Molecular Dynamics and Metadynamics Insights of 1,4-Dioxane-Induced Structural Changes of Biomembrane Models.

1,4-Dioxane is a cytotoxic B2-type human carcinogen, a serious water pollutant produced solely by industrial activity. The effect of 1,4-dioxane on phospholipid membrane models composed of dipalmitoyl-phosphatidylcholine (DPPC) and its branched isomer (isodipalmitoyl-phosphatidylcholine, IPPC) was investigated using MD simulations. Clear and polluted membranes were compared by membrane parameters such as area per lipid (APL), volume per lipid (VPL), compressibility modulus, membrane thickness, and orderliness of lipid tails. While neat systems significantly differ from each other, the presence of the pollutant has the same effect on both types of lipid membranes. High density of dioxane appears in the vicinity of ester groups, which pushes away lipid headgroups from each other, leading to an overall change in lipid structure: APL and VPL grows, while the orderliness of lipid tails, membrane thickness, and compressibility modulus decrease. Orientational preferences of water and dioxane molecules were also investigated and different membrane regions have been specified according to the stance of water molecules. Free-energy profile for 1,4-dioxane penetration mechanism into DPPC membranes was carried out using metadynamics for two different concentrations of the pollutant (c1 = 7.51 g/dm3, c2 = 75.10 g/dm3), which showed that the higher the concentration is, the lower the free energy of penetration gets. Only a small free-energy barrier was found in the headgroup region and accumulation of dioxane is thermodynamically unfavored in the middle of the bilayer. The penetration mechanism has been described in detail based on the orientational preference of 1,4-dioxane molecules and the free-energy profiles.

Hyperostosis frontalis interna in ancient populations from the Carpathian Basin - A possible relationship between lifestyle and risk of development.

OBJECTIVE: The prevalence of hyperostosis frontalis interna (HFI) was examined in different periods of the Carpathian Basin from 4900 BCE to 17th century AD. The study seeks to evaluate temporal changes in HFI and the possible impact of lifestyle on it. MATERIALS: The studied material consisted of 4668 crania from Hungary and Serbia. METHODS: The crania were analyzed employing macroscopic and endoscopic examination. RESULTS: In historic periods, sex and age played a pivotal role in HFI development. Among predominantly pastoralist populations of the 5th-8th and 10th centuries, prevalence of HFI was considerably higher than in the medieval populations of the 9th-17th centuries. CONCLUSIONS: In addition to age and sex, other factors could be implicated in HFI development. The physiological effects of the pastoralist lifestyle and diet on insulin regulation could explain the increased risk of developing HFI in the 5th-8th and 10th-century populations. SIGNIFICANCE: The study provides the first comprehensive dataset of HFI from different archaeological periods from the Carpathian Basin. It has implications for lifestyle and risk of HFI development in past populations. LIMITATIONS: The archaeological periods are not equally represented. SUGGESTIONS FOR FURTHER RESEARCH: In order to better understand the etiology of HFI, lifestyle factors can be used to elucidate the risk of developing HFI in ancient populations.