Propagation direction of natural mechanical oscillations in the biceps brachii muscle during voluntary contraction

The aim of the study was to determine the directionality of the coupling of mechanical vibrations across the biceps brachii muscle at different frequencies of interest during voluntary contraction. The vibrations that are naturally generated by skeletal muscles were recorded by a two-dimensional array of skin mounted accelerometers over the biceps brachii muscle (surface mechanomyogram, S-MMG) during voluntary isometric contractions in ten healthy young men. As a measure of the similarity of vibration between a given pair of accelerometers, the spatial coherence of S-MMG at low (f < 25 Hz) and high (f > 25 Hz) frequency bands were investigated to determine if the coupling of the natural mechanical vibrations were due to the different physiological muscle activity at low and high frequencies. In both frequency bands, spatial coherence values for sensor pairs aligned longitudinally along the proximal to distal ends of the biceps were significantly higher compared with those for the sensor pairs oriented perpendicular to the muscle fibers. This difference was more evident at the higher frequency band. The findings indicated that coherent mechanical oscillations mainly propagated along the longitudinal direction of the biceps brachii muscle fibers at high frequencies (f > 25 Hz).     

Optical imaging of plastic changes induced by fear conditioning in the auditory cortex

The plastic changes in the auditory cortex induced by a fear conditioning, through pairing a sound (CS) with an electric foot-shock (US), were investigated using an optical recording method with voltage sensitive dye, RH795. In order to investigate the effects of association learning, optical signals in the auditory cortex in response to CS (12 kHz pure tone) and non-CS (4, 8, 16 kHz pure tone) were recorded before and after normal and sham conditioning. As a result, the response area to CS enlarged only in the conditioning group after the conditioning. Additionally, the rise time constant of the auditory response to CS significantly decreased and the relative peak value and the decay time constant of the auditory response to CS significantly increased after the conditioning. This study introduces an optical approach to the investigation of fear conditioning, representational plasticity, and the cholinergic system. The findings are synthesized in a model of the synaptic mechanisms that underlie cortical plasticity.     

Macrophage-capping protein as a tissue biomarker for prediction of response to gemcitabine treatment and prognosis in cholangiocarcinoma

Cholangiocarcinoma is one of the deadliest malignancies worldwide. Recent studies reported that treatment with gemcitabine was effective in prolonging survival. However, as the treatment only benefited a limited subset of patients, selection of patients before treatment is required. To discover biomarkers predictive of the response to gemcitabine treatment in cholangiocarcinoma, we examined the proteome of three types of material resource; ten cell lines, nine xenografts and nine surgically resected primary tumors from patients who exhibited different response to gemcitabine treatment. Two-dimensional difference gel electrophoresis generated quantitative protein expression profiles including 3571 protein spots. We detected 172 protein spots with significant correlation with response to gemcitabine treatment. All proteins corresponding to these 172 protein spots were identified by mass spectrometry. We found that the macrophage-capping protein (CapG) was associated with response to gemcitabin treatment in all three types of material source. Immunohistochemical validation in an additional set of 196 cholangiocarcinoma cases revealed that CapG expression was associated with lymphatic invasion status and overall survival. Multivariate analysis showed that CapG protein expression was an independent prognostic factor for overall survival. In conclusion, CapG was identified as a novel candidate biomarker to predict response to gemcitabine treatment and survival in cholangiocarcinoma.     

Pressure-tuning FT-IR spectroscopic study on the helix–coil transition of Ala-rich oligopeptide in aqueous solution

We investigated the effect of pressure on the helix–coil transition of an Ala-rich peptide (AK16: YGAAKAAAAKAAAAKA-NH₂) in aqueous solution by FT-IR spectroscopy. The spectra of the amide I' region of AK16 in aqueous solution was decomposed into some component bands using a curve fitting method. The peak at around 1635 cm ^?1 corresponding to the solvent exposed α-helix conformer increases with increasing pressures, while the peak at around 1655 cm ^?1 corresponding to the random coil conformer decreases. From the pressure dependence of the band intensities, we determined the volume change from the α-helix to random coil conformers of AK16 to be + 10.5 ± 0.3 cm³/mol. The positive volume change is different from the negative volume change generally observed in the pressure denaturation of proteins.     

