nsPEFs induce the ISR via ROS-mediated HRI activation

The integrated stress response (ISR) is one of the most important cytoprotective mechanisms and is integrated by phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α). Four eIF2α kinases, heme-regulated inhibitor (HRI), double-stranded RNA-dependent protein kinase (PKR), PKR-like endoplasmic reticulum kinase (PERK), and general control nonderepressible 2 (GCN2), are activated in response to several stress conditions. We previously reported that nanosecond pulsed electric fields (nsPEFs) are a potential therapeutic tool for ISR activation. In this study, we examined which eIF2α kinase is activated by nsPEF treatment. To assess the responsible eIF2α kinase, we used previously established eIF2α kinase quadruple knockout (4KO) and single eIF2α kinase-rescued 4KO mouse embryonic fibroblast (MEF) cells. nsPEFs 70 ns in duration with 30 kV/cm electric fields caused eIF2α phosphorylation in wild-type (WT) MEF cells. On the other hand, nsPEF-induced eIF2α phosphorylation was completely abolished in 4KO MEF cells and was recovered by HRI overexpression. CM-H2DCFDA staining showed that nsPEFs generated reactive oxygen species (ROS), which activated HRI. nsPEF-induced eIF2α phosphorylation was blocked by treatment with the ROS scavenger N-acetyl-L-cysteine (NAC). Our results indicate that the eIF2α kinase HRI is responsible for nsPEF-induced ISR activation and is activated by nsPEF-generated ROS

Upgrading of shielding for rare decay search in CANDLES

In the CANDLES experiment aiming to search for the very rare neutrino-less double beta decays (0νββ) using 48Ca, we introduced a new shielding system for high energy γ-rays from neutron captures in massive materials near the detector, in addition to the background reduction for 232Th decays in the 0νββ target of CaF2 crystals. The method of background reduction and the performance of newly installed shielding system are described

Doxorubicin Delivery Using pH and Redox Dual-Responsive Hollow Nanocapsules with a Cationic Electrostatic Barrier

For the delivery of doxorubicin (DOX), pH and redox dual responsive hollow nanocapsules were prepared through the stabilization of polymer vesicles, which spontaneously formed from polyamidoamine dendron-poly(l-lysine) (PAMAM dendron-PLL), by the introduction of disulfide (SS) bonds between PLLs. The SS-bonded nanocapsules exhibited a very slow release of DOX under an extracellular environment because the cationic PLL membrane acted as an electrostatic barrier against the protonated DOX molecules. However, increasing the glutathione concentration to the intracellular level facilitated the immediate release of DOX through the collapse of nanocapsules by the spontaneous cleavage of SS bonds. SS-bonded nanocapsules also escaped from the endosome by the buffering effect of PAMAM dendrons, and DOX delivery into the cytoplasm was achieved. Furthermore, DOX molecules delivered by SS-bonded nanocapsules exhibited an effective in vitro anticancer effect to HeLa cells

Pituitary apoplexy in a puberal child: A case report and review of the literature

Pituitary apoplexy is extremely rare in children and adolescents. A case of an 11-year-old pubertal female with complaints of intermittent holocranial headaches for 4 months, with progressive visual disturbances, who presented to the emergency department after the sudden onset of a thunderclap headache and acute deterioration in right eye vision, is presented. On laboratory investigation, her prolactin level was higher than 1000 ng/mL. Magnetic resonance imaging showed a sellar mass with suprasellar extension and characteristics of hemorrhage within it. The patient underwent emergency endoscopic endonasal transsphenoidal decompression of the tumor. Postoperatively, the patient recovered well, with improvement in right eye vision and a decrease in the prolactin level to normal. She was discharged on hormone replacement therapy. A literature review showed that only 21 patients with clinical pituitary apoplexy in the age group younger than 20 years have been reported since 1980 after the advent of CT; the present patient is the 22nd and the youngest patient with clinical pituitary apoplexy

Performance Evaluation of Parallel Processing Environment for Molecular Dynamics

Molecular dynamics (MD) is one of the popular applications in the research field of high performance computing. Since it requires large amount of CPU time basically proportional to the square of the number of atoms simulated, acceleration of MD is essential to simulation of large biomolecules like proteins. Therefore, parallelization of MD has been actively studied long time. However, most of the studies of parallel MD report modified or newly developed algorithms specialized to some computer architectures like vector-parallel supercomputer, and an end-user of MD software cannot implement them to popular MD software developed by other ones. In this study, we evaluated performance of four kinds of computer architectures: 1) vector-parallel supercomputer, 2) multi-processor machine with shared memory, 3) multi-processor machine with distributed memory, and 4) PC cluster. Various compiler options for parallelization and optimization were tested. Experimental results revealed that if MD software is not parallelized nor vectorized in source level, use of normal PC cluster with maximum use of optimization options in compilation is the best way