Identification of mutagenic transformation products generated during oxidation of 3-methyl-4-nitrophenol solutions by orbitrap tandem mass spectrometry and quantitative structure activity relationship analyses

We used Ames assays to investigate the effects of ozonation (designated O-3), ozonation followed by chlorination (O-3/Cl), an advanced oxidation process (AOP, UV/H2O2), and AOP followed by chlorination (AOP/Cl) on the mutagenicity of solutions of 3-methy1-4-nitrophenol (3M4NP), a major environmental degradation product of the organopliosphorus insecticide fenitrothion. Whereas O-3 did not induce mutagenicity, O-3/Cl, AOP, and AOP/Cl converted 3M4NP into mutagenic transformation products (TPs). Using liquid chromatography mass spectrometry, we detected a total of 138 peaks in the solutions subjected to O-3/Cl, AOP, and AOP/Cl. To elucidate the TPs responsible for the observed mutagenicity, we performed simple regression analyses of the relationship between the area of each peak and the observed mutagenicity of samples withdrawn periodically during each oxidation process. The area of each of 10 peaks was found to be positively correlated (r(2) >= 0.8) with the observed mutagenicity, suggesting that the TPs corresponding to these peaks contributed to the mutagenicity. After taking into account the consistency of mutagenicity induction by the oxidation processes and analyzing the peaks by tandem mass spectrometry, we identified 3 TPs, corresponding to 6 peaks, as candidate mutagens. These TPs were assessed by means of 4 quantitative structure activity relationship (QSAR) models, and all 3 were predicted to be mutagenic by at least one model. This result was consistent with our assumption that these TPs were mutagens. Ames assays of an authentic sample of one of the 3 TPs revealed that it did not contribute to the mutagenicity. This left 3-methoxy-4-nitrophenol and 2-[(E)-[(2,5-dihydroxyphenyl) methylidene]amino]-5-dihydroxybenzaldehyde on the list of mutagens suspected of contributing to the mutagenicity induced by AOP. No TPs were identified as candidate mutagens responsible for the mutagenicity induced by O-3/Cl and AOP/Cl

Impact of Audio-Visual Asynchrony on Lip-Reading Effects -Neuromagnetic and Psychophysical Study-

<div><p>The effects of asynchrony between audio and visual (A/V) stimuli on the N100m responses of magnetoencephalography in the left hemisphere were compared with those on the psychophysical responses in 11 participants. The latency and amplitude of N100m were significantly shortened and reduced in the left hemisphere by the presentation of visual speech as long as the temporal asynchrony between A/V stimuli was within 100 ms, but were not significantly affected with audio lags of -500 and +500 ms. However, some small effects were still preserved on average with audio lags of 500 ms, suggesting similar asymmetry of the temporal window to that observed in psychophysical measurements, which tended to be more robust (wider) for audio lags; i.e., the pattern of visual-speech effects as a function of A/V lag observed in the N100m in the left hemisphere grossly resembled that in psychophysical measurements on average, although the individual responses were somewhat varied. The present results suggest that the basic configuration of the temporal window of visual effects on auditory-speech perception could be observed from the early auditory processing stage.</p></div

Typical example of the effects of visual speech (simultaneous [A/V offset = 0] condition) on the waveforms of AEFs observed in the left hemisphere.

<p><b>a</b>: Superimposed waveforms recorded from all sensors located in the left hemisphere for control condition (/ge/ sound with visual noise: black dotted lines) and for A/V 0 condition (/ge/ sound presented with visual /be/ without no lag: red line). <b>b</b>: Root mean square (RMS) waveforms calculated from all sensors in the left hemisphere for control condition (/ge/ sound with visual noise: black dotted lines) and for A/V 0 condition (/ge/ sound presented with visual /be/ without no lag: red line).</p

Audio-visual (A/V) stimuli used in the present study.

<p>Monosyllabic sound /be/ spoken by a Japanese male speaker was presented under six different visual conditions: 1) control: visual noise created by applying a strong Gaussian filter of a PC software (Adobe^® Photoshop) to a still image of the speaker’s face, and moving image of the same speaker’s face uttering /ge/ (incongruent visual stimuli known to evoke McGurk effect); 2) with synchronous conditions (no A/V lag) (A/V 0); 3) with +500 ms audio lag (A/V +500); 4) with +100 ms audio lag (A/V +100); 5) with -100 ms audio lag or +100 ms audio lead (A/V -100); and 6) with -500 ms audio lag or +500 ms audio lead (A/V -500). Each visual stimulus was prepared as a video clip with duration of 3 s. Audio stimulus started 1400 ms after the beginning of the visual stimulus and lasted for approximately 180 ms under the A/V 0 as well as control conditions (A/V noise). The presentation timing of audio stimuli were preceded or delayed 100 and 500 ms under A/V +/-100 and +/-500 ms conditions, respectively. The still images of visual stimuli at the timing points of -500 ms, -300 ms, -100 ms, 0 ms (at the onset of utterance), +100 ms, +300 ms, and +500 ms after the onset of utterance represent the moving images of uttering /ge/ (these face images in Fig 1 were treated with a digital filter except for the area around the mouth, so that the individual can not be identified). The movement of the speaker’s mouth started just before the time point -300 ms (300 ms before the onset of utterance) and ended just after the time point +300 ms (300 ms after the onset of utterance).</p

Impact of Audio-Visual Asynchrony on Lip-Reading Effects -Neuromagnetic and Psychophysical Study- - Fig 5

<p><b>Effects of visual speech on latency (A) and amplitude (B) of N100m in the left hemisphere.</b> Small dots indicate individual data. Average and standard error values are represented by filled circles and bars, respectively. In visual effects on both N100m latency and amplitude, significant effects (shortening of N100m latency and reduction of N100m amplitude) compared with the control condition (visual noise) are observed with temporal asynchrony within 100 ms. On the other hand, no significant effects could not be obtained with -500 ms audio lag. However, some effects (although not significant on average) were still observed in subjects with +500 ms audio lag on average. Statistical significance of differences was determined by one-way repeated measures analysis of variance with Bonferroni post-hoc analysis. Asterisks indicate significant differences.</p

Psychophysical McGurk responses as a function of A/V offset.

<p>McGurk response rates are plotted with respect to each A/V condition. Small dots indicate individual data. Average and standard error values are represented by filled circles and bars, respectively. High fusion response rates were observed in response to synchronous A/V stimuli if the temporal asynchrony was within 100 ms. On the other hand, the fusion rate was remarkably reduced with temporal asynchrony of 500 ms, but the temporal window tended to be more robust (wider) for audio lags (asymmetry between audio vs. visual lags). Statistical significance of differences in positive fusion responses between each A/V offset condition and the control condition was determined by one-way repeated measures analysis of variance with Bonferroni post-hoc analysis. Asterisks indicate significant increase of fusion responses compared to the control condition.</p

Typical examples of the effects of A/V lag on RMS waveforms of AEFs.

<p>Typical examples of the RMS waveforms are shown with respect to each A/V lag (AEFs under visual noise are indicated using black dotted lines), divided into each hemisphere (see "Visual effects on N100m" for further details).</p