Transcription Factor AP4 Mediates Cell Fate Decisions: To Divide, Age, or Die

Activating Enhancer-Binding Protein 4 (AP4)/transcription factor AP4 (TFAP4) is a basic-helix-loop-helix-leucine-zipper transcription factor that was first identified as a protein bound to SV40 promoters more than 30 years ago. Almost 15 years later, AP4 was characterized as a target of the c-Myc transcription factor, which is the product of a prototypic oncogene that is activated in the majority of tumors. Interestingly, AP4 seems to represent a central hub downstream of c-Myc and N-Myc that mediates some of their functions, such as proliferation and epithelial-mesenchymal transition (EMT). Elevated AP4 expression is associated with progression of cancer and poor patient prognosis in multiple tumor types. Deletion of AP4 in mice points to roles of AP4 in the control of stemness, tumor initiation and adaptive immunity. Interestingly, ex vivo AP4 inactivation results in increased DNA damage, senescence, and apoptosis, which may be caused by defective cell cycle progression. Here, we will summarize the roles of AP4 as a transcriptional repressor and activator of target genes and the contribution of protein and non-coding RNAs encoded by these genes, in regulating the above mentioned processes. In addition, proteins interacting with or regulating AP4 and the cellular signaling pathways altered after AP4 dysregulation in tumor cells will be discussed

Increased Risk of Vascular Events in Emergency Room Patients Discharged Home with Diagnosis of Dizziness or Vertigo: A 3-Year Follow-Up Study

BACKGROUND: Dizziness and vertigo symptoms are commonly seen in emergency room (ER). However, these patients are often discharged without a definite diagnosis. Conflicting data regarding the vascular event risk among the dizziness or vertigo patients have been reported. This study aims to determine the risk of developing stroke or cardiovascular events in ER patients discharged home with a diagnosis of dizziness or vertigo. METHODOLOGY: A total of 25,757 subjects with at least one ER visit in 2004 were identified. Of those, 1,118 patients were discharged home with a diagnosis of vertigo or dizziness. A Cox proportional hazard model was performed to compare the three-year vascular event-free survival rates between the dizziness/vertigo patients and those without dizziness/vertigo after adjusting for confounding and risk factors. RESULTS: We identified 52 (4.7%) vascular events in patients with dizziness/vertigo and 454 (1.8%) vascular events in patients without dizziness/vertigo. ER patients discharged home with a diagnosis of vertigo or dizziness had 2-fold (95% confidence interval [CI], 1.35-2.96; p<0.001) higher risk of stroke or cardiovascular events after adjusting for patient characteristics, co-morbidities, urbanization level of residence, individual socio-economic status, and initially taking medications after the onset of dizziness or vertigo during the first year. CONCLUSIONS: ER patients discharged home with a diagnosis of dizziness or vertigo were at a increased risk of developing subsequent vascular events than those without dizziness/vertigo after the onset of dizziness or vertigo. Further studies are warranted for developing better diagnostic and follow-up strategies in increased risk patients

Differential Actions of Chlorhexidine on the Cell Wall of Bacillus subtilis and Escherichia coli

Chlorhexidine is a chlorinated phenolic disinfectant used commonly in mouthwash for its action against bacteria. However, a comparative study of the action of chlorhexidine on the cell morphology of Gram-positive and Gram-negative bacteria is lacking. In this study, the actions of chlorhexidine on the cell morphology were identified with the aids of electron microscopy. After exposure to chlorhexidine, numerous spots of indentation on the cell wall were found in both Bacillus subtilis and Escherichia coli. The number of indentation spots increased with time of incubation and increasing chlorhexidine concentration. Interestingly, the dented spots found in B. subtilis appeared mainly at the hemispherical caps of the cells, while in E. coli the dented spots were found all over the cells. After being exposed to chlorhexidine for a prolonged period, leakage of cellular contents and subsequent ghost cells were observed, especially from B subtilis. By using 2-D gel/MS-MS analysis, five proteins related to purine nucleoside interconversion and metabolism were preferentially induced in the cell wall of E. coli, while three proteins related to stress response and four others in amino acid biosynthesis were up-regulated in the cell wall materials of B. subtilis. The localized morphological damages together with the biochemical and protein analysis of the chlorhexidine-treated cells suggest that chlorhexidine may act on the differentially distributed lipids in the cell membranes/wall of B. subtilis and E. coli

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Aggregation and DNA intercalation properties of Di(isocyano) rhodium(I) Diimine complexes

A series of di(isocyano) rhodium(I) diimine complexes has been synthesized and characterized. Owing to the aggregation affinity of these complexes, they were found to exhibit thermochromism. To provide further insights into the aggregation affinity of these complexes, the enthalpy (δH) and entropy (δS) changes of dimerizations of some of the complexes have been determined. In addition, the DNA intercalation properties of these complexes have also been investigated by the DNA unwinding assay