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Aminopeptidase B (APB, EC 3.4.11.6) preferentially hydrolyzes basic amino acids of synthetic substrates and requires a physiological concentration of chloride anions for optimal activity. Several amino acid residues of APB responsible for its enzymatic activity have been elucidated. In this study, we further searched for residues critical to its enzymatic activity, especially toward peptide substrates. APB residues Tyr409 (Y409) and Tyr414 (Y414), both of which were critical to its hydrolytic activity toward synthetic substrates, were predicted by molecular modeling to be involved in cleaving peptide substrates via its interaction with amino acids in the P1′ cleavage site. Using site-directed mutagenesis, several mutant APBs were prepared. In contrast to synthetic substrates, wild-type and Y409F/Y414F double mutant enzymes showed P1′-dependent cleavage of peptide substrates, indicating that both tyrosine residues were not indispensable for hydrolytic activity toward peptide substrates. Moreover, the Y409F/Y414F double mutant enzyme cleaved peptides with a Pro residue at the P1′ site, which is uncommon among the M1 family of aminopeptidases. These results suggested that Tyr409 and Tyr414 of APB play important roles in enzymatic function and characteristic properties of APB via proper formation of the S1′ site.

Several lines of evidence have suggested that visual self-recognition is supported by a special brain mechanism; however, its functional anatomy is of great controversy. We performed an event-related functional magnetic resonance imaging (fMRI) study to identify brain regions selectively involved in recognition of one's own face. We presented pictures of each subject's own face (SELF) and a prelearned face of an unfamiliar person (CONT), as well as two personally familiar faces with high and low familiarity (HIGH and LOW, respectively) to test selectivity of activation to the SELF face. Compared with the CONT face, activation selective to the SELF face was observed in the right occipito-temporo-parietal junction and frontal operculum, as well as in the left fusiform gyrus. On the contrary, the temporoparietal junction in both the hemispheres and the left anterior temporal cortex, which were activated during recognition of HIGH and/or LOW faces, were not activated during recognition of the SELF face. The results confirmed the partial distinction of the brain mechanism involved in recognition of personally familiar faces and that in recognition of one's own face. The right occipito-temporo-parietal junction and frontal operculum appear to compose a network processing motion–action contingency, a role of which in visual self-recognition has been suggested in previous behavioral studies. Activation of the left fusiform gyrus selective to one's own face was consistent with the results of two previous functional imaging studies and a neuropsychological report, possibly suggesting its relationship with lexical processing.

In this paper, a new procedure is presented which allows the estimation of the states and parameters of the hemodynamic approach from blood oxygenation level dependent (BOLD) responses. The proposed method constitutes an alternative to the recently proposed Friston [Neuroimage 16 (2002) 513] method and has some advantages over it. The procedure is based on recent groundbreaking time series analysis techniques that have been, in this case, adopted to characterize hemodynamic responses in functional magnetic resonance imaging (fMRI). This work represents a fundamental improvement over existing approaches to system identification using nonlinear hemodynamic models and is important for three reasons. First, our model includes physiological noise. Previous models have been based upon ordinary differential equations that only allow for noise or error to enter at the level of observation. Secondly, by using the innovation method and the local linearization filter, not only the parameters, but also the underlying states of the system generating responses can be estimated. These states can include things like a flow-inducing signal triggered by neuronal activation, de-oxyhemoglobine, cerebral blood flow and volume. Finally, radial basis functions have been introduced as a parametric model to represent arbitrary temporal input sequences in the hemodynamic approach, which could be essential to understanding those brain areas indirectly related to the stimulus. Hence, thirdly, by inferring about the radial basis parameters, we are able to perform a blind deconvolution, which permits both the reconstruction of the dynamics of the most likely hemodynamic states and also, to implicitly reconstruct the underlying synaptic dynamics, induced experimentally, which caused these states variations. From this study, we conclude that in spite of the utility of the standard discrete convolution approach used in statistical parametric maps (SPM), nonlinear BOLD phenomena and unspecific input temporal sequences must be included in the fMRI analysis.

Personally familiar people are likely to be represented more richly in episodic, emotional, and behavioral contexts than famous people, who are usually represented predominantly in semantic context. To reveal cortical mechanisms supporting this differential person representation, we compared cortical activation during name recognition tasks between personally familiar and famous names, using an event-related functional magnetic resonance imaging (fMRI). Normal subjects performed familiar- or unfamiliar-name detection tasks during visual presentation of personally familiar (Personal), famous (Famous), and unfamiliar (Unfamiliar) names. The bilateral temporal poles and anterolateral temporal cortices, as well as the left temporoparietal junction, were activated in the contrasts Personal–Unfamiliar and Famous–Unfamiliar to a similar extent. The bilateral occipitotemporoparietal junctions, precuneus, and posterior cingulate cortex showed activation in the contrasts Personal–Unfamiliar and Personal–Famous. Together with previous findings, differential activation in the occipitotemporoparietal junction, precuneus, and posterior cingulate cortex between personally familiar and famous names is considered to reflect differential person representation. The similar extent of activation for personally familiar and famous names in the temporal pole and anterolateral temporal cortex is consistent with the associative role of the anterior temporal cortex in person identification, which has been conceptualized as a person identity node in many models of person identification. The left temporoparietal junction was considered to process familiar written names. The results illustrated the neural correlates of the person representation as a network of discrete regions in the bilateral posterior cortices, with the anterior temporal cortices having a unique associative role.

