Physiological roles of NOX/NADPH oxidase, the superoxide-generating enzyme

NADPH oxidase is a superoxide (O2•−)-generating enzyme first identified in phagocytes, essential for their bactericidal activities. Later, in non-phagocytes, production of O2•− was also demonstrated in an NADPH-dependent manner. In the last decade, several non-phagocyte-type NADPH oxidases have been identified. The catalytic subunit of these oxidases, NOX, constitutes the NOX family. There are five homologs in the family, NOX1 to NOX5, and two related enzymes, DUOX1 and DUOX2. Transgenic or gene-disrupted mice of the NOX family have also been established. NOX/DUOX proteins possess distinct features in the dependency on other components for their enzymatic activities, tissue distributions, and physiological functions. This review summarized the characteristics of the NOX family proteins, especially focused on their functions clarified through studies using gene-modified mice

Effect of Visual Information on Active Touch During Mirror Visual Feedback

Several studies have demonstrated that observation of a dummy or mirror-reflected hand being stroked or moving at the same time as the hidden hand evokes a feeling that the dummy hand is one’s own, such as the rubber hand illusion (RHI) and mirror visual feedback (MVF). Under these conditions, participants also report sensing the tactile stimulation applied to the fake hands, suggesting that tactile perception is modulated by visual information during the RHI and MVF. Previous studies have utilized passive stimulation conditions; however, active touch is more common in real-world settings. Therefore, we investigated whether active touch is also modulated by visual information during an MVF scenario. Twenty-three participants (13 men and 10 women; mean age ± SD: 21.6 ± 2.0 years) were required to touch a polyurethane pad with both hands synchronously, and estimate the hardness of the pad while observing the mirror reflection. When participants observed the mirror reflection of the other hand pushing a softer or harder pad, perceived hardness estimates were significantly biased toward softer or harder, respectively, even though the physical hardness of the pad remained constant. Furthermore, perceived hardness exhibited a strong correlation with finger displacement of the mirrored, but not hidden, hand. The modulatory effects on perceived hardness diminished when participants touched the pad with both hands asynchronously or with their eyes closed. Moreover, participants experienced ownership of the mirrored hand when they touched the pad with both hands synchronously but not asynchronously. These results indicate that hardness estimates were modulated by observation of the mirrored hand during synchronous touch conditions. The present study demonstrates that, similar to passive touch, active touch is also modulated by visual input

Cortical Regions Encoding Hardness Perception Modulated by Visual Information Identified by Functional Magnetic Resonance Imaging With Multivoxel Pattern Analysis

Recent studies have revealed that hardness perception is determined by visual information along with the haptic input. This study investigated the cortical regions involved in hardness perception modulated by visual information using functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis (MVPA). Twenty-two healthy participants were enrolled. They were required to place their left and right hands at the front and back, respectively, of a mirror attached to a platform placed above them while lying in a magnetic resonance scanner. In conditions SFT, MED, and HRD, one of three polyurethane foam pads of varying hardness (soft, medium, and hard, respectively) was presented to the left hand in a given trial, while only the medium pad was presented to the right hand in all trials. MED was defined as the control condition, because the visual and haptic information was congruent. During the scan, the participants were required to push the pad with the both hands while observing the reflection of the left hand and estimate the hardness of the pad perceived by the right (hidden) hand based on magnitude estimation. Behavioral results showed that the perceived hardness was significantly biased toward softer or harder in >73% of the trials in conditions SFT and HRD; we designated these trials as visually modulated (SFTvm and HRDvm, respectively). The accuracy map was calculated individually for each of the pair-wise comparisons of (SFTvm vs. MED), (HRDvm vs. MED), and (SFTvm vs. HRDvm) by a searchlight MVPA, and the cortical regions encoding the perceived hardness with visual modulation were identified by conjunction of the three accuracy maps in group analysis. The cluster was observed in the right sensory motor cortex, left anterior intraparietal sulcus (aIPS), bilateral parietal operculum (PO), and occipito-temporal cortex (OTC). Together with previous findings on such cortical regions, we conclude that the visual information of finger movements processed in the OTC may be integrated with haptic input in the left aIPS, and the subjective hardness perceived by the right hand with visual modulation may be processed in the cortical network between the left PO and aIPS

