Glucocorticoids exert antiinflammatory, antiproliferative and immunosupressive effects. Paradoxically they may also enhance inflammation particularly in the nervous system, as shown in Cushing &... Show moreGlucocorticoids exert antiinflammatory, antiproliferative and immunosupressive effects. Paradoxically they may also enhance inflammation particularly in the nervous system, as shown in Cushing & PRIME; syndrome and neurodegenerative disorders of humans and models of human diseases. ."The Wobbler mouse model of amyotrophic lateral sclerosis shows hypercorticoidism and neuroinflammation which subsided by treatment with the glucocorticoid receptor (GR) modulator Dazucorilant (CORT113176). This effect suggests that GR mediates the chronic glucocorticoid unwanted effects. We now tested this hypothesis using a chronic stress model resembling the condition of the Wobbler mouse Male NFR/NFR mice remained as controls or were subjected to a restraining / rotation stress protocol for 3 weeks, with a group of stressed mice receiving CORT113176 also for 3 weeks. We determined the mRNAS or reactive protein for the proinflamatory factors HMGB1, TLR4, NFkB, TNF & alpha;, markers of astrogliosis (GFAP, SOX9 and acquaporin 4), of microgliosis (Iba, CD11b, P2RY12 purinergic receptor) as well as serum IL1 & beta; and corticosterone. We showed that chronic stress produced high levels of serum corticosterone and IL1 & beta;, decreased body and spleen weight, produced microgliosis and astrogliosis and increased proinflammatory mediators. In stressed mice, modulation of the GR with CORT113176 reduced Iba + microgliosis, CD11b and P2RY12 mRNAs, immunoreactive HMGB1 + cells, GFAP + astrogliosis, SOX9 and acquaporin expression and TLR4 and NFkB mRNAs vs. stress-only mice. The effects of CORT113176 indicate that glucocorticoids are probably involved in neuroinflammation. Thus, modulation of the GR would become useful to dampen the inflammatory component of neurodegenerative disorders. Show less
Artefacts made from stones, bones and teeth are fundamental to our understanding of human subsistence strategies, behaviour and culture in the Pleistocene. Although these resources are plentiful,... Show moreArtefacts made from stones, bones and teeth are fundamental to our understanding of human subsistence strategies, behaviour and culture in the Pleistocene. Although these resources are plentiful, it is impossible to associate artefacts to specific human individuals(1) who can be morphologically or genetically characterized, unless they are found within burials, which are rare in this time period. Thus, our ability to discern the societal roles of Pleistocene individuals based on their biological sex or genetic ancestry is limited(2-5). Here we report the development of a non-destructive method for the gradual release of DNA trapped in ancient bone and tooth artefacts. Application of the method to an Upper Palaeolithic deer tooth pendant from Denisova Cave, Russia, resulted in the recovery of ancient human and deer mitochondrial genomes, which allowed us to estimate the age of the pendant at approximately 19,000-25,000 years. Nuclear DNA analysis identifies the presumed maker or wearer of the pendant as a female individual with strong genetic affinities to a group of Ancient North Eurasian individuals who lived around the same time but were previously found only further east in Siberia. Our work redefines how cultural and genetic records can be linked in prehistoric archaeology. Show less
Palma-Bifani, P.; Chauvin, G.; Bonnefoy, M.; Rojo, P.M.; Petrus, S.; Rodet, L.; ... ; Zhang, Y. 2023
Buckner and Carroll [Trends in Cognitive Sciences (2007), Vol. 11, pp. 49–57] argued that episodic memory (EM), episodic future think- ing (EFT), theory of mind (ToM), and spatial navigation all... Show moreBuckner and Carroll [Trends in Cognitive Sciences (2007), Vol. 11, pp. 49–57] argued that episodic memory (EM), episodic future think- ing (EFT), theory of mind (ToM), and spatial navigation all build on the same mental mechanism—self-projection, that is, the ability to disengage from the immediate present and shift perspective to alternative temporal, mental, or spatial situations. Developmental studies indeed show that all four abilities undergo profound developmental changes around 4 years of age, and there are first indications of developmental interrelations between some of the abilities. However, strong evidence for the self-projection account, namely that all four abilities are interrelated in their emergence during early childhood, is still lacking. To thoroughly investigate the self-projection hypothesis, we tested 151 4-year-old children on 12 different tasks assessing their EM, EFT, ToM, and spatial navigation skills (3 tasks per ability). Structural equation modeling under maximum likelihood estimation was conducted on a final sample of 144 children to evaluate a model with the 12 tasks as indicators and self-projection as the latent factor. The model showed a very good fit to the data. However, the factor loadings, indicating the strength of association between the latent factor and the indicators, were very low—which speaks against the validity of the measurement model. In summary, the results do not support the assumption of a common latent factor underlying the various abilities EM, EFT, ToM, and spatial navigation. Implications of our results for the self-projection account and possible related theoretical and methodological challenges are discussed. Show less
Brandl, B.R.; Bettonvil, F.C.M.; Van Boekel, R.; Glauser, A.; Quanz, S.P.; Absil, O.; ... ; Siebenmorgen, R. 2022
