Facial expressions affect the memory of facial colors.

Facial color influences the perception of facial expressions, and emotional expressions bias how facial color is remembered. However, it remains unclear whether facial expressions affect daily facial color memory. The memory color effect demonstrates that knowledge about typical colors affects the perception of the actual color of given objects. To investigate the effect of facial color memory, we examined whether the memory color effect for faces varies depending on facial expression. We calculated the subjective achromatic point of the facial expression image stimulus and compared the degree to which it was shifted from the actual achromatic point between facial expression conditions. We hypothesized that if the memory of facial color is influenced by the facial expression color (e.g., anger is a warm color, fear is a cold color), then the subjective achromatic point would vary with facial expression. In Experiment 1, we recruited 13 participants who adjusted the color of facial expression stimuli (anger, neutral, and fear) and a banana stimulus to be achromatic. No significant differences in the subjective achromatic point between facial expressions were observed. Subsequently, we conducted Experiment 2 with 23 participants because Experiment 1 did not account for the sensitivity to color changes on the face; humans perceive greater color differences in faces than in non-faces. Participants selected which facial color they believed the expression stimulus appeared to be, choosing one of two options provided to them. The results indicated that the subjective achromatic points of anger and fear faces significantly shifted toward the opposite color direction compared with neutral faces in the brief presentation condition. This research suggests that the memory color of faces differs depending on facial expressions and supports the idea that the perception of emotional expressions can bias facial color memory.

Chronic ingestion of soy peptide supplementation reduces aggressive behavior and abnormal fear memory caused by juvenile social isolation.

Juvenile loneliness is a risk factor for psychopathology in later life. Deprivation of early social experience due to peer rejection has a detrimental impact on emotional and cognitive brain function in adulthood. Accumulating evidence indicates that soy peptides have many positive effects on higher brain function in rodents and humans. However, the effects of soy peptide use on juvenile social isolation are unknown. Here, we demonstrated that soy peptides reduced the deterioration of behavioral and cellular functions resulting from juvenile socially-isolated rearing. We found that prolonged social isolation post-weaning in male C57BL/6J mice resulted in higher aggression and impulsivity and fear memory deficits at 7 weeks of age, and that these behavioral abnormalities, except impulsivity, were mitigated by ingestion of soy peptides. Furthermore, we found that daily intake of soy peptides caused upregulation of postsynaptic density 95 in the medial prefrontal cortex and phosphorylation of the cyclic adenosine monophosphate response element binding protein in the hippocampus of socially isolated mice, increased phosphorylation of the adenosine monophosphate-activated protein kinase in the hippocampus, and altered the microbiota composition. These results suggest that soy peptides have protective effects against juvenile social isolation-induced behavioral deficits via synaptic maturation and cellular functionalization.

Glossiness perception and its pupillary response.

Recent studies have revealed that pupillary response changes depend on perceptual factors such as subjective brightness caused by optical illusions and luminance. However, the manner in which the perceptual factor that is derived from the glossiness perception of object surfaces affects the pupillary response remains unclear. We investigated the relationship between the glossiness perception and pupillary response through a glossiness rating experiment that included recording the pupil diameter. We prepared general object images (original) and randomized images (shuffled) that comprised the same images with randomized small square regions as stimuli. The image features were controlled by matching the luminance histogram. The observers were asked to rate the perceived glossiness of the stimuli presented for 3,000 ms and the changes in their pupil diameters were recorded. Images with higher glossiness ratings constricted the pupil size more than those with lower glossiness ratings at the peak constriction of the pupillary responses during the stimulus duration. The linear mixed-effects model demonstrated that the glossiness rating, image category (original/shuffled), variance of the luminance histogram, and stimulus area were most effective in predicting the pupillary responses. These results suggest that the illusory brightness obtained by the image regions of high-glossiness objects, such as specular highlights, induce pupil constriction.

The effect of facial colour on implicit facial expressions.