プロスタグランジンE受容体サブタイプEP[2]の構造と機能に関する研究

京都大学0048新制・課程博士博士(薬学)甲第7288号薬博第407号新制||薬||174(附属図書館)UT51-98-G217京都大学大学院薬学研究科薬学専攻(主査)教授 市川 厚, 教授 川嵜 敏祐, 教授 佐藤 公道学位規則第4条第1項該当Doctor of Pharmaceutical SciencesKyoto UniversityDFA

Activation of the Human MT Complex by Motion in Depth Induced by a Moving Cast Shadow

<div><p>A moving cast shadow is a powerful monocular depth cue for motion perception in depth. For example, when a cast shadow moves away from or toward an object in a two-dimensional plane, the object appears to move toward or away from the observer in depth, respectively, whereas the size and position of the object are constant. Although the cortical mechanisms underlying motion perception in depth by cast shadow are unknown, the human MT complex (hMT+) is likely involved in the process, as it is sensitive to motion in depth represented by binocular depth cues. In the present study, we examined this possibility by using a functional magnetic resonance imaging (fMRI) technique. First, we identified the cortical regions sensitive to the motion of a square in depth represented via binocular disparity. Consistent with previous studies, we observed significant activation in the bilateral hMT+, and defined functional regions of interest (ROIs) there. We then investigated the activity of the ROIs during observation of the following stimuli: 1) a central square that appeared to move back and forth via a moving cast shadow (mCS); 2) a segmented and scrambled cast shadow presented beside the square (sCS); and 3) no cast shadow (nCS). Participants perceived motion of the square in depth in the mCS condition only. The activity of the hMT+ was significantly higher in the mCS compared with the sCS and nCS conditions. Moreover, the hMT+ was activated equally in both hemispheres in the mCS condition, despite presentation of the cast shadow in the bottom-right quadrant of the stimulus. Perception of the square moving in depth across visual hemifields may be reflected in the bilateral activation of the hMT+. We concluded that the hMT+ is involved in motion perception in depth induced by moving cast shadow and by binocular disparity.</p></div

Results of the direct comparison.

<p>Activated regions revealed by contrasts mCS > nCS and sCS > nCS in the CS session are shown in the top and bottom sections of the figure, respectively.</p

Structural Requirements of Alkylglyceryl-l-Ascorbic Acid Derivatives for Melanogenesis Inhibitory Activity

l-Ascorbic acid has multifunctional benefits on skin aesthetics, including inhibition of melanin production, and is widely used in cosmetics. It, however, has low stability and poor skin penetration. We hypothesize that alkylglyceryl-l-ascorbic acid derivatives, highly stable vitamin C–alkylglycerol conjugates, would have similar anti-melanogenic activity with better stability and penetration. We test 28 alkylglyceryl-l-ascorbic acid derivatives (1–28) on theophylline-stimulated B16 melanoma 4A5 cells to determine if they inhibit melanogenesis and establish any structure–function relationships. Although not the most potent inhibitors, 3-O-(2,3-dihydroxypropyl)-2-O-hexyl-l-ascorbic acid (6, IC50 = 81.4 µM) and 2-O-(2,3-dihydroxypropyl)-3-O-hexyl-l-ascorbic acid (20, IC50 = 117 µM) are deemed the best candidate derivatives based on their inhibitory activities and low toxicities. These derivatives are also found to be more stable than l-ascorbic acid and to have favorable characteristics for skin penetration. The following structural requirements for inhibitory activity of alkylglyceryl-l-ascorbic acid derivatives are also determined: (i) alkylation of glyceryl-l-ascorbic acid is essential for inhibitory activity; (ii) the 3-O-alkyl-derivatives (2–14) exhibit stronger inhibitory activity than the corresponding 2-O-alkyl-derivatives (16–28); and (iii) derivatives with longer alkyl chains have stronger inhibitory activities. Mechanistically, our studies suggest that l-ascorbic acid derivatives exert their effects by suppressing the mRNA expression of tyrosinase and tyrosine-related protein-1