Immunohistochemical Examination of a Resected Advanced Hilar Cholangiocarcinoma Arising in a 29-Year-Old Male without Primary Sclerosing Cholangitis

A 29-year-old man with advanced hilar cholangiocarcinoma was successfully treated with an extended right lobectomy. The carbohydrate antigen 19-9 (CA19-9) level was elevated to 939 IU/l, and the pathological findings revealed moderately differentiated tubular adenocarcinoma which involved almost the entire thickness of the hepatic duct and the adjacent liver tissue (T3) and which was associated with lymph node metastasis (N1). It was a stage IIB (T3N1M0) tubular adenocarcinoma according to UICC pathological staging. Immunohistochemical examination revealed that Ki-67, cyclin D1, and MMP-7 were positive, and 14-3-3σ and p27 were negative. The pathological and immunohistochemical findings indicated high malignant potential indicating poor prognosis. We administrated the postoperative adjunct gemcitabine combined with S-1 chemotherapy. The patient is alive without recurrence and doing well two years after surgery. We also review other reports of cholangiocarcinoma patients aged less than 30 years

Long‐term monitoring of huddling behavior in mice using online image processing

Abstract Many animal species, including mice, form societies of numerous individuals for survival. Understanding the interactions between individual animals is crucial for elucidating group behavior. One such behavior in mice is huddling, yet its analysis has been limited. In this study, we propose a cost‐effective method for monitoring long‐term huddling behavior in mice using online image processing with OpenCV. This method treats a single mouse or a group of mice as a cluster of pixels (a ‘blob’) in video images, extracting and saving only essential information such as areas, coordinates, and orientations. This approach reduces data storage needs to 1/200000th of what would be required if the video were recorded in its compressed form, thereby enabling long‐term behavioral analysis. To validate the performance of our algorithm, ~2000 video frames were randomly chosen. We manually counted the number of clusters of mice in these frames and compared them with the number of blobs automatically detected by the algorithm. The results indicated a high level of consistency, exceeding 90% across the selected video frames. Initial observations of both male and female groups suggested some variations in huddling behavior among male and female groups; however, these results should be interpreted cautiously due to a small sample. Group behavior is known to be disrupted in several neuropsychiatric disorders, such as autism. Various mouse models of these disorders have been proposed. Our measurement system, when combined with drug or genetic modification screening, could provide a valuable tool for high‐throughput analyses of huddling behavior

Influences of rewarding and aversive outcomes on activity in macaque lateral prefrontal cortex

Both appetitive and aversive outcomes can reinforce animal behavior. It is not clear, however, whether the opposing kinds of reinforcers are processed by specific or common neural mechanisms. To investigate this issue, we studied macaque monkeys that performed a memory-guided saccade task for three different outcomes, namely delivery of liquid reward, avoidance of air puff, and feedback sound only. Animals performed the task best in rewarded trials, intermediately in aversive trials, and worst in sound-only trials. Most task-related activity in lateral prefrontal cortex was differentially influenced by the reinforcers. Aversive avoidance had clear effects on some prefrontal neurons, although the effects of rewards were more common. We also observed neurons modulated by both positive and negative reinforcers, reflecting reinforcement or attentional processes. Our results demonstrate that information about positive and negative reinforcers is processed differentially in prefrontal cortex, which could contribute to the role of this structure in goal-directed behavior

Emotional Contagion From Humans to Dogs Is Facilitated by Duration of Ownership

Emotional contagion is a primitive form of empathy that does not need higher psychological functions. Recent studies reported that emotional contagion exists not only between humans but also among various animal species. The dog (Canis familiaris) is a unique animal and the oldest domesticated species. Dogs have coexisted with humans for more than 30, 000 years and are woven into human society as partners bonding with humans. Dogs have acquired human-like communication skills and, likely as a result of the domestication process, the ability to read human emotions; therefore, it is feasible that there may be emotional contagion between human and dogs. However, the higher time-resolution of measurement of emotional contagion between them is yet to be conducted. We assessed the emotional reactions of dogs and humans by heart rate variability (HRV), which reflects emotion, under a psychological stress condition on the owners. The correlation coefficients of heart beat (R-R) intervals (RRI), the standard deviations of all RR intervals (SDNN), and the square root of the mean of the sum of the square of differences between adjacent RR intervals (RMSSD) between dogs and owners were positively correlated with the duration of dog ownership. Dogs’ sex also influenced the correlation coefficients of the RRI, SDNN, and RMSSD in the control condition; female showed stronger values. These results suggest that emotional contagion from owner to dog can occur especially in females and the time sharing the same environment is the key factor in inducing the efficacy of emotional contagion

Testosterone Increases the Emission of Ultrasonic Vocalizations With Different Acoustic Characteristics in Mice