Humans recognise reddish-coloured faces as angry. However, does facial colour also affect "implicit" facial expression perception of which humans are not explicitly aware? In this study, we investigated the effects of facial colour on implicit facial expression perception. The experimental stimuli were "hybrid faces", in which the low-frequency component of the neutral facial expression image was replaced with the low-frequency component of the facial expression image of happiness or anger. In Experiment 1, we confirmed that the hybrid face stimuli were perceived as neutral and, therefore, supported implicit facial expression perception. In Experiment 2, the hybrid face stimuli were adjusted to natural and reddish facial colours, and their friendliness ratings were compared. The results showed that the expression of happiness was rated as more friendly than the expression of anger. In addition, the expression of happiness was rated as friendlier when the low-frequency happy component was red, but the friendliness rating of the expression of anger did not change when it was presented in red. In Experiment 3, we affirmed the implicit facial expression perception even in reddish colours. These results suggest that facial colour modulates the perception of implicit facial expressions in hybrid facial stimuli.

Elucidation of the mechanisms underlying tumor aggravation by the activation of stress-related neurons in the paraventricular nucleus of the hypothalamus.

A growing body of evidence suggests that excess stress could aggravate tumor progression. The paraventricular nucleus (PVN) of the hypothalamus plays an important role in the adaptation to stress because the hypothalamic-pituitary-adrenal (HPA) axis can be activated by inducing the release of corticotropin-releasing hormone (CRH) from the PVN. In this study, we used pharmacogenetic techniques to investigate whether concomitant activation of CRHPVN neurons could directly contribute to tumor progression. Tumor growth was significantly promoted by repeated activation of CRHPVN neurons, which was followed by an increase in the plasma levels of corticosterone. Consistent with these results, chronic administration of glucocorticoids induced tumor progression. Under the concomitant activation of CRHPVN neurons, the number of cytotoxic CD8+ T cells in the tumor microenvironment was dramatically decreased, and the mRNA expression levels of hypoxia inducible factor 1 subunit α (HIF1α), glucocorticoid receptor (GR) and Tsc22d3 were upregulated in inhibitory lymphocytes, tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). Furthermore, the mRNA levels of various kinds of driver molecules related to tumor progression and tumor metastasis were prominently elevated in cancer cells by concomitant activation of CRHPVN neurons. These findings suggest that repeated activation of the PVN-CRHergic system may aggravate tumor growth through a central-peripheral-associated tumor immune system.

Hollow cylindrical linear stator vibrator using a traveling wave of longitudinal axisymmetric vibration mode.

Ultrasonic motors (USMs) are expected to be used in special environments: high magnetic field environments and space environments, which require lightweight and multiple degrees of freedom. However, when used as linear ultrasonic motors (LUSMs), a linear guide and a preload mechanism are required, complicating the structure. In the present paper, a hollow cylindrical linear stator without an extra linear guide has been considered. The stator consists of a metal pipe and two piezoelectric (PZT) tubes installed at both ends of the metal pipe. Their connected parts are tapered for the first longitudinal axisymmetric vibration mode of the cylinder, namely L(0,1) mode excitation, and the metal pipe is subjected to radial strain. The vibration of the stator is assumed to be one-dimensional and is modeled by an electromechanical equivalent circuit. The principle that the traveling wave is formed on the metal pipe by dual-PZT-tube phase difference excitation was clarified. Finite element analysis and some measurements were conducted to confirm that the theory was consistent. The analyses and measurements were in good agreement. Therefore, the operating principle was confirmed. The results of the transport experiment showed that the average speed of the 8.5-g slider was 7.9 mm/s.

Investigation on substrate specificity and catalytic activity of serine protease neuropsin.

