A New p53 Target Gene, RKIP, Is Essential for DNA Damage-Induced Cellular Senescence and Suppression of ERK Activation

Abstractp53, a strong tumor suppressor protein, is known to be involved in cellular senescence, particularly premature cellular senescence. Oncogenic stresses, such as Ras activation, can initiate p53-mediated senescence, whereas activation of the Ras-mitogen-activated protein kinase (MAPK) pathway can promote cell proliferation. These conflicting facts imply that there is a regulatory mechanism for balancing p53 and Ras-MAPK signaling. To address this, we evaluated the effects of p53 on the extracellular signal-regulated kinase (ERK) activation and found that p53 could suppress ERK activation through de novo synthesis. Through several molecular biologic analyses, we found that RKIP, an inhibitor of Raf kinase, is responsible for p53-mediated ERK suppression and senescence. Overexpression of RKIP can induce cellular senescence in several types of cell lines, including p53-deficient cells, whereas the elimination of RKIP by siRNA or forced expression of ERK blocks p53-mediated cellular senescence. These results suggested that RKIP is an essential protein for cellular senescence. Moreover, modification of the p53 serine 46 residue was critical for RKIP induction and ERK suppression as well as cellular senescence. These results indicated that RKIP is a novel p53 target gene that is responsible for p53-mediated cellular senescence and tumor suppressor protein expression

Identification of protein functions using a machine-learning approach based on sequence-derived properties

<p>Abstract</p> <p>Background</p> <p>Predicting the function of an unknown protein is an essential goal in bioinformatics. Sequence similarity-based approaches are widely used for function prediction; however, they are often inadequate in the absence of similar sequences or when the sequence similarity among known protein sequences is statistically weak. This study aimed to develop an accurate prediction method for identifying protein function, irrespective of sequence and structural similarities.</p> <p>Results</p> <p>A highly accurate prediction method capable of identifying protein function, based solely on protein sequence properties, is described. This method analyses and identifies specific features of the protein sequence that are highly correlated with certain protein functions and determines the combination of protein sequence features that best characterises protein function. Thirty-three features that represent subtle differences in local regions and full regions of the protein sequences were introduced. On the basis of 484 features extracted solely from the protein sequence, models were built to predict the functions of 11 different proteins from a broad range of cellular components, molecular functions, and biological processes. The accuracy of protein function prediction using random forests with feature selection ranged from 94.23% to 100%. The local sequence information was found to have a broad range of applicability in predicting protein function.</p> <p>Conclusion</p> <p>We present an accurate prediction method using a machine-learning approach based solely on protein sequence properties. The primary contribution of this paper is to propose new <it>PNPRD </it>features representing global and/or local differences in sequences, based on positively and/or negatively charged residues, to assist in predicting protein function. In addition, we identified a compact and useful feature subset for predicting the function of various proteins. Our results indicate that sequence-based classifiers can provide good results among a broad range of proteins, that the proposed features are useful in predicting several functions, and that the combination of our and traditional features may support the creation of a discriminative feature set for specific protein functions.</p

Surface Characteristics of Orthodontic Materials and Their Effects on Adhesion of Mutans streptococci

Objective: To test the hypothesis that there are no significant differences in the adhesion of mutans streptococci (MS) to various orthodontic materials based on their surface characteristics. Materials and Methods: Surface roughness (SR) and surface free energy (SFE) characteristics were investigated for nine different orthodontic materials (four orthodontic adhesives, three bracket raw materials, hydroxyapatite blocks, and bovine incisors) using confocal laser scanning microscopy and sessile drop method. Each material, except the bovine incisors, was incubated with whole saliva or phosphate-buffered saline for 2 hours. Adhesion assays were performed by incubating tritium-labeled MS with each material for 3 or 6 hours. Results: Orthodontic adhesives had higher SFE characteristics and lower SR than bracket materials. Orthodontic adhesives showed a higher MS retaining capacity than bracket materials, and MS adhesion to resin-modified glass ionomer and hydroxyapatite was highest. Extended incubation time increased MS adhesion, while saliva coating did not significantly influence MS adhesion. SFE, specifically its dispersive and polar components, was positively correlated with MS adhesion, irrespective of saliva coating. Conclusions: The hypothesis is rejected. This study suggests that SFE characteristics play an important role in the initial MS adhesion to orthodontic materials.This study was supported by a grant from the Korea Health 21 Project, Ministry of Health and Welfare, Republic of Korea (03-PJ1-PG1-CH09-0001)

Orthogonal Stability of an Additive-quartic Functional Equation in Non-Archimedean Spaces

Using fixed point method, we prove the Hyers-Ulam stability of the orthogonally additive-quartic functional equation f(2x+y)+ f(2x-y)=4 f(x+y)+ 4 f(x-y) + 10 f(x) + 14f(-x) - 3 f(y)-3f(-y) for all $x, y$ with $xperp y$, in non-Archimedean Banach spaces. Here $perp$ is the orthogonality in the sense of Rätz

Surgical repair of descending thoracic and thoracoabdominal aortic aneurysm involving the distal arch: Open proximal anastomosis under deep hypothermia versus arch clamping technique

