The p53 tumor suppressor protein is susceptible to oxidation, which prevents it from binding to its DNA response element. The goal of the current research was to determine the nature of the cysteine residue thiol oxidation that prevents p53 from binding its DNA target and its effect on p53 structure. Recombinant p53, purified in the presence of the reducing agent dithiothreitol (DTT), contains five free thiol groups on the surface of the protein. In the absence of DTT, p53 contains only four thiol groups, indicating that an average of one surface thiol group is readily susceptible to oxidation. Sulfite-mediated disulfide bond cleavage followed by reaction with 2-nitro-5-thiosulfobenzoate showed that oxidized p53 contains a single disulfide bond per monomer. By atomic force microscopy, we determined that reduced p53 binds to a double-stranded DNA containing the p53 promoter element of the MDM2 gene. The DNA-bound reduced p53 has an average cross-sectional diameter of 8.61 nm and a height of 4.12 nm. The amount of oxidized p53 that bound to the promoter element was ninefold lower, and it has an 18% larger average cross-sectional diameter. Electromobility shift assays showed that binding of oxidized p53 to DNA was enhanced upon addition of DTT, indicating that oxidation is reversible. The possibility that oxidized p53 contained significant amounts of sulfenic (-SOH), sulfinic (-SO2H), or sulfonic acid (-SO3H) was ruled out. Gel filtration chromatography indicated that oxidation increases the percentage of p53 monomers and high-molecular-weight oligomers (>1,000 kDa) relative to tetrameric p53. Protein modeling studies suggest that a mixed disulfide glutathione adduct on Cys182 could account for the observed stoichiometry of oxidized thiols and structural changes. The glutathione adduct may prevent proper helix-helix interaction within the DNA binding domain and contribute to tetramer dissociation.

Using a large panel of US bank holding companies from 2001 to 2015, we investigate the association between functional diversification and bank earnings management. We document a positive relationship between bank earnings management and bank diversification. Our findings are consistent with the hypothesis that diversification increases the asymmetric information of banks, leading to greater discretionary power by bank managers. This effect is most prevalent in smaller banks and non-dividend paying banks. The impact of diversification on earnings management is less pronounced during the crisis. Our study is of interest to regulators and other stakeholders who examine factors which affect behavior of bank managers. About the Authors: Viet-DungTran is affiliated with the Center for Studies and Applied Research in Management (CERAG) and Université Grenoble Alpes. He pursues research on the capital structure of Vietnamese banks. M.

We employed an island biogeographic approach to determine whether small fragments of the shrub habitats coastal sage scrub and chaparral, isolated by urbanization, are capable of supporting viable populations of native rodent species. The distribution of native rodents in 25 urban habitat fragments was assessed by live-trapping. Over half of the fragments surveyed (13 of 25) did not support populations of native rodents. Fragments supported fewer species than equivalently sized plots in large expanses of unfragmented habitat, and older fragments (fragments that had been isolated for a longer period of time) supported fewer species. Both results implied that local extinctions occurred in the fragments following insularization. Stepwise multiple polychotomous logistic regression was used to determine which biogeographic variables were the best predictors of species number across fragments. The area of shrub habitat in each fragment was the most significant predictor of species diversity; age of a fragment was also significant and was negatively correlated with species number, but the isolation distance of a fragment had no relationship to species diversity. We found a negative relationship between extinction vulnerability of native rodent species and relative abundance: species that were more abundant in unfragmented habitat persisted in more habitat fragments. Random environmental and demographic fluctuations (island effects) and edge effects associated with fragmentation are proposed as causes of these local extinctions.

Does dividend policy increase or decrease bank opaqueness? Under the Dividend–Transparency Channel, paying dividends involves banks having greater discipline from the markets due to external financing and reduces private benefits of control, leading to lower earnings management concerns. Under the Dividend–Opacity Channel, due to a hesitancy to change dividend policy, banks have high vocations to engage earnings management to circumvent payout policy restrictions in debt covenants or to keep their dividend target unchanged. Employing a large sample of 2,483 U.S. bank holding companies from 2001:Q1–2013:Q4, the study documents the double‐edged sword of dividends on the discretionary behaviours of banks. Paying dividends makes banks less opaque to compare with nonpayers, which is consistent with the Dividend–Transparency Channel, however among dividend paying banks, excessive dividends involve banks to manage more their numbers, which is consistent with the Dividend–Opacity Channel. The findings are robust under different specifications. The results are of important interest to bank regulators.