No abstract

Roughness of nanoscopic dimensions can be used to selectively enhance the faradaic current of a sluggish reaction. Using this principle, we constructed mesoporous structures on the surfaces of pure platinum electrodes responding even more sensitively to glucose than to common interfering species, such as L-ascorbic acid and 4-acetamidophenol. Good sensitivities, as high as 9.6 microA cm(-2) mM(-1), were reproducibly observed in the presence of high concentration of chloride ion. The selectivities, sensitivities, and stabilities determined experimentally have demonstrated the potential of mesoporous platinum as a novel candidate for nonenzymatic glucose sensors.

Tau is required for the induction of long-term depression (LTD) of synaptic transmission in the hippocampus. Here we probe the role of tau in LTD, finding that an AMPA receptor internalization mechanism is impaired in tau KO mice, and that LTD causes specific phosphorylation at the serine 396 and 404 residues of tau. Surprisingly, we find that phosphorylation at serine 396, specifically, is critical for LTD but has no role in LTP. Finally, we show that tau KO mice exhibit deficits in spatial reversal learning. These findings underscore the physiological role for tau at the synapse and identify a behavioral correlate of its role in LTD.

Rheumatoid arthritis (RA) is a chronic inflammatory disease caused by both genetic and environmental factors. Smoking has been implicated as one of the most important extrinsic risk factors for its development and severity. Recent developments have shed light on the pathophysiology of RA in smokers, including oxidative stress, inflammation, autoantibody formation and epigenetic changes. The association of smoking and the development of RA have been demonstrated through epidemiologic studies, as well as through in vivo and animal models of RA. With increased use of biological agents in addition to standard disease-modifying antirheumatic drugs (DMARDs), there has been interest in how smoking affects drug response in RA treatment. Recent evidence suggests the response and drug survival in people treated with anti-tumour necrosis factor (anti-TNF) therapy is poorer in heavy smokers, and possible immunological mechanisms for this effect are presented in the current paper.

Breast cancer stem cells (BCSC) are resistant to conventional chemotherapy and radiotherapy, which may destroy tumor masses but not all BCSC that can mediate relapses. In the present study, we showed that the level of Wnt/b-catenin signaling in BCSC is relatively higher than in bulk tumor cells, contributing to a relatively higher level of therapeutic resistance. We designed a highly potent small-molecule inhibitor, CWP232228, which antagonizes binding of b-catenin to T-cell factor (TCF) in the nucleus. Notably, although CWP232228 inhibited the growth of both BCSC and bulk tumor cells by inhibiting b-catenin-mediated transcription, BCSC exhibited greater growth inhibition than bulk tumor cells. We also documented evidence of greater insulinlike growth factor-I (IGF-I) expression by BCSC than by bulk tumor cells and that CWP232228 attenuated IGF-I-mediated BCSC functions. These results suggested that the inhibitory effect of CWP232228 on BCSC growth might be achieved through the disruption of IGF-I activity. Taken together, our findings indicate that CWP232228 offers a candidate therapeutic agent for breast cancer that preferentially targets BCSC as well as bulk tumor cells.

Mesoporous electrodes provide an unusual opportunity to observe the dramatic transition of the electrochemical potential distribution in vicinity to mesoporous surfaces as the ionic strength varies. The experimental results were in accordance with what the classical Gouy-Chapman theory predicts on the basis of the correlation between Debye length (kappa-1) and the diameter of mesopores. Using the phenomenon that the electrochemically effective area of mesoporous electrode depends on the ionic strength, the faradaic current density of dioxygen reduction could be controlled by the electrolyte concentration.

Panax ginseng Meyer has been widely used as a tonic in traditional Korean, Chinese, and Japanese herbal medicines and in Western herbal preparations for thousands of years. In the past, ginseng was very rare and was considered to have mysterious powers. Today, the efficacy of drugs must be tested through well-designed clinical trials or meta-analyses, and ginseng is no exception. In the present review, we discuss the functions of ginseng described in historical documents and describe how these functions are taken into account in herbal prescriptions. We also discuss the findings of experimental pharmacological research on the functions of ginseng in ginseng-containing prescriptions and how these prescriptions have been applied in modern therapeutic interventions. The present review on the functions of ginseng in traditional prescriptions helps to demystify ginseng and, as a result, may contribute to expanding the use of ginseng or ginseng-containing prescriptions.

Geometric factors affecting the enhanced electrocatalysis on nanoporous Pt (L2-ePt) were examined by electrochemical methods and computer simulations. The experimental results revealed that the electrochemical enhancement of O2 and H2O2 does not come only from expansion of the active surface area (so-called roughness factor, f R) of L2-ePt. The presence of extra contribution was verified by the fact that significant enhancement in electrocatalytic reactions remained even after the effect of the f R was eliminated from the electrochemical redox behavior of O2 and H2O2 on L2-ePt electrodes. Not only the voltammetric observation but also potentiometric pH responses of L2-ePt suggested the presence of unique nanoporous effects other than the surface enlargement in regard to heterogeneous electrochemical reactions. L2-ePt showed near Nernstian behavior, faster response time, and less hysteresis even if the real surface area was smaller than that of flat Pt. Increased residence time near the electrode surface due to extremely confined space of nanoporous structure was proposed as possible origins and examined by the Monte Carlo simulations of simple model electrodes. The theoretical approaches indicated that long residence time of reactant at electrode surface by confinement effect of the nanoporous environment well accounted for the experimental results.