Summary The melanized yeast Exophiala dermatitidis is resistant to many environmental stresses and is used as a model for understanding the diverse roles of melanin in fungi. Here, we describe the extent of resistance of E. dermatitidis to acute γ‐radiation exposure and the major mechanisms it uses to recover from this stress. We find that melanin does not protect E. dermatitidis from γ‐radiation. Instead, environmental factors such as nutrient availability, culture age and culture density are much greater determinants of cell survival after exposure. We also observe a dramatic transcriptomic response to γ‐radiation that mobilizes pathways involved in morphological development, protein degradation and DNA repair, and is unaffected by the presence of melanin. Together, these results suggest that the ability of E. dermatitidis to survive γ‐radiation exposure is determined by the prior and the current metabolic state of the cells as well as DNA repair mechanisms, and that small changes in these conditions can lead to large effects in radiation resistance, which should be taken into account when understanding how diverse fungi recover from this unique stress.

Using all-atom explicit water model and replica exchange molecular dynamics, we study the interactions between Aβ monomer and nonsteroidal anti-inflammatory drug ibuprofen, which is known to reduce the risk of Alzheimer's disease. Ibuprofen binding to Aβ is largely governed by hydrophobic effect, and its binding site in Aβ peptide is entirely composed of hydrophobic amino acids. Electrostatic interactions between negatively charged ibuprofen ligands and positively charged side chains make a relatively small contribution to binding. This outcome is explained by the competition of ligand-peptide electrostatic interactions with intrapeptide salt bridges. Consistent with the experiments, the S-isomer of ibuprofen binds with stronger affinity to Aβ than the R-isomer. Conformational ensemble of Aβ monomer in ibuprofen solution reveals two structured regions, 19-25 (R1) and 29-35 (R2), composed of turn/helix and helix structure, respectively. The clustering technique and free energy analysis suggest that Aβ conformational ensemble is mainly determined by the formation of Asp23-Lys28 salt bridge and the hydrophobic interactions between R1 and R2. Control simulations of Aβ peptide in ligand-free water show that ibuprofen binding changes Aβ structure by promoting the formation of helix and Asp23-Lys28 salt bridge. Implications of our findings for Aβ amyloidogenesis are discussed.

Although the oligomers formed by Aβ peptides appear to be the primary cytotoxic species in Alzheimer's disease, detailed information about their structures appears to be lacking. In this article, we use exhaustive replica exchange molecular dynamics and an implicit solvent united-atom model to study the structural properties of Aβ monomers, dimers, and tetramers. Our analysis suggests that the conformational ensembles of Aβ dimers and tetramers are very similar, but sharply distinct from those sampled by the monomers. The key conformational difference between monomers and oligomers is the formation of β-structure in the oligomers occurring together with the loss of intrapeptide interactions and helix structure. Our simulations indicate that, independent of oligomer order, the Aβ aggregation interface is largely confined to the sequence region 10-23, which forms the bulk of interpeptide interactions. We show that the fractions of β structure computed in our simulations and measured experimentally are in good agreement.

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An investigation of the microstructural evolution and dissolution phenomena in a Ti(C 0.7 N 0.3 )-xWC-yNbC-20Ni system is reported. In Ti(C 0.7 N 0.3 )-yNbC-20Ni systems, a phase separation occurs between the Ti(CN) core and the (Ti,Nb)(CN) rim phases when the system contains >15 wt% NbC. This phase separation results from the increased misfit between the cores and the solid-solution rim phases with the addition of NbC. Based on data obtained from a previous study and compositional analyses of the rim structure of the Ti(C 0.7 N 0.3 )-yNbC20Ni system, the average dissolution rates of WC and NbC appear to be approximately the same with respect to that of Ti(CN), under given sintering conditions (1510°C for 1 h). In addition, compositional changes in the rim structure of the Ti(C 0.7 N 0.3 )-xWC-yNbC-20Ni system are compared with those for a Ti(C 0.7 N 0.3 )-xWC-20Ni system to explain the effect of NbC on WC dissolution in the Ti(C 0.7 N 0.3 )-WC-NbC-Ni system. The presence of NbC in the Ti(C 0.7 N 0.3 )-xWC-20Ni system is found to suppress the dissolution of WC.