Both Caspase and Calpain are Involved in Endoplasmic Reticulum-Targeted BNIP3-Induced Cell Death.

Bcl-2/E1B-19K-interacting protein 3 (BNIP3) is a member of the apoptotic B-cell lymphoma-2 family that regulates cell death. Although BNIP3 targeted normally to the mitochondrial outer membrane by its transmembrane domain was originally considered to be essential for its pro-apoptotic activity, accumulating evidence has shown that BNIP3 is localized to endoplasmic reticulum at physiological conditions and that forced expression of BNIP3 can initiate cell death via multiple pathways depending on the subcellular compartment it targets. Targeting BNIP3 to endoplasmic reticulum has been shown to participate in cell death during endoplasmic reticulum stress. However, the molecular events responsible for BNIP3-induced cell death in the endoplasmic reticulum remain poorly understood. In the present study, the transmembrane domain of BNIP3 was replaced with a segment of cytochrome b5 that targets BNIP3 into endoplasmic reticulum, which induced cell death as effectively as its wild-type molecule in the SW480 cell line (colon carcinoma). Furthermore, a pan-caspase inhibitor, z-VAD-fmk, and PD150606, a specific calpain inhibitor, both significantly suppressed the endoplasmic reticulum-targeted BNIP3-induced cell death. These results suggest that endoplasmic reticulum-targeted BNIP3 induced a mixed mode of cell death requiring both caspases and calpains.

A piecewise geometric analysis method for real-time ambulatory ECG detection.

BACKGROUND: As one of the pervasive healthcare services, Ubiquitous cardiac care (UCC) systems should have at least two significant characteristics: real-time detection capability for cardiac arrhythmia events and a small resource requirement for its computation and storage. PURPOSE: Due to the strict-constrained system support and ambulatory signal quality in the out-of-hospital pervasive healthcare applications, a dedicated real-time AED (Ambulatory Electrocardiograph Detection) algorithm has been implemented. METHODOLOGY: By adopting the piecewise geometric analysis method, this algorithm can provide a real-time continuous detection capability for QRS complexes, which consists of three main functional modules: the Data preparation; the R-wave vertex discovery; and the QRS complex recognition. Currently, this algorithm has been applied on an on-line UCC application system at the hospital for more than 30 patients. RESULT: The performance evaluation has been made not only on the standard MIT-BIH cardiac arrhythmia database but also on the clinical testing. The experiential results explore this algorithm has in average sensitivity of 99.37% and specificity of 99.72%. CONCLUSION: This AED algorithm has minimal beat detection latency and a less computation consumption, which make it meet the requirements of ubiquitous cardiac care applications.