Ultrasonic vocalization (USVs) is a promising tool to measure behavioral anxiety in rodents as USV recording is noninvasive, behaviorally relevant, ethological, and reproducible. Studies reporting ...the effects of stress-induced USVs in adult mice remain limited and debated. We investigated the conditions under which mice emit aversive USVs and evaluated the effects of psychiatric drugs on stress-induced USVs. Male C57BL/6J mice were used. USVs during entire stress sessions were recorded according to their frequency. To investigate the effect of psychiatric drugs on USVs, the number of USVs under cold-restraint stress conditions before and after drug administration was compared. Immediately after stress exposure, blood samples were collected and plasma corticosterone levels were measured. The combination of cold and restraint stress conditions significantly increased the USV numbers and plasma corticosterone levels compared with each stress alone. A benzodiazepine anxiolytic (midazolam) and δ-opioid receptor agonist putative anxiolytic (KNT-127) significantly reduced the stress-induced USV number and plasma corticosterone levels; however, a monoaminergic antidepressant (duloxetine) and N-methyl-D-aspartic acid receptor antagonist antidepressant (ketamine) did not reduce the USV numbers. No changes were noted in the USV numbers after repeated exposure to cold-restraint stress on days 1 and 3. The suppressive effect of midazolam on day 3 was comparable to that on day 1. Stress-induced USV may be used as a quantitative measure of anxiety to systematically assess the effects of anxiolytics. Therefore, cold-restraint stress-induced USVs may be used as a novel tool to measure rodent anxiety and as a useful anxiolytic-screening system.
Increasing evidence has demonstrated that emotional states and intestinal conditions are inter-connected in so-called “brain–gut interactions.” Indeed, many psychiatric disorders are accompanied by ...gastrointestinal symptoms, such as the irritable bowel syndrome (IBS). However, the functional connection remains elusive, partly because there are few useful experimental animal models. Here, we focused on a highly validated animal model of stress-induced psychiatric disorders, such as depression, known as the chronic vicarious social defeat stress (cVSDS) model mice, which we prepared using exposure to repeated psychological stress, thereafter examining their intestinal conditions. In the charcoal meal test and the capsaicin-induced hyperalgesia test, cVSDS model mice showed a significantly higher intestinal transit ratio and increased visceral pain-related behaviors, respectively. These changes persisted over one month after the stress session. On the other hand, the pathological evaluations of the histological and inflammatory scores of naive and cVSDS model mice did not differ. Furthermore, keishikashakuyakuto—a kampo medicine clinically used for the treatment of IBS—normalized the intestinal motility change in cVSDS model mice. Our results indicate that cVSDS model mice present IBS-like symptoms such as chronic intestinal peristaltic changes and abdominal hyperalgesia without organic lesion. We therefore propose the cVSDS paradigm as a novel animal model of IBS with wide validity, elucidating the correlation between depressive states and intestinal abnormalities.
Disulfiram is an FDA approved drug for the treatment of alcoholism. The drug acts by inhibiting aldehyde dehydrogenase, an enzyme essential to alcohol metabolism. However, a recent study has ...demonstrated that disulfiram also potently inhibits the cytoplasmic protein FROUNT, a common regulator of chemokine receptor CCR2 and CCR5 signaling. Several studies have reported that chemokine receptors are associated with the regulation of emotional behaviors in rodents, such as anxiety. Therefore, this study was performed to clarify the effect of disulfiram on emotional behavior in rodents. The anxiolytic-like effects of disulfiram were investigated using an elevated plus-maze (EPM) test, a typical screening model for anxiolytics. Disulfiram (40 or 80 mg/kg) significantly increased the amount of time spent in the open arms of the maze and the number of open arm entries without affecting the total open arms entries. Similar results were obtained in mice treated with a selective FROUNT inhibitor, disulfiram-41 (10 mg/kg). These disulfiram-associated behavioral changes were similar to those observed following treatment with the benzodiazepine anxiolytic diazepam (1.5 mg/kg). Moreover, disulfiram (40 mg/kg) significantly and completely attenuated increased extracellular glutamate levels in the prelimbic-prefrontal cortex (PL-PFC) during stress exposure on the elevated open-platform. However, no effect in the EPM test was seen following administration of the selective aldehyde dehydrogenase inhibitor cyanamide (40 mg/kg). In contrast to diazepam, disulfiram caused no sedation effects in the open-field, coordination disorder on a rotarod, or amnesia in a Y-maze. This is the first report suggesting that disulfiram produces anxiolytic-like effects in rodents. We found that the presynaptic inhibitory effects on glutaminergic neurons in the PL-PFC may be involved in its underlying mechanism. Disulfiram could therefore be an effective and novel anxiolytic drug that does not produce benzodiazepine-related adverse effects, such as amnesia, coordination disorder, or sedation, as found with diazepam. We propose that the inhibitory activity of disulfiram against FROUNT function provides an effective therapeutic option in anxiety.