BackgroundSurgical repair of a descending thoracic and thoracoabdominal aortic aneurysm (DTA/TAAA) involving the distal arch is challenging and requires either deep hypothermic circulatory arrest (DHCA) or crossclamping of the distal arch. The aim of this study was to compare these 2 techniques in the treatment of DTA/TAAA involving the distal arch.MethodsFrom 1994 to 2012, 298 patients underwent open repair of DTA/TAAA through a left thoracotomy. One hundred seventy-four patients with distal arch involvement who were suitable for either DHCA (n = 81) or arch clamping (AC; n = 93), were analyzed. In-hospital outcomes were compared using propensity scores and inverse-probability-of-treatment weighting adjustment to reduce treatment selection bias.ResultsEarly mortality was 11.1% in the DHCA group and 8.6% in the AC group (P = .58). Major adverse outcomes included stroke in 16 patients (9.2%), low cardiac output syndrome in 15 (8.6%), paraplegia in 10 (5.7%), and multiorgan failure in 10 (5.7%). After adjustment, patients who underwent DHCA were at similar risk of death (odds ratio [OR], 1.14; P = .80) and permanent neurologic injury (OR, 0.95; P = .92) to those who underwent AC. Although prolonged ventilator support (>24 hours) was more frequent with DHCA than with AC (OR, 2.60; P = .003), DHCA showed a tendency to lower the risk of paraplegia (OR, 0.15; P = .057).ConclusionsCompared with AC, DHCA did not increase postoperative mortality and morbidity, except for prolonged ventilator support. However, DHCA may offer superior spinal cord protection to AC during repair of DTA/TAAA involving the distal arch

Titanium Plate Fixation for a Dehisced Sternum Following Coronary Artery Bypass Grafting: A Case Report

Sternal dehiscence is one of the most troublesome complications following cardiac surgery. Treatment failure and consequent lethal results are very common, even with all the efforts to resolve sternal dehiscence such as removal of infectious tissue, muscle flap interposition, and sternal rewiring. We report on a case of sternal osteomyelitis following coronary artery bypass grafting that was successfully treated with wide sternal resection, titanium plate fixation, and pectoralis muscle flap interposition

Male-Specific W4P/R Mutation in the Pre-S1 Region of Hepatitis B Virus, Increasing the Risk of Progression of Liver Diseases in Chronic Patients

The issue of hepatitis B virus (HBV) mutations possibly leading to a gender disparity in the progression of liver diseases has not been explored. We aimed to elucidate the relationships of the novel pre-S1 mutations, W4P/R, with the progression of liver diseases and male predominance in a South Korean chronic cohort by use of a molecular epidemiologic study. We developed a fluorescence resonance energy transfer (FRET)-based real-time PCR (RT-PCR) assay for the detection of the W4P/R mutations and applied it to 292 chronic HBV patients. The pre-S1 mutations from 247 (84.6%) of a total of 292 patients were detected by this assay. W4P/R mutants were found to be significantly related to severe liver diseases (hepatocellular carcinoma [HCC] and liver cirrhosis, 12.4% [19/153] of patients, versus chronic hepatitis and asymptomatic carriage, 1.1% [1/94] of patients) (P<0.001). All of the W4P/R mutants were found in males only. The novel HBV pre-S1 mutations, W4P/R, may be associated with disease severity in male patients chronically infected with HBV genotype C. The W4P/R mutations may provide in part an explanation for the relatively high ratio of male to female incidence in HCC generation in South Korean chronic HBV patients.OAIID:oai:osos.snu.ac.kr:snu2013-01/102/0000006653/6SEQ:6PERF_CD:SNU2013-01EVAL_ITEM_CD:102USER_ID:0000006653ADJUST_YN:YEMP_ID:A077651DEPT_CD:806CITE_RATE:4.068FILENAME:male-specific w4p_r mutation in the pre-s1.pdfDEPT_NM:의과학과EMAIL:[email protected]_YN:YCONFIRM:

The impact of sequential versus single anastomoses on flow characteristics and mid-term patency of saphenous vein grafts in coronary bypass grafting

ObjectiveTo assess the influence of bypass grafting technique on the flow characteristics and mid-term patency of saphenous vein coronary bypass grafts.MethodsIn the present study, 309 patients who underwent either sequential (group A, N = 84 grafts) or individual (group B, N = 244 grafts) saphenous vein coronary bypass grafting between February 2002 and September 2007 were investigated. Individual bypassing only was performed in 212 patients, and sequential bypassing only was performed in 78 patients. The remaining 19 patients received both. A total of 436 distal anastomoses were performed with 328 saphenous vein grafts. The intraoperative flow characteristics and the graft patency were assessed with the transit time flow meter and serial multi-detector computed tomography coronary angiograms, respectively.ResultsGroup A showed a higher mean flow compared with group B at 49.4 ± 27.4 mL/min versus 37.1 ± 20.1 mL/min, respectively (P = .001). The mean flow increased linearly as the number of anastomoses increased per graft (P < .001). Graft patency at 3 years was 93.3% ± 3.4% in group A and 86.5% ± 3.1% in group B (P = .048). After adjustment for baseline characteristics, group A showed a tendency for superior mid-term patency than group B (hazard ratio 0.362; 95% confidence interval, 0.129–1.017; P = .0538).ConclusionsSequential bypass grafts were associated with higher mean flows and superior mid-term patency compared with individual grafts. These findings suggest the more favorable results of sequential bypass grafting to be attributed to the enhanced flow hemodynamics