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

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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

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

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

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, defned 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 faking techniques) and ventral retouch is present across diferent 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 signifcant proportions of equids, bovids, cervids and reindeer. Carnivore remains and carnivore modifcations are absent, while human bone surface modifcations are present across a variety of species. Five bones had sufcient 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

Combining collagen extraction with mineral Zn isotope analyses from a single sample for robust palaeoecological investigations

Collagen extraction from bones or dentine, commonly used for radiocarbon (14C) dating and stable carbon and nitrogen isotope (δ13C and δ15N) analyses, involves the dissolution of the bioapatite of skeletal elements. This fraction is typically disposed of during pretreatment. Here, we test the possibility of utilising this dissolved mineral solution for analysis of the bioapatite zinc isotope composition (δ66Zn). Bioapatite δ66Zn is a novel trophic level indicator similar to collagen δ15N but with isotopic fractionation independent from nitrogen, thus providing additional dietary information. We tested ways to minimise Zn contamination of the dissolved mineral phase during collagen extraction. We then used archaeological bone samples from Ain Difla (Jordan) and Ranis (Germany) to compare δ66Zn values of dissolved bioapatite following our collagen extraction protocol with δ66Zn values from the same sample material dissolved in a metal-free cleanroom. Our results demonstrate that with only minor adjustments to minimise Zn contamination, the dissolved mineral solution from collagen extraction protocols commonly employed for 14C dating and (palaeo)dietary analysis can be used for additional δ66Zn analyses even when collagen extraction does not take place in a cleanroom. Our protocol allows us to gain an additional dietary proxy to complement δ15N trophic level interpretations and perform more robust (palaeo)ecological investigations without further destructive sampling