Scene Graphs are widely applied in computer vision as a graphical representation of relationships between objects shown in images. However, these applications have not yet reached a practical stage ...of development owing to biased training caused by long-tailed predicate distributions. In recent years, many studies have tackled this problem. In contrast, relatively few works have considered predicate similarities as a unique dataset feature which also leads to the biased prediction. Due to the feature, infrequent predicates (e.g., " parked on ", " covered in ") are easily misclassified as closely-related frequent predicates (e.g., " on ", " in "). Utilizing predicate similarities, we propose a new classification scheme that branches the process to several fine-grained classifiers for similar predicate groups. The classifiers aim to capture the differences among similar predicates in detail. We also introduce the idea of transfer learning to enhance the features for the predicates which lack sufficient training samples to learn the descriptive representations. Our target here is to improve the average precision scores even for the instances with the tail predicators. The results of extensive experiments on the Visual Genome dataset show that the combination of our method and an existing debiasing approach greatly improves performance on tail predicates in challenging SGCls/SGDet tasks. Nonetheless, the overall performance of the proposed approach does not reach that of the current state of the art, so further analysis remains necessary as future work.
Ultrasonic vocalization (USVs) is a promising tool to measure behavioral anxiety in rodents as USV recording is noninvasive, behaviorally relevant, ethological, and reproducible. Studies reporting ...the effects of stress-induced USVs in adult mice remain limited and debated. We investigated the conditions under which mice emit aversive USVs and evaluated the effects of psychiatric drugs on stress-induced USVs. Male C57BL/6J mice were used. USVs during entire stress sessions were recorded according to their frequency. To investigate the effect of psychiatric drugs on USVs, the number of USVs under cold-restraint stress conditions before and after drug administration was compared. Immediately after stress exposure, blood samples were collected and plasma corticosterone levels were measured. The combination of cold and restraint stress conditions significantly increased the USV numbers and plasma corticosterone levels compared with each stress alone. A benzodiazepine anxiolytic (midazolam) and δ-opioid receptor agonist putative anxiolytic (KNT-127) significantly reduced the stress-induced USV number and plasma corticosterone levels; however, a monoaminergic antidepressant (duloxetine) and N-methyl-D-aspartic acid receptor antagonist antidepressant (ketamine) did not reduce the USV numbers. No changes were noted in the USV numbers after repeated exposure to cold-restraint stress on days 1 and 3. The suppressive effect of midazolam on day 3 was comparable to that on day 1. Stress-induced USV may be used as a quantitative measure of anxiety to systematically assess the effects of anxiolytics. Therefore, cold-restraint stress–induced USVs may be used as a novel tool to measure rodent anxiety and as a useful anxiolytic-screening system.
Scene Graphs are widely applied in computer vision as a graphical representation of relationships between objects shown in images. However, these applications have not yet reached a practical stage ...of development owing to biased training caused by long-tailed predicate distributions. In recent years, many studies have tackled this problem. In contrast, relatively few works have considered predicate similarities as a unique dataset feature which also leads to the biased prediction. Due to the feature, infrequent predicates (e.g., parked on, covered in) are easily misclassified as closely-related frequent predicates (e.g., on, in). Utilizing predicate similarities, we propose a new classification scheme that branches the process to several fine-grained classifiers for similar predicate groups. The classifiers aim to capture the differences among similar predicates in detail. We also introduce the idea of transfer learning to enhance the features for the predicates which lack sufficient training samples to learn the descriptive representations. The results of extensive experiments on the Visual Genome dataset show that the combination of our method and an existing debiasing approach greatly improves performance on tail predicates in challenging SGCls/SGDet tasks. Nonetheless, the overall performance of the proposed approach does not reach that of the current state of the art, so further analysis remains necessary as future work.