International audienceTestosterone masculinizes male sexual behavior through an organizational and activational effects. We previously reported that the emission of ultrasonic vocalizations (USVs) in male mice was dependent on the organizational effects of testosterone; females treated with testosterone in the perinatal and peripubertal periods, but not in adults, had increased USV emissions compared to males. Recently, it was revealed that male USVs have various acoustic characteristics and these variations were related to behavioral interactions with other mice. In this regard, the detailed acoustic characteristic changes induced by testosterone have not been fully elucidated. Here, we revealed that testosterone administered to female and male mice modulated the acoustic characteristics of USVs. There was no clear difference in acoustic characteristics between males and females. Call frequencies were higher in testosterone propionate (TP)-treated males and females compared to control males and females. When the calls were classified into nine types, there was also no distinctive difference between males and females, but TP increased the number of calls with a high frequency, and decreased the number of calls with a low frequency and short duration. The transition analysis by call type revealed that even though there was no statistically significant difference, TP-treated males and females had a similar pattern of transition to control males and females, respectively. Collectively, these results suggest that testosterone treatment can enhance the emission of USVs both in male and female, but the acoustic characteristics of TP-treated females were not the same as those of intact males

Coordination of Cellular Dynamics Contributes to Tooth Epithelium Deformations.

The morphologies of ectodermal organs are shaped by appropriate combinations of several deformation modes, such as invagination and anisotropic tissue elongation. However, how multicellular dynamics are coordinated during deformation processes remains to be elucidated. Here, we developed a four-dimensional (4D) analysis system for tracking cell movement and division at a single-cell resolution in developing tooth epithelium. The expression patterns of a Fucci probe clarified the region- and stage-specific cell cycle patterns within the tooth germ, which were in good agreement with the pattern of the volume growth rate estimated from tissue-level deformation analysis. Cellular motility was higher in the regions with higher growth rates, while the mitotic orientation was significantly biased along the direction of tissue elongation in the epithelium. Further, these spatio-temporal patterns of cellular dynamics and tissue-level deformation were highly correlated with that of the activity of cofilin, which is an actin depolymerization factor, suggesting that the coordination of cellular dynamics via actin remodeling plays an important role in tooth epithelial morphogenesis. Our system enhances the understanding of how cellular behaviors are coordinated during ectodermal organogenesis, which cannot be observed from histological analyses

Humanized substitutions of Vmat1 in mice alter amygdala-dependent behaviors associated with the evolution of anxiety

The human vesicular monoamine transporter 1 (VMAT1) harbors unique substitutions (Asn136Thr/Ile) that affect monoamine uptake into synaptic vesicles. These substitutions are absent in all known mammals, suggesting their contributions to distinct aspects of human behavior modulated by monoaminergic transmissions, such as emotion and cognition. To directly test the impact of these human-specific mutations, we introduced the humanized residues into mouse Vmat1 via CRISPR/Cas9-mediated genome editing and examined changes at the behavioral, neurophysiological, and molecular levels. Behavioral tests revealed reduced anxiety-related traits of Vmat1Ile mice, consistent with human studies, and electrophysiological recordings showed altered oscillatory activity in the amygdala under anxiogenic conditions. Transcriptome analyses further identified changes in gene expressions in the amygdala involved in neurodevelopment and emotional regulation, which may corroborate the observed phenotypes. This knock-in mouse model hence provides compelling evidence that the mutations affecting monoaminergic signaling and amygdala circuits have contributed to the evolution of human socio-emotional behaviors

The regulation of the tooth morphogenesis via actin reorganization.

<p><b>(A)</b> The localizations of p-cofilin (green, left upper), cofilin (green, left lower), and F-actin (white, right) were detected by immunohistochemistry. The G0/G1 phase cells (red, center) are visualized with a Fucci probe. The lingual side is on the left in all panels. <b>(B)</b> Estimations of the p-cofilin/cofilin ratios in parts of the tooth germ epithelium (EK, enamel knot; DL, dental lamina; B and L, buccal side and lingual sides of the growing apex of the epithelium). The relative amounts of cofilin and p-cofilin in the regions of the epithelium were determined by immunoblotting (left). The intensities of the bands were calculated and are indicated in the bar graphs (right). <b>(C)</b> Measurements of actin dynamics in the epithelium using fluorescence recovery after photobleaching (FRAP). The right graph illustrates the best-fit curves of the normalized fluorescence intensity during the FRAP assay. The spots indicate the half-recovery times. <b>(D)</b> Gene expression of upstream molecules that regulate cofilin activity in the E14.5 tooth germ. The lingual side is on the left in all panels. The scale bars represent 100 μm. <b>(E)</b> Inhibition of cell proliferation by cofilin phosphorylation in a WST-8 assay. The results are presented as the mean ± s.d. of triplicate experiments. *<i>P</i> < 0.01, analyzed by <i>t</i>-test. LIMK WT, wild-type LIM-kinase (LIMK); LIMK D460A, dominant negative LIMK mutant; Rac V12, dominant active mutant of Rac1. <b>(F)</b> Inhibition of cell migration by cofilin phosphorylation in a wound healing assay. The bars indicate the migration distances of the epithelial cells. The results are presented as the mean ± s.d. of triplicate experiments. *<i>P</i> < 0.01, analyzed by <i>t</i>-test. <b>(G)</b> Schematic summarizing the observed results in this study.</p