Peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PPARGC1A) regulates the expression of energy metabolism’s genes and mitochondrial biogenesis. The essential roles of PPARGC1A encouraged the researchers to assess the relation between metabolism-related diseases and its variants. To study Gly482Ser (+1564G/A) single-nucleotide polymorphism (SNP) after PPARGC1A modeling, we substitute Gly482 for Ser482. Stability prediction tools showed that this substitution decreases the stability of PPARGC1A or has a destabilizing effect on this protein. We then utilized molecular dynamics simulation of both the Gly482Ser variant and wild type of the PPARGC1A protein to analyze the structural changes and to reveal the conformational flexibility of the PPARGC1A protein. We observed loss flexibility in the RMSD plot of the Gly482Ser variant, which was further supported by a decrease in the SASA value in the Gly482Ser variant structure of PPARGC1A and an increase of H-bond with the increase of β-sheet and coil and decrease of turn in the DSSP plot of the Gly482Ser variant. Such alterations may significantly impact the structural conformation of the PPARGC1A protein, and it might also affect its function. It showed that the Gly482Ser variant affects the PPARGC1A structure and makes the backbone less flexible to move. In general, molecular dynamics simulation (MDS) showed more flexibility in the native PPARGC1A structure. Essential dynamics (ED) also revealed that the range of eigenvectors in the conformational space has lower extension of motion in the Gly482Ser variant compared with WT. The Gly482Ser variant also disrupts PPARGC1A interaction. Due to this single-nucleotide polymorphism in PPARGC1A, it became more rigid and might disarray the structural conformation and catalytic function of the protein and might also induce type 2 diabetes mellitus (T2DM), coronary artery disease (CAD), and nonalcoholic fatty liver disease (NAFLD). The results obtained from this study will assist wet lab research in expanding potent treatment on T2DM.
Introduction
Renal colic is one of the most common complaints in patients admitted to Emergency Department (ED). Computed Tomography (CT) is the reference standard for the diagnosis of any stones in the kidneys or ureters. However, CT has classical disadvantages, such as radiation exposure, cost and availability. Recently, STONE clinical prediction criteria were suggested to identify uncomplicated ureteral stone cases among patiens admitted to the ED with abdominal pain. Primary objective of this study was the external validation of the STONE criteria.
Methods
This was a diagnostic accuracy study conducted on a prospective, observational cohort. All consecutive patients who underwent a non-enhanced abdominopelvic CT scan in the ED with an initial diagnosis of ureteral stone disease were enrolled. Using a pre-prepared checklist, all data and the final diagnosis according to the CT scan were recorded. STONE score was calculated for all patients. The area under the curve (AUC) of the STONE Score and the CT, the reference standard, were compared using the ROC curve analysis.
Results
Totally, 237 patients (59.9% male) with an average age of 41.54 years (SD: 13.37) were evaluated, and 156 cases (65.8%) were proved to have renal stone. The mean (SD) STONE scores in the groups of patients with renal stone and in the group of patients without renal stone group were 9.1 (2.6) and 6.0 ( 2.8), respectively (p < 0.001). The area under the curve (AUC) for the STONE score was 0.789 (95% confidence interval (CI) 0.725 to 0.852). The optimum threshold value of the STONE score for the diagnosis of a renal stone was 8 or more, which had a sensitivity of 75.0% and a specificity of 70.4%.
Conclusion
Despite the acceptable diagnostic accuracy, further modifications and enhancements of the STONE score are needed to differentiate patients with low risk prior to imaging.
An author name was incorrectly spelled as "Sepideh Babanianmansour". The correct spelling is "Sepideh Babaniamansour".The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.
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