Neuropsin is one of serine proteases mainly found at the hippocampus and the amygdala, where it contributes to the long-term potentiation and memory acquisition by rebuilding of synaptic connections. Despite of the importance of neuropsin, the substrate specificity and regulation mechanisms of neuropsin have been unclear. Thus, we investigated the substrate specificity and the catalytic activity of neuropsin by the protein-ligand docking and molecular dynamics (MD) simulations and succeeded to reproduce the trend of the experimental results. Our study revealed that the substrate specificity and the activity of neuropsin depended on multiple factors: the substrate charge, the substrate orientation, the hydrogen bond network within the catalytic triad and the substrate, and the formation of the oxyanion hole. The apo neuropsin was not reactive without proper alignment of catalytic triad. The substrate binding induced the reactive alignment of catalytic triad. Then the substrate-neuropsin interaction forms the oxyanion hole that stabilizes the transition state and reduces the free-energy barrier of the following scission reaction.

Regularity of colour statistics in explaining colour composition preferences in art paintings.

This study explores the role of colour statistics in painting preferences and tests the 'matching-to-nature' hypothesis which posits that the preference for the colour composition of paintings depends on the extent to which the paintings resemble the colour statistics of natural scenes. A preference judgement experiment was conducted with 31,353 participants using original and hue-rotated versions of 1,200 paintings. Multiple regression analyses were performed between the measured preferences and paintings' colour statistics to reveal which colour statistics explained the preference data and to what extent. The colour statistics of art paintings that explained the preference data were compared to the colour statistics of natural scenes. The results identified the colour statistics that significantly contributed to explaining painting preferences, and the distributions of the paintings' colour statistics systematically differed from those of natural scenes. These findings suggest that the human visual system encodes colour statistics to make aesthetic judgements based on the artistic merit of colour compositions, and not on their similarity to natural scenes.

Distinguishing mirror from glass: A "big data" approach to material perception.

Distinguishing mirror from glass is a challenging visual inference, because both materials derive their appearance from their surroundings, yet we rarely experience difficulties in telling them apart. Very few studies have investigated how the visual system distinguishes reflections from refractions and to date, there is no image-computable model that emulates human judgments. Here we sought to develop a deep neural network that reproduces the patterns of visual judgments human observers make. To do this, we trained thousands of convolutional neural networks on more than 750,000 simulated mirror and glass objects, and compared their performance with human judgments, as well as alternative classifiers based on "hand-engineered" image features. For randomly chosen images, all classifiers and humans performed with high accuracy, and therefore correlated highly with one another. However, to assess how similar models are to humans, it is not sufficient to compare accuracy or correlation on random images. A good model should also predict the characteristic errors that humans make. We, therefore, painstakingly assembled a diagnostic image set for which humans make systematic errors, allowing us to isolate signatures of human-like performance. A large-scale, systematic search through feedforward neural architectures revealed that relatively shallow (three-layer) networks predicted human judgments better than any other models we tested. This is the first image-computable model that emulates human errors and succeeds in distinguishing mirror from glass, and hints that mid-level visual processing might be particularly important for the task.

Universality and superiority in preference for chromatic composition of art paintings.

Color composition in paintings is a critical factor affecting observers' aesthetic judgments. We examined observers' preferences for the color composition of Japanese and Occidental paintings when their color gamut was rotated. In the experiment, observers were asked to select their preferred image from original and three hue-rotated images in a four-alternative forced choice paradigm. Despite observers' being unfamiliar with the presented artwork, the original paintings (0 degrees) were preferred more frequently than the hue-rotated ones. Furthermore, the original paintings' superiority was observed when the images were divided into small square pieces and their positions randomized (Scrambled condition), and when the images were composed of square pieces collected from different art paintings and composed as patchwork images (Patchwork condition). Therefore, the original paintings' superiority regarding preference was quite robust, and the specific objects in the paintings associated with a particular color played only a limited role. Rather, the original paintings' general trend in color statistics influenced hue-angle preference. Art paintings likely share common statistical regulations in color distributions, which may be the basis for the universality and superiority of the preference for original paintings.

Tumor suppression and improvement in immune systems by specific activation of dopamine D1-receptor-expressing neurons in the nucleus accumbens.

