1,323 research outputs found

    YAF2 promotes TP53-mediated genotoxic stress response via stabilization of PDCD5

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    AbstractProgrammed cell death 5 (PDCD5) plays a crucial role in TP53-mediated apoptosis, but the regulatory mechanism of PDCD5 itself during apoptosis remains obscure. We identified YY1-associated factor 2 (YAF2) as a novel PDCD5-interacting protein in a yeast two-hybrid screen for PDCD5-interacting proteins. We found that YY1-associated factor 2 (YAF2) binds to and increases PDCD5 stability by inhibiting the ubiquitin-dependent proteosomal degradation pathway. However, knocking-down of YAF2 diminishes the levels of PDCD5 protein but not the levels of PDCD5 mRNA. Upon genotoxic stress response, YAF2 promotes TP53 activation via association with PDCD5. Strikingly, YAF2 failed to promote TP53 activation in the deletion of PDCD5, whereas restoration of wild-type PDCD5WT efficiently reversed the ineffectiveness of YAF2 on TP53 activation. Conversely, PDCD5 efficiently overcame the knockdown effect of YAF2 on ET-induced TP53 activation. Finally, impaired apoptosis upon PDCD5 ablation was substantially rescued by restoration of PDCD5WT but not YAF2-interacting defective PDCD5E4D nor TP53-interacting defective PDCD5E16D mutant. Our findings uncovered an apoptotic signaling cascade linking YAF2, PDCD5, and TP53 during genotoxic stress responses

    Concomitant renal insufficiency and diabetes mellitus as prognostic factors for acute myocardial infarction

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    <p>Abstract</p> <p>Background</p> <p>Diabetes mellitus and renal dysfunction are prognostic factors after acute myocardial infarction (AMI). However, few studies have assessed the effects of renal insufficiency in association with diabetes in the context of AMI. Here, we investigated the clinical outcomes according to the concomitance of renal dysfunction and diabetes mellitus in patients with AMI.</p> <p>Methods</p> <p>From November 2005 to August 2008, 9905 patients (63 ± 13 years; 70% men) with AMI were enrolled in a nationwide prospective Korea Acute Myocardial Infarction Registry (KAMIR) and were categorized into 4 groups: Group I (n = 5700) had neither diabetes nor renal insufficiency (glomerular filtration rate [GFR] ≥ 60 ml/min/1.73 m<sup>2</sup>), Group II (n = 1730) had diabetes but no renal insufficiency, Group III (n = 1431) had no diabetes but renal insufficiency, and Group IV (n = 1044) had both diabetes and renal insufficiency. The primary endpoints were major adverse cardiac events (MACE), including a composite of all cause-of-death, myocardial infarction, target lesion revascularization, and coronary artery bypass graft after 1-year clinical follow-up.</p> <p>Results</p> <p>Primary endpoints occurred in 1804 (18.2%) patients. There were significant differences in composite MACE among the 4 groups (Group I, 12.5%; Group II, 15.7%; Group III, 30.5%; Group IV, 36.5%; <it>p </it>< 0.001). In a Cox proportional hazards model, after adjusting for multiple covariates, the 1-year mortality increased stepwise from Group III to IV as compared with Group I (hazard ratio [HR], 1.96; 95% confidence interval [CI], 1.34-2.86; <it>p </it>= 0.001; and HR, 2.42; 95% CI, 1.62-3.62; <it>p </it>< 0.001, respectively). However, Kaplan-Meier analysis showed no significant difference in probability of death at 1 year between Group III and IV (p = 0.288).</p> <p>Conclusions</p> <p>Renal insufficiency, especially in association with diabetes, is associated with the occurrence of composite MACE and indicates poor prognosis in patients with AMI. Categorization of patients with diabetes and/or renal insufficiency provides valuable information for early-risk stratification of AMI patients.</p

    Does CSR image matter to hypermarket’s consumers in Malaysia? perspective from persuasion knowledge model

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    It is commonly accepted that positive corporate social responsibility (CSR) image brings desirable outcomes, for instance, brand loyalty, improved brand image, enhanced store image, as well as increased visit intention; suggesting there are various direct outcomes of CSR image. Underpinned by the Persuasion Knowledge Model (PKM), this paper proposes that these outcomes are presented in a sequential manner, where there is a core mechanism that relates CSR image to store image and brand awareness, and in turn associate with consumers’ visit intention. A quantitative research methodology has been used where a structured questionnaire was distributed to consumers in selected states in Malaysia using the mall intercept method. Structural equation modelling was applied to examine the proposed model. The discoveries of the current study offer the observed evidence for the correlation between perceived CSR image and hypermarket visit intention, mediated by overall store image and brand awareness. The study emphasises a prominent role of CSR schemes, bringing together the overall hypermarket store image and the hypermarket brand awareness, which will enable hypermarket management to further boost visit intention from consumers

