. This lower-density archaeological signature matches other Lincombian-Ranisian-Jerzmanowician sites and is best explained by expedient visits of short duration by small, mobile groups of pioneer H. sapiens. [Abstract copyright: © 2024. The Author(s).

Identifying the unidentified fauna enhances insights into hominin subsistence strategies during the Middle to Upper Palaeolithic transition

Understanding Palaeolithic hominin subsistence strategies requires the comprehensive taxonomic identification of faunal remains. The high fragmentation of Late Pleistocene faunal assemblages often prevents proper taxonomic identification based on bone morphology. It has been assumed that the morphologically unidentifiable component of the faunal assemblage would reflect the taxonomic abundances of the morphologically identified portion. In this study, we analyse three faunal datasets covering the Middle to Upper Palaeolithic transition (MUPT) at Bacho Kiro Cave (Bulgaria) and Les Cottés and La Ferrassie (France) with the application of collagen type I peptide mass fingerprinting (ZooMS). Our results emphasise that the fragmented component of Palaeolithic bone assemblages can differ significantly from the morphologically identifiable component. We obtain contrasting identification rates between taxa resulting in an overrepresentation of morphologically identified reindeer (Rangifer tarandus) and an underrepresentation of aurochs/bison (Bos/Bison) and horse/European ass (Equus) at Les Cottés and La Ferrassie. Together with an increase in the relative diversity of the faunal composition, these results have implications for the interpretation of subsistence strategies during a period of possible interaction between Neanderthals and Homo sapiens in Europe. Furthermore, shifts in faunal community composition and in carnivore activity suggest a change in the interaction between humans and carnivores across the MUPT and indicate a possible difference in site use between Neanderthals and Homo sapiens. The combined use of traditional and biomolecular methods allows (zoo)archaeologists to tackle some of the methodological limits commonly faced during the morphological assessment of Palaeolithic bone assemblages