Analysis of the Anticipatory Behavior Formation Mechanism Induced by Methamphetamine Using a Single Hair.

While the suprachiasmatic nucleus (SCN) coordinates many daily rhythms, some circadian patterns of expression are controlled by SCN-independent systems. These include responses to daily methamphetamine (MAP) injections. Scheduled daily injections of MAP resulted in anticipatory activity, with an increase in locomotor activity immediately prior to the time of injection. The MAP-induced anticipatory behavior is associated with the induction and a phase advance in the expression rhythm of the clock gene Period1 (Per1). However, this unique formation mechanism of MAP-induced anticipatory behavior is not well understood. We recently developed a micro-photomultiplier tube (micro-PMT) system to detect a small amount of Per1 expression. In the present study, we used this system to measure the formation kinetics of MAP-induced anticipatory activity in a single whisker hair to reveal the underlying mechanism. Our results suggest that whisker hairs respond to daily MAP administration, and that Per1 expression is affected. We also found that elevated Per1 expression in a single whisker hair is associated with the occurrence of anticipatory behavior rhythm. The present results suggest that elevated Per1 expression in hairs might be a marker of anticipatory behavior formation.

Enhanced electrochemical hydrogen oxidation reaction and suppressed hydrogen peroxide generation properties on Pt/Ir(111) bimetallic surfaces.

Simultaneous accomplishment of high hydrogen oxidation reaction (HOR) activity and suppressed hydrogen peroxide (H2O2) generation is desired for anode catalysts of polymer electrolyte fuel cells. 0.3 monolayer-thick-Pt-deposited Ir(111) showed three-fold higher HOR activity than Pt(111) and suppressed H2O2 generation under the detection limit, providing insights for effective catalyst development.

Hydrogen peroxide generation and hydrogen oxidation reactions of vacuum-prepared Ru/Ir(111) bimetallic surfaces.

From the viewpoint of the application of Ir-Ru alloys for the anode of proton exchange membrane fuel cells (PEMFCs), hydrogen peroxide (H2O2) generation and the hydrogen oxidation reaction (HOR) properties of well-defined Ir-Ru bimetallic surfaces (Ru/Ir(111)) have been investigated using scanning electrochemical microscopy (SECM). Using thermal inter-diffusion of vacuum-deposited Ru and substrate Ir atoms, the topmost surface atomic ratios of Ru/Ir(111) were controlled via changing the substrate temperature (x) during the deposition of 1 monolayer (ML)-thick Ru. Low-energy ion scattering spectroscopy (LE-ISS) estimated the Ru/Ir ratio to be 1 : 1 (x = 673 K), 1 : 2 (x = 773 K), and 1 : 4 (x = 873 K). The H2O2 generation property of Ru/Ir(111) was similar to that of clean Ir(111) and under the detection limit in the potential region of 0.06-0.3 V, while clean Ru(0001) generated H2O2 in this potential region. The results suggest that the Ir sites contribute to the reduction of H2O2 intermediates generated at neighboring Ru sites. In contrast, the HOR activity of Ru/Ir(111) correlated with the probabilities of ensembles, such as Ir2 dimers and Ir3 trimers: the ensemble probabilities were calculated under the assumption of random solute Ir and Ru atoms at the topmost surfaces. Such a close correlation suggests that the Ir ensemble sites strongly contribute to the HOR. In conclusion, the Ir sites play a key role in the suppression of H2O2 generation and high HOR activity, which is essential for next-generation PEMFC anode catalysts.

Amino Acid Specificity of Ancestral Aminoacyl-tRNA Synthetase Prior to the Last Universal Common Ancestor Commonote commonote.

Extant organisms commonly use 20 amino acids in protein synthesis. In the translation system, aminoacyl-tRNA synthetase (ARS) selectively binds an amino acid and transfers it to the cognate tRNA. It is postulated that the amino acid repertoire of ARS expanded during the development of the translation system. In this study we generated composite phylogenetic trees for seven ARSs (SerRS, ProRS, ThrRS, GlyRS-1, HisRS, AspRS, and LysRS) which are thought to have diverged by gene duplication followed by mutation, before the evolution of the last universal common ancestor. The composite phylogenetic tree shows that the AspRS/LysRS branch diverged from the other five ARSs at the deepest node, with the GlyRS/HisRS branch and the other three ARSs (ThrRS, ProRS and SerRS) diverging at the second deepest node. ThrRS diverged next, and finally ProRS and SerRS diverged from each other. Based on the phylogenetic tree, sequences of the ancestral ARSs prior to the evolution of the last universal common ancestor were predicted. The amino acid specificity of each ancestral ARS was then postulated by comparison with amino acid recognition sites of ARSs of extant organisms. Our predictions demonstrate that ancestral ARSs had substantial specificity and that the number of amino acid types amino-acylated by proteinaceous ARSs was limited before the appearance of a fuller range of proteinaceous ARS species. From an assumption that 10 amino acid species are required for folding and function, proteinaceous ARS possibly evolved in a translation system composed of preexisting ribozyme ARSs, before the evolution of the last universal common ancestor.

Specific interactions between tau protein and curcumin derivatives: Molecular docking and ab initio molecular orbital simulations.

Alzheimer's disease (AD) is the most common neurodegenerative disorder in the world, and there is currently no potent medicine for the treatment of ADs. Curcumin, a primary chemical contained in the ancient Indian herb known as turmeric, has been extensively studied and shown to be effective in inhibiting the aggregations of amyloid-ß and tau proteins, both of which are observed in the brains of AD patients. In the present study, we focused on the tau protein and investigated its specific interactions with curcumin derivatives, using molecular simulations based on molecular docking, molecular mechanics and ab initio fragment molecular orbital calculations. Based on the results, we attempted to propose novel potent inhibitors against the tau protein aggregation. Our molecular simulations provide useful information for developing novel medicines for the treatment of ADs.

Specific interactions between 2-trans enoyl-acyl carrier protein reductase and its ligand: Protein-ligand docking and ab initio fragment molecular orbital calculations.

2-trans enoyl-acyl carrier protein reductase (InhA) has been identified as a promising target for the development of novel chemotherapy for tuberculosis. In the present study, a series of heteroaryl benzamide derivatives were selected as potent inhibitors against InhA, and their binding properties with InhA were investigated at atomic and electronic levels by ab initio molecular simulations based on protein-ligand docking, classical molecular mechanics optimizations and ab initio fragment molecular orbital (FMO) calculations. The results evaluated by FMO highlight some key interactions between InhA and the derivatives, indicating that the most potent derivative has strong hydrogen bonds with the Met98 side chain of InhA and strong electrostatic interactions with the nicotinamide adenine dinucleotide cofactor. These findings provide informative structural concepts for designing novel heteroaryl benzamide derivatives with higher binding affinity to InhA.