Cross talk between germ cells and gonadal somatic cells is critical for sex differentiation of the gonads in the teleost fish, medaka (Oryzias latipes)

To evaluate the possible role of germ cells on sex differentiation of the gonads in vertebrates, the teleost fish, medaka ( Oryzias latipes ), was used to generate a gonad without germ cells. The germ cell-deficient medaka reveals multiple effects of germ cells on the process of sex differentiation. The previously isolated mutant medaka, hotei , with the excessive number of germ cells may support the contention that the proliferation of germ cells is related to feminization of the gonad. Futhermore, we show that two modes of proliferation for either maintenance of germ cells or commitment to gametogenesis are important components of the sex differentiation of medaka developing gonads. An intimate cross talk between germ cells and gonadal somatic cells during the sex differentiation will be discussed.     

Inhibition of autophosphorylation of epidermal growth factor receptor by a small peptide not employing an ATP-competitive mechanism

Previously we found that short peptides surrounding major autophosphorylation sites of EGFR (VPEY(1068)INQ, DY(1148)QQD, and ENAEY(1173)LR) suppress phosphorylation of purified EGFR to 30-50% at 4000 microM. In an attempt to improve potencies of the peptides, we modified the sequences by substituting various amino acids for tyrosine or by substituting Gln and Asn for Glu and Asp, respectively. Among the modified peptides, Asp/Asn- and Glu/Gln-substitution in DYQQD (NYQQN) and ENAEYLR (QNAQYLR), respectively, improved inhibitory potencies. The inhibitory potency of NYQQN was not affected by the concentration of ATP, while that of QNAQYLR was affected. Docking simulations showed different mechanisms of inhibition for the peptides: inhibition by binding to the ATP-binding site (QNAQYLR) and inhibition by binding to a region surrounded by alphaC, the activation loop, and the catalytic loop and interfering with the catalytic reaction (NYQQN). The inhibitory potency of NYQQN for insulin receptor drastically decreased, whereas QNAQYLR inhibited autophosphorylation of insulin receptor as well as EGFR. In conclusion, NYQQN is not an ATP-competitive inhibitor and the binding site of this peptide appears to be novel as a tyrosine kinase inhibitor. NYQQN could be a promising seed for the development of anti-cancer drugs having specificity for EGFR.     

Post-synaptic action of morphine on glutamatergic neuronal transmission related to the descending antinociceptive pathway in the rat thalamus

Morphine is a prototypical μ-opioid receptor (MOR) agonist, and can directly inhibit pain transmission at both spinal and supraspinal levels. In the present study, we investigated the properties of thalamic neurons in an opioid-sensitive pain-modulating circuit. Application of morphine to cultured thalamic neurons evoked a potentiation of glutamate-induced peak currents, which was blocked by the MOR antagonist. Application of the protein kinase C inhibitor chelerythrine significantly inhibited the morphine-evoked enhancement of glutamate-induced currents. Immunoreactivity for MOR was observed with high density in the habenular nucleus (Hb) of the thalamus in rats, which was clearly co-localized with NMDA receptor subunit 1 (NRI). In this study, we show that microinjection of morphine into the Hb produced a dose-dependent increase in the tail-flick latency and enhanced the antinociceptive effect induced by the intra-Hb injection of glutamate. When fluoro-gold (FG) was used as a retrograde tracer, we found that FG-labeled neurons in the Hb after the microinjection of FG into the periaqueductal gray expressed both MOR and NR1. The present data suggest that the stimulation of MOR in the Hb may be involved in activation of the descending antinociceptive pathway through glutamatergic neurotransmission via the NMDA receptor.