Cultural inter-population differences do not reflect biological distances: an example of interdisciplinary analysis of populations from Eastern Adriatic coast.

AIM: To compare the population group from the Sopot graveyard with population groups from traditional Croatian medieval graveyards by using anthropological, craniometrics, and mitochondrial (mtDNA) analysis and to examine if the cultural differences between population groups reflect biological differences. METHODS: We determined sex, age at death, pathological, and traumatic changes of skeletal remains from the Sopot graveyard and compared them with a cumulative medieval sample from the same region. We also performed principal component analysis to compare skeletal remains from Sopot with those from Ostrovica and other Central European samples according to 8 cranial measurements. Finally, we compared 46 skeletons from Sopot with medieval (Ostrovica) and contemporary populations using mDNA haplogroup profiling. RESULTS: The remains from Sopot were similar to the cumulative sample in lifestyle and quality of life markers. Principal component analysis showed that they were closely related to Eastern Adriatic coast sites (including Ostrovica and Sopot) in terms of cranial morphology, indicating similar biological makeup. According to mDNA testing, Sopot population showed no significant differences in the haplogroup prevalence from either medieval or contemporary populations. CONCLUSION: This study shows that the Sopot population does not significantly differ from other medieval populations from this area. Besides similar quality of life markers, these populations also had similar biological markers. Substantial archeological differences can therefore be attributed to apparent cultural influences, which in this case do not reflect biological differences.

Myricetin Inhibits Islet Amyloid Polypeptide (IAPP) Aggregation and Rescues Living Mammalian Cells from IAPP Toxicity.

The aggregation of the amyloidogenic polypeptide IAPP (Islet Amyloid Polypeptide, amylin) is believed to play a direct role in the death of pancreatic ß-islet cells in type II diabetes. Preventing the initial aggregation event of IAPP is one strategy for slowing, and possibly preventing, the progression of this disease. Here, we investigate myricetin's potential as an inhibitor of IAPP aggregation. We show that myricetin prevented thioflavin T binding in a concentration dependent manner. Atomic force microscopy revealed that myricetin prevented fiber formation under rigorous conditions conducive to forming IAPP aggregates. Using an IAPP-EGFP (Enhanced Green Fluorescent Protein) protein construct, we find that high concentrations of myricetin slowed the in vivo aggregation of IAPP-EGFP. Myricetin was also found to rescue living mammalian cells from the toxic effects of IAPP. These results indicate that myricetin is a strong inhibitor of IAPP amyloid aggregation and a potential lead molecule for the development of an amyloid inhibiting therapeutic.

Selection for nonamyloidogenic mutants of islet amyloid polypeptide (IAPP) identifies an extended region for amyloidogenicity.

The aggregation of the 37-residue protein, islet amyloid polypeptide (IAPP), as either insoluble amyloid or as small oligomers, appears to play a direct role in the death of pancreatic beta-islet cells in type II diabetes. While IAPP has been known to be the primary component of type II diabetes amyloid, the molecular interactions responsible for this aggregation have not been identified. To identify the aggregation-prone region(s), we constructed a library of randomly generated point mutants of IAPP. This mutant IAPP library was expressed in Escherichia coli as genetic fusions to the reporter protein enhanced green fluorescent protein (EGFP). Because IAPP aggregates rapidly, both independently and when fused to EGFP, the fusion protein does not yield a functional, fluorescent EGFP. However, mutations of IAPP that result in nonamyloidogenic sequences remain soluble and allow EGFP to fold and fluoresce. Using this screen, we identified 22 single mutations, 4 double mutations, and 2 triple mutations of IAPP that appear to be less amyloidogenic than wild-type human IAPP. A comparison of these sequences suggests residues 13 and 15-17 comprise an additional aggregation-prone region outside of the main amyloidogenic region of IAPP.