scholarly journals Canine SOD1 harboring E40K or T18S mutations promotes protein aggregation without reducing the global structural stability

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9512
Author(s):  
Shintaro Kimura ◽  
Yuji O. Kamatari ◽  
Yukina Kuwahara ◽  
Hideaki Hara ◽  
Osamu Yamato ◽  
...  

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease associated with aggregation of superoxide dismutase 1 (SOD1) protein. More than 160 mutations in human SOD1 have been identified in familial ALS and extensively characterized in previous studies. Here, we investigated the effects of T18S and E40K mutations on protein aggregation of canine SOD1. These two mutations are exclusively found in canine degenerative myelopathy (an ALS-like neurodegenerative disease in dogs), whose phenotype is unknown at the level of protein folding. Interestingly, the T18S and E40K mutations did not alter far-UV CD spectrum, enzymatic activity, or global structural stability of canine SOD1. However, thioflavin-T assay and transmission electron microscopy analysis revealed that these mutations promote formation of fibrous aggregates, in particular in the Cu2+/Zn2+-unbound state. These evidence suggested that the T18S and E40K mutations promote protein aggregation through a unique mechanism, possibly involving destabilization of the local structure, reduction of net negative charge, or production of disulfide-linked oligomers.

Materials ◽  
2021 ◽  
Vol 14 (6) ◽  
pp. 1332
Author(s):  
Florian Riedlsperger ◽  
Bernadette Gsellmann ◽  
Erwin Povoden-Karadeniz ◽  
Oriana Tassa ◽  
Susanna Matera ◽  
...  

A thermokinetic computational framework for precipitate transformation simulations in Ta-containing martensitic Z-steels was developed, including Calphad thermodynamics, diffusion mobility data from the literature, and a kinetic parameter setup that considered precipitation sites, interfacial energies and dislocation density evolution. The thermodynamics of Ta-containing subsystems were assessed by atomic solubility data and enthalpies from the literature as well as from the experimental dissolution temperature of Ta-based Z-phase CrTaN obtained from differential scanning calorimetry. Accompanied by a comprehensive transmission electron microscopy analysis of the microstructure, thermokinetic precipitation simulations with a wide-ranging and well-documented set of input parameters were carried out in MatCalc for one sample alloy. A special focus was placed on modelling the transformation of MX into the Z-phase, which was driven by Cr diffusion. The simulation results showed excellent agreement with experimental data in regard to size, number density and chemical composition of the precipitates, showing the usability of the developed thermokinetic simulation framework.


Author(s):  
Hongyan Xu ◽  
Jing Guo ◽  
Qing Meng ◽  
Zhanling Xie

<i>Morchella</i> is a genus of edible fungi with strong resistance to Cd and the ability to accumulate it in the mycelium. However, the mechanisms conferring Cd resistance in <i>Morchella</i> are unknown. In the present study, morphological and physiological responses to Cd were evaluated in the mycelia of <i>Morchella spongiola</i>. Variations in hyphal micro-morphology including twisting, folding and kinking in mycelia exposed to different Cd concentrations (0.15, 0.9, 1.5, 2.4, 5.0 mg/L) were observed using scanning electron microscopy. Deposition of Cd precipitates on cell surfaces (at Cd concentrations > 2.4 mg/L) was shown by SEM-EDS. Transmission electron microscopy analysis of cells exposed to different concentrations of Cd revealed the loss of intracellular structures and the localization of Cd depositions inside/outside the cell. FTIR analysis showed that functional groups such as C=O, -OH, -NH and -CH could be responsible for Cd binding on the cell surface of <i>M. spongiola</i>. In addition, intracellular accumulation was observed in cultures at low Cd concentrations (< 0.9 mg/L), while extracellular adsorption occurred at higher concentrations. These results provide valuable information on the Cd tolerance mechanism in <i>M. spongiola</i> and constitute a robust foundation for further studies on fungal bioremediation strategies.


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