Recent research has suggested that the mesolimbic dopamine network that mainly terminates in the nucleus accumbens may positively control the peripheral immune system. The activation of dopamine receptors in neurons in the nucleus accumbens by the release of endogenous dopamine is thus expected to contribute to efferent immune regulation. As in the stimulation of Gs-coupled dopamine D1-receptors or Gi-coupled D2-receptors by endogenous dopamine, we investigated whether specific stimulation of dopamine D1-receptor-expressing neurons or inhibition of dopamine D2-receptor-expressing neurons in the nucleus accumbens could produce anti-tumor effects and improve the immune system in transgenic mice using pharmacogenetic techniques. Repeated stimulation of D1-receptor-expressing neurons in either the medial shell, lateral shell or core regions of the nucleus accumbens significantly decreased tumor volume under a state of tumor transplantation, whereas repeated suppression of D2-receptor-expressing neurons in these areas had no effect on this event. The number of splenic CD8+ T cells was significantly increased following repeated stimulation of D1-receptor-expressing neurons in the nucleus accumbens of mice with tumor transplantation. Furthermore, this stimulation produced a significant reduction in the population of splenic CD8+ T cells that expressed immune checkpoint-related inhibitory receptors, PD-1, TIM-3 and LAG-3. These findings suggest that repeated stimulation of D1-receptor-expressing neurons (probably D1-receptor-expressing medium spiny neurons) in the nucleus accumbens suppressed tumor progression and improved the immune system by suppressing the exhaustion of splenic CD8+ T cells.

Relief of neuropathic pain by cell-specific manipulation of nucleus accumbens dopamine D1- and D2-receptor-expressing neurons.

Emerging evidence suggests that the mesolimbic dopaminergic network plays a role in the modulation of pain. As chronic pain conditions are associated with hypodopaminergic tone in the nucleus accumbens (NAc), we evaluated the effects of increasing signaling at dopamine D1/D2-expressing neurons in the NAc neurons in a model of neuropathic pain induced by partial ligation of sciatic nerve. Bilateral microinjection of either the selective D1-receptor (Gs-coupled) agonist Chloro-APB or the selective D2-receptor (Gi-coupled) agonist quinpirole into the NAc partially reversed nerve injury-induced thermal allodynia. Either optical stimulation of D1-receptor-expressing neurons or optical suppression of D2-receptor-expressing neurons in both the inner and outer substructures of the NAc also transiently, but significantly, restored nerve injury-induced allodynia. Under neuropathic pain-like condition, specific facilitation of terminals of D1-receptor-expressing NAc neurons projecting to the VTA revealed a feedforward-like antinociceptive circuit. Additionally, functional suppression of cholinergic interneurons that negatively and positively control the activity of D1- and D2-receptor-expressing neurons, respectively, also transiently elicited anti-allodynic effects in nerve injured animals. These findings suggest that comprehensive activation of D1-receptor-expressing neurons and integrated suppression of D2-receptor-expressing neurons in the NAc may lead to a significant relief of neuropathic pain.

Gloss perception: Searching for a deep neural network that behaves like humans.

The visual computations underlying human gloss perception remain poorly understood, and to date there is no image-computable model that reproduces human gloss judgments independent of shape and viewing conditions. Such a model could provide a powerful platform for testing hypotheses about the detailed workings of surface perception. Here, we made use of recent developments in artificial neural networks to test how well we could recreate human responses in a high-gloss versus low-gloss discrimination task. We rendered >70,000 scenes depicting familiar objects made of either mirror-like or near-matte textured materials. We trained numerous classifiers to distinguish the two materials in our images-ranging from linear classifiers using simple pixel statistics to convolutional neural networks (CNNs) with up to 12 layers-and compared their classifications with human judgments. To determine which classifiers made the same kinds of errors as humans, we painstakingly identified a set of 60 images in which human judgments are consistently decoupled from ground truth. We then conducted a Bayesian hyperparameter search to identify which out of several thousand CNNs most resembled humans. We found that, although architecture has only a relatively weak effect, high correlations with humans are somewhat more typical in networks of shallower to intermediate depths (three to five layers). We also trained deep convolutional generative adversarial networks (DCGANs) of different depths to recreate images based on our high- and low-gloss database. Responses from human observers show that two layers in a DCGAN can recreate gloss recognizably for human observers. Together, our results indicate that human gloss classification can best be explained by computations resembling early to mid-level vision.

