Plasma levels of amyloid beta proteins Abeta1-40 and Abeta1-42(43) are elevated in Down''s syndrome

We report a case of pseudosarcomatous fibromyxoid tumor of the bladder in a 23-year-old man with a 2 month history of painless gross hematuria, which was studied by biphasic contrast-enhanced helical CT. CT demonstrated a 2 cm diameter polypoid enhancing mass in the anterior bladder wall. The lesion measured 103 and 91 HU on early and delayed images, respectively. Increased contrast enhancement was attributed to a histologically highly vascular myxoid stroma.     

Native state kinetic stabilization as a strategy to ameliorate protein misfolding diseases: a focus on the transthyretin amyloidoses

Small molecule-mediated protein stabilization inside or outside of the cell is a promising strategy to treat protein misfolding/misassembly diseases. Herein we focus on the transthyretin (TTR) amyloidoses and demonstrate that preferential ligand binding to and stabilization of the native state over the dissociative transition state raises the kinetic barrier of dissociation (rate-limiting for amyloidogenesis), slowing and in many cases preventing TTR amyloid fibril formation. Since T119M-TTR subunit incorporation into tetramers otherwise composed of disease-associated subunits also imparts kinetic stability on the tetramer and ameliorates amyloidosis in humans, it is likely that small molecule-mediated native state kinetic stabilization will also alleviate TTR amyloidoses.     

Optical Faraday rotator using Ce-substituted fibrous YIG singlecrystal grown by floating-zone method with YAG laser heating

A new optical Faraday rotator using a fibrous Ce-substituted yttrium-iron-garnet (Ce:YIG) single crystal was developed. The fibrous Ce:YIG single crystal was successfully grown by the floating-zone method with infrared-assisted YAG laser heating at a fast growth rate. This crystal has a good quality and shows a better figure-of-merit for an optical Faraday rotator at wavelength λ=1.55 μm compared with commonly used Bi-substituted YIG films. Ce:YIG single crystals grown by our method are expected to reduce the cost of optical isolators     

Acute oral toxicity of microcystin-LR, a cyanobacterial hepatotoxin, in mice

Microcystin-LR (MCLR) is a hepatotoxic peptide produced by Microcystis aeruginosa, an alga found worldwide in reservoirs for drinking supply; however, acute oral toxicity of purified MCLR remains unknown. Therefore, a single dose of MCLR (more than 95% purity) ranging from 8.0 to 20.0 mg/kg body weight was orally given to female 6-week old BALB/c mice, and lethality and pathological changes were observed. Median lethal dose (LD50) of the orally given MCLR estimated by the up and down method was 10.9 mg/kg, which was 167 times higher than the i.p. LD50 value (65.4 microgram/kg by moving average method). Orally administrated toxin caused primarily hepatocellular injuries with characteristics of hemorrhage and necrosis. In situ end-labeling as well as electron microscopic observation revealed an induction of apoptotic cell death to hepatocytes. These results indicate the lethality of MCLR was much lower in oral dosage than by i.p. administration, but toxic effects are similar. In addition, apoptosis is considered one of major components in MCLR-induced hepatotoxicity.     

Biochemical Studies of Mitochondrial Malate: Quinone Oxidoreductase from Toxoplasma gondii

Toxoplasma gondii is a protozoan parasite that causes toxoplasmosis and infects almost one-third of the global human population. A lack of effective drugs and vaccines and the emergence of drug resistant parasites highlight the need for the development of new drugs. The mitochondrial electron transport chain (ETC) is an essential pathway for energy metabolism and the survival of T. gondii. In apicomplexan parasites, malate:quinone oxidoreductase (MQO) is a monotopic membrane protein belonging to the ETC and a key member of the tricarboxylic acid cycle, and has recently been suggested to play a role in the fumarate cycle, which is required for the cytosolic purine salvage pathway. In T. gondii, a putative MQO (TgMQO) is expressed in tachyzoite and bradyzoite stages and is considered to be a potential drug target since its orthologue is not conserved in mammalian hosts. As a first step towards the evaluation of TgMQO as a drug target candidate, in this study, we developed a new expression system for TgMQO in FN102(DE3)TAO, a strain deficient in respiratory cytochromes and dependent on an alternative oxidase. This system allowed, for the first time, the expression and purification of a mitochondrial MQO family enzyme, which was used for steady-state kinetics and substrate specificity analyses. Ferulenol, the only known MQO inhibitor, also inhibited TgMQO at IC₅₀ of 0.822 μM, and displayed different inhibition kinetics compared to Plasmodium falciparum MQO. Furthermore, our analysis indicated the presence of a third binding site for ferulenol that is distinct from the ubiquinone and malate sites.