A Rapidly Reversible Chemical Dimerizer System to Study Lipid Signaling in Living Cells

Chemical dimerizers are powerful tools for non‐invasive manipulation of enzyme activities in intact cells. Here we introduce the first rapidly reversible small‐molecule‐based dimerization system and demonstrate a sufficiently fast switch‐off to determine kinetics of lipid metabolizing enzymes in living cells. We applied this new method to induce and stop phosphatidylinositol 3‐kinase (PI3K) activity, allowing us to quantitatively measure the turnover of phosphatidylinositol 3,4,5‐trisphosphate (PIP₃) and its downstream effectors by confocal fluorescence microscopy as well as standard biochemical methods.     

Hysteresis of charge tunneling in assemblies of carboxylic acid-modified gold nanoparticles

We report on charge transport measurements through laterally contacted assemblies of Au nanoparticles capped with 11-mercaptoundecanoic acid ligands. Both alternating- and direct-current data indicate that although the nanoparticles behave as electrically isolated metallic islands, there is a significant influence from the nanoparticle environment, indicating the existence of a slow reorganization process linked to charge transport. On the basis of the observation of temperature-dependent hysteresis of charge tunneling, we propose that this process is due to proton transfer between the carboxylic acid tails of the ligands.     

Evaluation of the potential of Raman microspectroscopy for prediction of chemotherapeutic response to cisplatin in lung adenocarcinoma

The study of the interaction of anticancer drugs with mammalian cells in vitro is important to elucidate the mechanisms of action of the drug on its biological targets. In this context, Raman spectroscopy is a potential candidate for high throughput, non-invasive analysis. To explore this potential, the interaction of cis-diamminedichloroplatinum(II) (cisplatin) with a human lung adenocarcinoma cell line (A549) was investigated using Raman microspectroscopy. The results were correlated with parallel measurements from the MTT cytotoxicity assay, which yielded an IC(50) value of 1.2 ± 0.2 μM. To further confirm the spectral results, Raman spectra were also acquired from DNA extracted from A549 cells exposed to cisplatin and from unexposed controls. Partial least squares (PLS) multivariate regression and PLS Jackknifing were employed to highlight spectral regions which varied in a statistically significant manner with exposure to cisplatin and with the resultant changes in cellular physiology measured by the MTT assay. The results demonstrate the potential of the cellular Raman spectrum to non-invasively elucidate spectral changes that have their origin either in the biochemical interaction of external agents with the cell or its physiological response, allowing the prediction of the cellular response and the identification of the origin of the chemotherapeutic response at a molecular level in the cell.     

Cardiac magnetic resonance imaging: infarct size is an independent predictor of mortality in patients with coronary artery disease

Background

Cardiac magnetic resonance imaging (CMR) can accurately determine infarct size. Prior studies using indirect methods to assess infarct size have shown that patients with larger myocardial infarctions have a worse prognosis than those with smaller myocardial infarctions.

Objectives

This study assessed the prognostic significance of infarct size determined by CMR.

Methods

Cine and contrast CMR were performed in 100 patients with coronary artery disease (CAD) undergoing routine cardiac evaluation. Infarct size was determined by planimetry. We used Cox proportional hazards regression analyses (stepwise forward selection approach) to evaluate the risk of all-cause death associated with traditional cardiovascular risk factors, symptoms of heart failure, medication use, left ventricular ejection fraction, left ventricular mass, angiographic severity of CAD and extent of infarct size determined by CMR.

Results

Ninety-one patients had evidence of myocardial infarction by CMR. Mean follow-up was 4.8±1.6 years after CMR, during which time 30 patients died. The significant multivariable predictors of all-cause mortality were extent of myocardial infarction by CMR, extent of left ventricular systolic dysfunction, symptoms of heart failure, and diabetes mellitus (P<.05). The presence of infarct greater than or equal to 24% of left ventricular mass and left ventricular ejection fraction less than or equal to 30% were the most optimal cut-off points for the prediction of death with bivariate adjusted hazard ratios of 2.11 (95% confidence interval 1.02-4.38) and 4.06 (95% confidence interval 1.73-9.54), respectively.

Conclusions

The extent of myocardial infarction determined by CMR is an independent predictor of death in patients with CAD.     

Implantation of the 111In/Cd Probe as InO− Ion for Radioisotope Tracer Studies

A radioisotope ion implanter has been developed using a cesium-sputtering, negative ion source, which offers versatility and sustained operation. Employing the molecular ¹¹¹In¹⁶O⁻ ion, μCi activities of the radioisotope probe ¹¹¹In/Cd have been implanted into different material hosts. The implanted tracer activity has been shown to be sufficient for LTNO, NMRON and PAC. A new NMRON resonance for ¹¹¹InAg was observed at 75.08 MHz. In₂O₃ powder performed well as the radioisotope carrier in the ion source, with the ratio of radioisotope and parasitic ion current being typically 4 × 10⁻⁴.