A Study on Uptake and Localization of Merocyanine 540 (MC540) in Murine Myeloid Leukemia Cells by Confocal Laser Scanning Microscopy (CLSM)

The intracellular localization of merocyanine 540 (MC540), a photosensitizer commonly used in the photo-inactivation of leukemia cells, was studied using confocal laser scanning microscopy. It was found for the first time that MC540 not only localized in the plasma membrane but also in the cytoplasm and the nuclear membrane of the murine myeloid leukemia M1 and WEHI 3B (JCS) cells. Exposure of MC540 treated leukemia cells to light under conditions that could cause photobleaching did not cause the redistribution of cell-bound MC540. Rapid localization of MC540 in the cytoplasm was observed 5 minutes after exposure of leukemia cell to MC540, indicating that MC540 could promptly be internalized by these two leukemia cell lines. In contrast, localization of MC540 was limited only to the plasma membrane of erythrocytes. These results suggest that the binding pattern of MC540 is cell type dependent and may be related to the efficacy of photosenitization in photodynamic therapy.     

Physical controls on directed virus assembly at nanoscale chemical templates

Viruses are attractive building blocks for nanoscale heterostructures, but little is understood about the physical principles governing their directed assembly. In situ force microscopy was used to investigate organization of Cowpea Mosaic Virus engineered to bind specifically and reversibly at nanoscale chemical templates with sub-30 nm features. Morphological evolution and assembly kinetics were measured as virus flux and inter-viral potential were varied. The resulting morphologies were similar to those of atomic-scale epitaxial systems, but the underlying thermodynamics was analogous to that of colloidal systems in confined geometries. The 1D templates biased the location of initial cluster formation, introduced asymmetric sticking probabilities, and drove 1D and 2D condensation at sub-critical volume fractions. The growth kinetics followed a t(1/2) law controlled by the slow diffusion of viruses. The ability of poly(ethylene glycol) (PEG) to induce the lateral expansion of virus clusters away from the 1D templates suggests a significant role for weak interactions.     

Arsenic trioxide targets Hsp60, triggering degradation of p53 and survivin

The mechanisms of action of arsenic trioxide (ATO), a clinically used drug for the treatment of acute promyelocytic leukemia (APL), have been actively studied mainly through characterization of individual putative protein targets. There appear to be no studies at a system level. Herein, we integrate metalloproteomics through a newly developed organoarsenic probe, As-AC (C₂₀H₁₇AsN₄O₃S₂) with quantitative proteomics, allowing 37 arsenic binding and 250 arsenic regulated proteins to be identified in NB4, a human APL cell line. Bioinformatics analysis reveals that ATO disrupts multiple physiological processes, in particular, chaperone-related protein folding and cellular response to stress. Furthermore, we discover heat shock protein 60 (Hsp60) as a vital target of ATO. Through biophysical and cell-based assays, we demonstrate that ATO binds to Hsp60, leading to abolishment of Hsp60 refolding capability. Significantly, the binding of ATO to Hsp60 disrupts the formation of Hsp60-p53 and Hsp60-survivin complexes, resulting in degradation of p53 and survivin. This study provides significant insights into the mechanism of action of ATO at a systemic perspective, and serves as guidance for the rational design of metal-based anticancer drugs.

A highly selective organoarsenic fluorescent probe As-AC and quantitative proteomics were employed to track arsenic-binding and regulating proteins in live leukemia cells. Hsp60 was validated as a new target of ATO.     

A tandem Heck-carbocyclization/Suzuki-coupling approach to the stereoselective syntheses of asymmetric 3,3-(diarylmethylene)indolinones

[reaction: see text] An efficient and versatile method for stereoselective synthesis of (E)-3,3-(diarylmethylene)indolinones by a palladium-catalyzed tandem Heck-carbocyclization/Suzuki-coupling sequence is presented. Factors influencing yield and selectivity, namely catalyst, coordinating ligand, and solvent, are detailed.     

On the blow-up of heat flow for conformal -harmonic maps

Using a comparison theorem, Chang, Ding, and Ye (1992) proved a finite time derivative blow-up for the heat flow of harmonic maps from (a unit ball in ) to (a unit sphere in ) under certain initial and boundary conditions. We generalize this result to the case of -harmonic map heat flow from to . In contrast to the previous case, our governing parabolic equation is quasilinear and degenerate. Technical issues such as the development of a new comparison theorem have to be resolved.

     

Experimental study of the radiative decays K+-->mu(+)nue(+)e(-) and K+-->e(+)nue(+)e(-)

Experiment 865 at the Brookhaven Alternating Gradient Synchrotron obtained 410 K+-->e(+)nue(+)e(-) and 2679 K+-->mu(+)nue(+)e(-) events including 10% and 19% background. The branching ratios were measured to be [2.48+/-0.14(stat)+/-0.14(syst)]x10(-8) (m(ee)>150 MeV) and (7.06+/-0.16+/-0.26)x10(-8) (m(ee)>145 MeV), respectively. Results for the decay form factors are presented.     

Relationship of hippocampus and amygdala to coronal MRI landmarks

Magnetic resonance imaging is playing an increasingly important role in the evaluation of the hippocampus, particularly in epilepsy, schizophrenia, and Alzheimer's dementia. Because of the complex configuration of the hippocampus, it is difficult to compare from patient to patient. We developed a system to allow comparison of the hippocampus on coronal images. We performed 34 magnetic resonance studies on 29 normal subjects. Ten anatomic landmarks were identified. These landmarks have a consistent 5-mm periodicity regardless of usual head flexion. In the second phase of our investigation, we showed that the amygdala, hippocampal head, hippocampal body, and hippocampal tail have a consistent relationship to the coronal magnetic resonance imaging landmarks.     

Critical behaviour of the ising model in a transverse field

A theory for the critical behaviour of the Ising model in a transverse field is presented. The existence of a central component in the spectral density of the longitudinal spin relaxation function is shown to result self-consistently from decay into itself and energy-fluctuation diffusion mode. Estimates of the various quantities are made forT nearT _c , the damping is seen to be temperature dependent. Our theory is appropriate for the caseΓ ～J whereΓ andJ are the magnitudes of the transverse field and the exchange interaction between the spins respectively. Its relevance to neutron scattering data on Van Vleck paramagnets is discussed.