    Receiver Operating Characteristic (ROC) Curve: Practical Review for Radiologists

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    The receiver operating characteristic (ROC) curve, which is defined as a plot of test sensitivity as the y coordinate versus its 1-specificity or false positive rate (FPR) as the x coordinate, is an effective method of evaluating the performance of diagnostic tests. The purpose of this article is to provide a nonmathematical introduction to ROC analysis. Important concepts involved in the correct use and interpretation of this analysis, such as smooth and empirical ROC curves, parametric and nonparametric methods, the area under the ROC curve and its 95% confidence interval, the sensitivity at a particular FPR, and the use of a partial area under the ROC curve are discussed. Various considerations concerning the collection of data in radiological ROC studies are briefly discussed. An introduction to the software frequently used for performing ROC analyses is also presented

    The reemergence of long-term potentiation in aged Alzheimer's disease mouse model

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    Mouse models of Alzheimer’s disease (AD) have been developed to study the pathophysiology of amyloid β protein (Aβ) toxicity, which is thought to cause severe clinical symptoms such as memory impairment in AD patients. However, inconsistencies exist between studies using these animal models, specifically in terms of the effects on synaptic plasticity, a major cellular model of learning and memory. Whereas some studies find impairments in plasticity in these models, others do not. We show that long-term potentiation (LTP), in the CA1 region of hippocampal slices from this mouse, is impared at Tg2576 adult 6–7 months old. However, LTP is inducible again in slices taken from Tg2576 aged 14–19 months old. In the aged Tg2576, we found that the percentage of parvalbumin (PV)-expressing interneurons in hippocampal CA1-3 region is significantly decreased, and LTP inhibition or reversal mediated by NRG1/ErbB signaling, which requires ErbB4 receptors in PV interneurons, is impaired. Inhibition of ErbB receptor kinase in adult Tg2576 restores LTP but impairs depotentiation as shown in aged Tg2576. Our study suggests that hippocampal LTP reemerges in aged Tg2576. However, this reemerged LTP is an insuppressible form due to impaired NRG1/ErbB signaling, possibly through the loss of PV interneurons

    Does gender influence the impact of impaired renal function on prognosis after ST-segment elevated myocardial infarction?

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    Background: A limited number of studies have investigated the impact of gender on renal function and clinical outcomes after ST-segment elevated myocardial infarction (STEMI), and these studies have provided discrepant results.Methods and Results: This study was based on a retrospective cohort, the Korean Acute Myocardial Infarction Registry (KAMIR). Patients (n = 7,679) with a discharge diagnosis of STEMI were analyzed to investigate association of gender with renal function and clinical outcomes. Compared to men, women were older and exhibited more comorbidity, including impaired renal function. Women showed higher mortality compared to men (1-month mortality,5.6% in men vs. 12.6% in women, p &lt; 0.001; 1-year mortality, 6.8% in men vs. 14.4% in women, p &lt; 0.001). The risk of death proportionally increased as estimated glomerular filtration rate (eGFR) decreased in both genders. After adjusting for potential confounders, hazard ratios for women did not significantly differ from those for men at each eGFR level.The interaction test showed no significant interaction between gender and eGFR in 1-month mortality and 1-year mortality.Conclusions: Impaired renal function was an independent prognostic factor after STEMI in both genders, and the impact of impaired renal function on prognosis after STEMI did not significantly differ between genders

    Acute Diffuse Phlegmonous Esophagogastritis: A Case Report

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    Acute phlegmonous infection of the gastrointestinal tract is characterized by purulent inflammation of the submucosa and muscular layer with sparing of the mucosa. The authors report a rare case of acute diffuse phlegmonous esophagogastritis, which was well diagnosed based on the typical chest computed tomographic (CT) findings and was successfully treated. A 48-yr-old man presented with left chest pain and dyspnea for three days. Chest radiograph on admission showed mediastinal widening and bilateral pleural effusion. The patient became febrile and the amount of left pleural effusion is increased on follow-up chest radiograph. Left closed thoracostomy was performed with pus drainage. A CT diagnosis of acute phlegmonous esophagogastritis was suggested and a surgery was decided due to worsening of clinical condition of the patient and radiologic findings. Esophageal myotomies were performed and the submucosal layer was filled with thick, cheesy materials. The patient was successfully discharged with no postoperative complication
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