Development of a new in vitro assay system for evaluating the effects of chemicals on DNA methylation.

Epigenetic toxicity, a phenomenon in which chemicals exert epigenetic effects and produce toxicity, has been attracting attention in recent years due to advances in toxicology accompanying the development of life sciences. However, it has been difficult to identify epigenetic toxicants due to the lack of a simple experimental system to evaluate epigenetic toxicity. In this study, we developed a prototype of an in vitro reporter assay system for assessing the effects of chemicals on DNA methylation using two promoters showing different degrees of DNA methylation, Agouti IAP and Daz1 promoters, and a luciferase reporter. The system successfully detected DNA demethylating activity using 5-azacytidine, a chemical having DNA demethylation activity, as a positive control chemical, and demethylation of cytosine of CpG in the promoter was confirmed by pyrosequencing analysis. Next, in order to improve the detection sensitivity of the DNA demethylating activity of this system, we tried to increase the basal level of methylation of the Daz1 promoter by pre-methylase treatment of the reporter vectors. As a result, the detection sensitivity of the system was successfully improved in cells where the basal level of methylation was indeed increased by methylase treatment. Thus, the developed assay system here is effective for the simple evaluation of chemicals that affect DNA methylation.

Early Improvement of Non-islet Cell Tumor Hypoglycemia by Chemotherapy Using Lenvatinib in a Case with Type 2 Diabetes and Hepatocellular Carcinoma Producing Big IGF-II.

A 77-year-old man was treated with a DPP-4 inhibitor for type 2 diabetes. Hypoglycemia occurred frequently, and an examination revealed a tumor with a maximum diameter of 140 mm in both lobes of the liver. Western immunoblotting detected a high-molecular-weight form of insulin-like growth factor-II, and non-islet cell tumor hypoglycemia was diagnosed. Although prednisolone 40 mg was started, hypoglycemia continued to occur frequently. Surgical tumor removal was not indicated, so lenvatinib was initiated. Hypoglycemia improved quickly, and the tumor shrank until it had partially disappeared. His condition continued to improve, and he was discharged.

Cell-specific overexpression of COMT in dopaminergic neurons of Parkinson's disease.

The mechanism by which dopaminergic neurons are selectively affected in Parkinson's disease is not fully understood. In this study, we found a dramatic increase in the expression of catechol-O-methyltransferase (COMT), along with a lower level of DNA methylation, in induced pluripotent stem cell-derived dopaminergic neurons from patients with parkin (PARK2) gene mutations compared to those from healthy controls. In addition, a significant increase in the expression of COMT was found in dopaminergic neurons of isogenic PARK2 induced pluripotent stem cell lines that mimicked loss of function of PARK2 by CRISPR Cas9 technology. In dopamine transporter (DAT)-Cre mice, overexpression of COMT, specifically in dopaminergic neurons of the substantia nigra, produced cataleptic behaviours associated with impaired motor coordination. These findings suggest that upregulation of COMT, likely resulting from DNA hypomethylation, in dopaminergic neurons may contribute to the initial stage of neuronal dysfunction in Parkinson's disease.

Regional and temporal regulation and role of somatostatin receptor subtypes in the mouse brain following systemic kainate-induced acute seizures.