An event-related fMRI technique was used to assess neural responses to financial reward and penalty during a simple gambling task. We attempted to determine whether brain activities are dependent on the unique context of an event sequence. Thirty-six healthy volunteers participated in the study. The task was to guess the color of the suit of a card on each trial and to respond by pressing a button. Every correct response (“win”) and incorrect response (“loss”) was associated with financial reward and penalty, respectively. The magnitude of reward or penalty in each trial did not change; however, the subjects' self-reported emotional arousal was significantly higher for the events of “the fourth win of four wins in a row” and “the fourth loss of four losses in a row.” We also found that the bilateral anterior cingulate and medial prefrontal cortices were specifically activated when the subjects experienced “the fourth win of four wins in a row” and “the fourth loss of four losses in a row. ”When the subjects experienced “a win following four losses in a row” or “a loss following four wins in a row, ”the right dorsolateral prefrontal cortex was specifically activated. Our data indicate that there exist brain activities associated with the event-sequence context in which abstract reward or penalty is received. These context-dependent activities appear to be crucial for adapting oneself to new circumstances and may account for clinical symptoms of various mental illnesses in which dysfunction of these regions has been reported.

The human tongue is so sensitive and dexterous that spatial representations of the inside of the oral cavity for the tongue movement are naturally expected to exist. In the present study, we examined the brain activity associated with spatial processing during tongue movements using a functional magnetic resonance imaging technique. Twenty-four normal subjects participated in the study, which consisted of a periodic series of three blocks; resting of the tongue, tongue movement (pressing the inside of a tooth with the tip of the tongue), and tongue retraction. The cerebral fields of activation during the tongue movement to the left and right side relative to those during rest were found in the primary sensorimotor area and supplementary motor area bilaterally, and in the left inferior parietal lobule (IPL). The activation areas during the tongue retraction relative to those during rest were almost the same, except that activation in the left IPL was not observed. The fields of activation during tongue movement to the left and right side relative to those during tongue retraction were found bilaterally in the dorsal premotor area, superior parietal lobule (SPL), and the IPL. The results indicate that the bilateral SPL and IPL were specifically involved in the processing for human tongue movement. Although no significant laterality was observed, the left parietal area tended to show greater activation in statistical values and area than the right parietal area, thus indicating the possibility that this processing for human tongue movement is related to that for language.

The purpose of this study was to investigate human brain activity during the reading of ancient Japanese texts using functional magnetic resonance imaging. Thirty right-handed normal Japanese subjects performed two reading tasks: covert reading of (1) ancient and (2) modern Japanese text. Common areas are activated during both tasks. Activity in the left inferior frontal cortices increased during the reading of ancient Japanese text compared with the reading of modern Japanese text, whereas occipital activity increased during the reading of modern Japanese text. Our results indicate that ancient Japanese language may be processed as a foreign language.

One of the important roles of the prefrontal cortex is inhibition of movement. We applied an event-related functional magnetic resonance imaging (fMRI) technique to observe changes in fMRI signals of the entire brain during a GO/NO-GO task to identify the functional fields activated in relation to the NO-GO decision. Eleven normal subjects participated in the study, which consisted of a random series of 30 GO and 30 NO-GO trials. The subjects were instructed to press a mouse button immediately after the GO signal was presented. However, they were instructed not to move when the NO-GO signal was presented. We detected significant changes in MR signals in relation to the preparation phases, GO responses, and NO-GO responses. The activation fields related to the NO-GO responses were located in the bilateral middle frontal cortices, left dorsal premotor area, left posterior intraparietal cortices, and right occipitotemporal area. The fields of activation in relation to the GO responses were found in the left primary sensorimotor, right cerebellar anterior lobule, bilateral thalamus, and the area from the anterior cingulate to the supplementary motor area (SMA). Brain activations related to the preparation phases were identified in the left dorsal premotor, left lateral occipital, right ventral premotor, right fusiform, and the area from the anterior cingulate to the SMA. The results indicate that brain networks consisting of the bilateral prefrontal, intraparietal, and occipitotemporal cortices may play an important role in executing a NO-GO response.