In the development of science, accurate and reproducible documentation of the experimental process is crucial. Automatic recognition of the actions in experiments from videos would help experimenters ...by complementing the recording of experiments. Towards this goal, we propose FineBio, a new fine-grained video dataset of people performing biological experiments. The dataset consists of multi-view videos of 32 participants performing mock biological experiments with a total duration of 14.5 hours. One experiment forms a hierarchical structure, where a protocol consists of several steps, each further decomposed into a set of atomic operations. The uniqueness of biological experiments is that while they require strict adherence to steps described in each protocol, there is freedom in the order of atomic operations. We provide hierarchical annotation on protocols, steps, atomic operations, object locations, and their manipulation states, providing new challenges for structured activity understanding and hand-object interaction recognition. To find out challenges on activity understanding in biological experiments, we introduce baseline models and results on four different tasks, including (i) step segmentation, (ii) atomic operation detection (iii) object detection, and (iv) manipulated/affected object detection. Dataset and code are available from https://github.com/aistairc/FineBio.
Mycophenolic acid as a latent agonist of PPARγ Ubukata, Makoto; Takamori, Hitomi; Ohashi, Misaki ...
Bioorganic & medicinal chemistry letters,
09/2007, Volume:
17, Issue:
17
Journal Article
Peer reviewed
Mycophenolic acid (
1), known as an inhibitor of inosine monophosphate dehydrogenase (IMPDH), was found to inhibit the differentiation of 3T3-L1 pre-adipocytes into mature adipocytes. Although the ...effect of
1 could be attributed to inhibition of IMPDH, we identified
1 as a latent agonist of PPARγ. This is the first report that molecular target of
1 except IMPDH was found.
Mycophenolic acid (MPA), known as an inhibitor of inosine monophosphate dehydrogenase (IMPDH), was found to inhibit the differentiation of 3T3-L1 pre-adipocytes into mature adipocytes. Although the effect of MPA was attributed to inhibition of IMPDH, we uncovered a hidden biological property of MPA as an agonist of peroxisome proliferator activated receptor γ (PPARγ).
This study aims to clarify the feature of Ginkgo trees landscape spread all over old Yamazaki village, Inazawa city, Aichi as cultural landscape through analysis of the process of planting ginkgo ...trees from relationship with village structure and planting design in outside spaces . Through field surveys and mapping analysis by using aerial photographs and historical documents, the process to plant ginkgo trees can be divided to four stages as result. The places of ginkgo plantation has been shifted from surroundings of houses to the whole of the village, affected by economical reasons. Present ginkgo landscape around this area was generated from 1980’s to 2000’s, when 70% of present ginkgo trees were planted, caused by a reduction in rice acreage. The aim of its plantation turned out to have changed by the time. At the beginning, there was no particular aim in planting, except symbol of premises. However, an information that ginkgo trees could be traded at high value brought about the intentional cultivation of ginkgo trees. Ginkgo plantation have come to be controlled more definitely. The control of the heights of the gingko trees can brings the characteristic landscape in Yamazaki, where people enjoy yellow leaves near tree canopies.
Mycophenolic acid as a latent agonist of PPARgamma Ubukata, Makoto; Takamori, Hitomi; Ohashi, Misaki ...
Bioorganic & medicinal chemistry letters,
2007-Sep-01, 20070901, Volume:
17, Issue:
17
Journal Article
Peer reviewed
Mycophenolic acid (MPA), known as an inhibitor of inosine monophosphate dehydrogenase (IMPDH), was found to inhibit the differentiation of 3T3-L1 pre-adipocytes into mature adipocytes. Although the ...effect of MPA was attributed to inhibition of IMPDH, we uncovered a hidden biological property of MPA as an agonist of peroxisome proliferator activated receptor gamma (PPARgamma).
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