The role of the SWI/SNF chromatin remodeling complex in pancreatic ductal adenocarcinoma

ATP-dependent chromatin remodeling complexes are a group of epigenetic regulators that can alter the assembly of nucleosomes and regulate the accessibility of transcription factors to DNA in order to modulate gene expression. One of these complexes, the SWI/SNF chromatin remodeling complex is mutated in more than 20% of human cancers. We have investigated the roles of the SWI/SNF complex in pancreatic ductal adenocarcinoma (PDA), which is the most lethal type of cancer. Here, we reviewed the recent literature regarding the role of the SWI/SNF complex in pancreatic tumorigenesis and current knowledge about therapeutic strategies targeting the SWI/SNF complex in PDA. The subunits of the SWI/SNF complex are mutated in 14% of human PDA. Recent studies have shown that they have context-dependent oncogenic or tumor-suppressive roles in pancreatic carcinogenesis. To target its tumor-suppressive properties, synthetic lethal strategies have recently been developed. In addition, their oncogenic properties could be novel therapeutic targets. The SWI/SNF subunits are potential therapeutic targets for PDA, and further understanding of the precise role of the SWI/SNF complex subunits in PDA is required for further development of novel strategies targeting SWI/SNF subunits against PDA

Role of a non-ionic surfactant in direct electron transfer-type bioelectrocatalysis by fructose dehydrogenase

A heterotrimeric membrane-bound fructose dehydrogenase (FDH) from Gluconobacter japonicus NBRC3260 contains FAD in subunit I and three heme C moieties in subunit II as the redox centers, and is one of the direct electron transfer (DET)-type redox enzymes. FDH-catalyzed current density of fructose oxidation at hydrophilic mercaptoethanol (MEtOH)-modified Au electrode is much larger than that at hydrophobic mercaptoethane (MEtn)-modified Au electrode. Addition of a non-ionic surfactant Triton® X-100 (1%) completely quenches the catalytic current at the MEtn-modified Au electrode, while only small competitive effect is observed at the MEtOH-modified Au electrode. Quartz crystal microbalance measurements support the adsorption of FDH and Triton® X-100 on both of the modified electrodes. We propose a model to explain the phenomenon as follows. The surfactant forms a monolayer on the hydrophobic MEtn-modified electrode with strong hydrophobic interaction, and FDH adsorbs on the surface of the surfactant monolayer. The monolayer inhibits the electron transfer from FDH to the electrode. On the other hand, the surfactant forms a bilayer on the hydrophilic MEtOH-modified electrode. The interaction between the surfactant bilayer and the hydrophilic electrode is relatively weak so that FDH replaces the surfactant and is embedded in the bilayer to communicate electrochemically with the hydrophilic electrode

Pathogenesis of Metastatic Calcification due to Hypercalcemia in Adult T-cell Leukemia-Lymphoma

Two cases of metastatic calcification due to hypercalcemia in adult T-cell leukemia-lymphoma (ATLL)associated with osteolytic change for activation of osteoclasts are reported. These cases of serum calcium were at a high level, 16.2 and 19.4mg/dl (normal range 8.4-10.4mg/dl). In our cases, metastatic calcification was detected in the tubules of kidneys, in the pulmonary alveolar septa of lungs, in the myocardium, in the muscular layer of stomach, in the lower portion of media of aorta, in the mucosa of stomach, in the tubules of testis, and in the liver by von Kossa\u27s silver nitrate method for calcium. Scattered osteoclasts were seen around the cortex of the bone. Roentgenograms showed osteolytic change in the skull, in the bilateral ulna, in the radius, in the humerus, in the tibia, and in the fibula. Therefore, hypercalcemia in ATLL may be caused by bone resorption-stimulating factors which promote the differeniation of osteocalast cells, resulting in calcium increases in the serum

Universal Non-Gaussian Velocity Distribution in Violent Gravitational Processes

We study the velocity distribution in spherical collapses and cluster-pair collisions by use of N-body simulations. Reflecting the violent gravitational processes, the velocity distribution of the resultant quasi-stationary state generally becomes non-Gaussian. Through the strong mixing of the violent process, there appears a universal non-Gaussian velocity distribution, which is a democratic (equal-weighted) superposition of many Gaussian distributions (DT distribution). This is deeply related with the local virial equilibrium and the linear mass-temperature relation which characterize the system. We show the robustness of this distribution function against various initial conditions which leads to the violent gravitational process. The DT distribution has a positive correlation with the energy fluctuation of the system. On the other hand, the coherent motion such as the radial motion in the spherical collapse and the rotation with the angular momentum suppress the appearance of the DT distribution.Comment: 11 pages, 19 eps figures, RevTex, submitted to PRE, Revised version, minor change