Somatostatin reduces neuronal excitability via somatostatin receptors (Sst1-Sst5) and inhibits seizure activity. However, the expression status of the Sst subtypes in epileptic mice and their role in the antiepileptic effects of somatostatin remain unclear. Here, we show that the Sst subtypes are regulated differently by epileptic neuronal activity in mice. Systemic kainate injection rapidly and transiently elevated the Sst2 and Sst3 mRNA and reduced Sst1 and Sst4 mRNA in the hippocampus; however, among all the subtypes, only Sst2 mRNA was increased in the excitatory neurons of the basolateral amygdala, accompanied by a decrease in the level of Sst2 protein. Following kainate administration, recovery from seizure was delayed by reduced expression of Sst2 in the basolateral amygdala, but not in the dentate gyrus of the hippocampus; higher expression levels of Bdnf, a neuronal activity marker, were observed in both conditions. These results suggest that Sst2 contributes to seizure termination by feedback inhibition in the amygdala. This could be a potential therapeutic target for acute seizures.

Dynamic Visual Cues for Differentiating Mirror and Glass.

Mirror materials (perfect specular surfaces such as polished metal) and glass materials (transparent and refraction media) are quite commonly encountered in everyday life. The human visual system can discriminate these complex distorted images formed by reflection or transmission of the surrounding environment even though they do not intrinsically possess surface colour. In this study, we determined the cues that aid mirror and glass discrimination. From video analysis, we found that glass objects have more opposite motion components relative to the direction of object rotation. Then, we hypothesised a model developed using motion transparency because motion information is not only present on the front side, but also on the rear side of the object surface in the glass material object. In materials judging experiments, we found that human performance with rotating video stimuli is higher than that with static stimuli (simple images). Subsequently, we compared the developed model derived from motion coherency to human rating performance for transparency and specular reflection. The model sufficiently identified the different materials using dynamic information. These results suggest that the visual system relies on dynamic cues that indicate the difference between mirror and glass.

Effect of ghrelin on the motor deficit caused by the ablation of nigrostriatal dopaminergic cells or the inhibition of striatal dopamine receptors.

Ghrelin plays roles in a wide range of central functions by activating the growth hormone secretagogue receptor (GHSR). This receptor has recently been found in the substantia nigra (SN) to control dopamine (DA)-related physiological functions. The dysregulation of DA neurons in the SN pars compacta (SNc) and the consequent depletion of striatal DA are known to underlie the motor deficits observed in Parkinson's disease (PD). In the present study, we further investigated the role of the SN-ghrelin system in motor function under the stereotaxic injection of AAV-CMV-FLEX-diphtheria toxin A (DTA) into the SN of dopamine transporter (DAT)-Cre (DATSN::DTA) mice to expunge DA neurons of the SNc. First, we confirmed the dominant expression of GHSR1a, which is a functional GHSR, in tyrosine hydroxylase (TH)-positive DA neurons in the SNc of control mice. In DATSN::DTA mice, we clearly observed motor dysfunction using several behavioral tests. An immunohistochemical study revealed a dramatic loss of TH-positive DA neurons in the SNc and DAT-labeled axon terminals in the striatum, and an absence of mRNAs for TH and DAT in the SN of DATSN::DTA mice. The mRNA level of GHSR1a was drastically decreased in the SN of these mice. In normal mice, we also found the mRNA expression of GHSR1a within GABAergic neurons in the SN pars reticulata (SNr). Under these conditions, a single injection of ghrelin into the SN failed to improve the motor deficits caused by ablation of the nigrostriatal DA network using DATSN::DTA mice, whereas intra-SN injection of ghrelin suppressed the motor dysfunction caused by the administration of haloperidol, which is associated with the transient inhibition of DA transmission. These findings suggest that phasic activation of the SNc-ghrelin system could improve the dysregulation of nigrostriatal DA transmission related to the initial stage of PD, but not the motor deficits under the depletion of nigrostriatal DA. Although GHSRs are found in non-DA cells of the SNr, GHSRs on DA neurons in the SNc may play a crucial role in motor function.