Project description:This study reveals a novel mechanism linking social isolation to anxiety through a glucocorticoid (GC)-driven, ventral hippocampal (vHip)-specific iron-α-synuclein (α-Syn) axis. Social isolation activates glucocorticoid receptors (GRs) in vHip pyramidal neurons, which upregulate transferrin receptor 1 (TfR1) to promote iron accumulation. Elevated iron induces α-Syn overexpression, thereby enhancing presynaptic glutamate release and neuronal hyperexcitability in the vHip; this ultimately drives anxiety-like behaviors. Gain-of-function/loss-of-function experiments confirm that TfR1 and α-Syn are essential for this pathway, while intranasal iron chelation or α-Syn inhibition rescues both neural and behavioral abnormalities. These findings establish the GR-TfR1-α-Syn axis as a therapeutic target for social stress-related anxiety, which bridges metallobiology and psychiatric pathophysiology.
Project description:The identification of sex-specific peptides in human tooth enamel by nanoflow liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) represents a quantum leap for the study of childhood and social relations more generally. Determining sex-related differences in prehistoric child rearing and mortality has been hampered by the inability to determine the biological sex of juveniles. We conducted nanoLC-MS/MS to identify sex-specific peptides in the dental enamel of a child from a settlement pit of the Early Bronze Age settlement of Schleinbach, Austria (c. 1950–1850 BC). Four perimortal impression fractures on the skull of the 5–6-year-old child indicate an intentional killing, with a co-buried loom weight as possible murder weapon. Proteomic analysis, conducted for the first time on prehistoric teeth in Austria, determined the child’s sex as male. While we cannot conclusively decide whether the child became the victim of conflicts between village groups or was slain by members of his own community, we suggest that contextual evidence points to the latter. A possible trigger of violence were the follow-on effects of an uncontrolled middle ear infection revealed by the osteological analysis. The boy from Schleinbach highlights the potential for further investigation of gender-biased violence, infanticide and child murder based on the recently developed method of proteomic sex identification.
Project description:Paleofeces are an important source of information to study the evolution of dietary habits and human health. The UNESCO World Heritage region of Hallstatt-Dachstein/Salzkammergut is one of Europe’s oldest cultural and industrial landscapes; its underground salt mines dating back at least to the 14th century BC are one of the few archaeological sites where paleofeces are well preserved. The high salt concentrations and the constant annual temperature at around 8°C inside the isolated Hallstatt mines have perfectly preserved organic archaeological artefacts (e.g. paleofeces, clothing, mining tools) that provide unique insights into the daily life of a progressive community in Hallstatt. Here we subjected human paleofeces dated from the Bronze Age to early Modern Times to an in-depth microscopic, metagenomic and proteomic analysis. This allowed us to reconstruct the diet of the former population and gain insights into their ancient gut microbiome composition. Our dietary survey identified bran and glumes of different cereals as one of the most prevalent plant fragments. This highly fibrous, carbohydrate-rich diet was supplemented with proteins from broad beans and occasionally with fruits, nuts, or animal food. Linked to these traditional dietary habits all ancient miners up to the early Modern times have gut microbiome structures akin to modern non-Westernized individuals which may indicate a shift in the gut community composition of modern Westernized populations due to quite recent dietary and lifestyle changes. When we extended our microbial survey to fungi present in the paleofeces, we observed in one of the Iron Age samples a high abundance of Penicillium roqueforti and Saccharomyces cerevisiae DNA. Genome-wide analysis indicates that both fungi were involved in food fermentation and provide the first molecular evidence for blue cheese and beer consumption during Iron Age Europe.
