The naked mole-rat is a subterranean rodent, approximately the size of a mouse, renowned for its exceptional longevity (>30 years) and remarkable resistance to cancer. To explore putative mechanisms underlying the cancer resistance of the naked mole-rat, we investigated the regulation and function of the most commonly mutated tumor suppressor, TP53, in the naked mole-rat.  https://www.selleckchem.com/products/resatorvid.html  We found that the p53 protein in naked mole-rat embryonic fibroblasts (NEFs) exhibits a half-life more than ten times in excess of the protein's characterized half-life in mouse and human embryonic fibroblasts. We determined that the long half-life of the naked mole-rat p53 protein reflects protein-extrinsic regulation. Relative to mouse and human p53, a larger proportion of naked mole-rat p53 protein is constitutively localized in the nucleus prior to DNA damage. Nevertheless, DNA damage is sufficient to induce activation of canonical p53 target genes in NEFs. Despite the uniquely long half-life and unprecedented basal nuclear localization of p53 in NEFs, naked mole-rat p53 retains its canonical tumor suppressive activity. Together, these findings suggest that the unique stabilization and regulation of the p53 protein may contribute to the naked mole-rat's remarkable resistance to cancer.The diagnostic procedure for upper aerodigestive tract (UADT) tumours is by white light endoscopy (WLE) combined with biopsy. However, WLE has difficulty identifying minute epithelial changes which hinders early diagnosis. Storz Professional Image Enhancement System (SPIES) is designed to enhance the visualization of microvasculature on the mucosal surface and detect any epithelial changes. In this study, we aimed to evaluate the use of Ni endoscopic classification with SPIES endoscopy in the detection of UADT tumours. Fifty-nine patients with suspected UADT tumours underwent WLE followed by SPIES endoscopy. All the tumours were biopsied and sent for histopathological examination (HPE). The kappa index (κ) was used to evaluate the agreement between the methods. The level of agreement between SPIES using Ni classification and HPE showed almost perfect agreement as compared to moderate agreement between WLE and HPE. The sensitivity and specificity for WLE and HPE were 77.5% and 84.2% respectively with positive predictive value (PPV) of 91.2% and negative predictive value (NPV) of 64%. The sensitivity and specificity for SPIES endoscopy using Ni classification and HPE were 97.5% and 94.7% respectively with PPV of 97.5% and NPV of 94.7%. SPIES endoscopy using Ni classification is a valid tool for earlier tumour detection.In contrast to the vast majority of reptiles, the skulls of adult crown birds are characterized by a high degree of integration due to bone fusion, e.g., an ontogenetic event generating a net reduction in the number of bones. To understand this process in an evolutionary context, we investigate postnatal ontogenetic changes in the skulls of crown bird and non-avian theropods using anatomical network analysis (AnNA). Due to the greater number of bones and bone contacts, early juvenile crown birds have less integrated skulls, resembling their non-avian theropod ancestors, including Archaeopteryx lithographica and Ichthyornis dispars. Phylogenetic comparisons indicate that skull bone fusion and the resulting modular integration represent a peramorphosis (developmental exaggeration of the ancestral adult trait) that evolved late during avialan evolution, at the origin of crown-birds. Succeeding the general paedomorphic shape trend, the occurrence of an additional peramorphosis reflects the mosaic complexity of the avian skull evolution.We investigated if clinical outcomes after kidney transplantation (KT) from deceased donors (DDs) with high Kidney Donor Profile Index (KDPI) can be different according to the age of KT recipients (KTRs). Six-hundred fifty-seven KTRs from 526 DDs were included from four transplant centers. We divided KTRs into elderly-KTR and young-KTR groups based on age 60 and each group was subdivided into high- or low-KDPI subgroup based on KDPI score of 65%. We compared short-term and long-term clinical outcomes among those four subgroups (low KDPI-young KTR, low KDPI-elderly-KTR, high KDPI-young-KTR, high KDPI-elderly-KTR). In short-term outcomes including acute rejection, BK virus and CMV infection, there was no significant difference among the four subgroups. In the long-term outcomes, the development of cardiovascular disease was higher in the high KDPI-elderly-KTR group than the other groups. In comparison of allograft survival rate, the high KDPI-young KTR subgroup showed highest risk for allograft failure and there was significant interaction between high-KDPI donors and young-KTR on allograft survival rate (P = 0.002). However, there was no significant difference in comparison of the patient survival rate. In conclusion, clinical impact of high-KDPI in DDs on post-transplant allograft survival may be less significant in elderly-KTR than in young-KTR.To better define the role of FOXO1 and FOXO3 transcriptional factors in breast carcinogenesis, we performed a comparative study of their expression at both the RNA and protein levels in a series of human breast tumors. We used qRT-PCR assay to quantify mRNA expression and Reverse Phase Protein Arrays (RPPA) to quantify protein expression in 218 breast tumors from patients with known clinical/pathological status and outcome. Weak correlations were observed between mRNA and protein expressions for both FOXO1 and FOXO3 genes. High expression of FOXO3 protein, but not FOXO1 protein, was a good prognostic marker, negatively correlated with KI67 and markers of activity of the PI3K/AKT/mTOR oncogenic pathway, and positively correlated with p53, a marker of apoptosis. Moreover, FOXO3 protein expression, but not FOXO1 protein expression, was also negatively correlated with various proteins involved in different DNA repair mechanisms. FOXO3 protein, but not FOXO1 protein, appears to be a tumor suppressor that inhibits breast cancer by altering DNA damage response (DDR), thereby inducing p53-dependent apoptosis. This antitumor effect appears to be suppressed by excessive activity of the PI3K/AKT/mTOR pathway. High FOXO3 protein expression could be a biomarker of deficient DDR in breast tumors.