Illusory upward self-motion results in a decrease in perceived room temperature

Purpose: Stationary observers often experience illusory self-motion (vection) when they are exposed to large patterns of optic flow. The effect of different temperatures on the strength of vection was investigated. Method: Eleven participants were exposed to visual stimuli that induced illusory motion (up, down) in three room temperatures (26°C - 27°C, 21°C - 22°C, 5°C - 6°C). Participants rated (a) the vection magnitude, and (b) the room temperature (twice; before and after vection). Results: Upward vection was rated as stronger than downward vection in the 26°C - 27°C temperature. In addition, after experiencing upward and downward vection, subjective ratings of room temperature decreased and increased, respectively, when the room temperature was 26°C - 27°C. This effect was not observed when the room was 5°C - 6°C. Conclusion: These results suggest that a cross modal association exists between the direction “up” and 26°C - 27°C temperatures

Vection induced by low-level motion extracted from complex animation films

This study examined the contributions of low-, mid- and high-level visual motion information to vection. We compared the vection experiences induced by hand-drawn and computer-generated animation clips to those induced by versions of these movies that contained only their pure optic flow. While the original movies were found to induce longer and stronger vection experiences than the pure optic flow, vection onsets were not significantly altered by removing the mid- and high-level information. We conclude that low-level visual motion information appears to be important for vection induction, whereas mid- and higher-level display information appears to be important for sustaining and strengthening this vection after its initial induction

ELF3 suppresses gallbladder cancer development through downregulation of the EREG/EGFR/mTOR complex 1 signalling pathway

The prognosis of gallbladder cancer (GBC) remains poor, and a better understanding of GBC molecular mechanisms is important. Genome sequencing of human GBC has demonstrated that loss-of-function mutations of E74-like ETS transcription factor 3 (ELF3) are frequently observed, with ELF3 considered to be a tumour suppressor in GBC. To clarify the underlying molecular mechanisms by which ELF3 suppresses GBC development, we performed in vivo analysis using a combination of autochthonous and allograft mouse models. We first evaluated the clinical significance of ELF3 expression in human GBC tissues and found that low ELF3 expression was associated with advanced clinical stage and deep tumour invasion. For in vivo analysis, we generated Pdx1-Cre; KrasG12D; Trp53R172H; Elf3f/f (KPCE) mice and Pdx1-Cre; KrasG12D; Trp53R172H; Elf3wt/wt (KPC) mice as a control and analysed their gallbladders histologically. KPCE mice developed larger papillary lesions in the gallbladder than those developed by KPC mice. Organoids established from the gallbladders of KPCE and KPC mice were analysed in vitro. RNA sequencing showed upregulated expression of epiregulin (Ereg) in KPCE organoids, and western blotting revealed that EGFR/mechanical targets of rapamycin complex 1 (mTORC1) were upregulated in KPCE organoids. In addition, ChIP assays on Elf3-overexpressing KPCE organoids showed that ELF3 directly regulated Ereg. Ereg deletion in KPCE organoids (using CRISPR/Cas9) induced EGFR/mTORC1 downregulation, indicating that ELF3 controlled EGFR/mTORC1 activity through regulation of Ereg expression. We also generated allograft mouse models using KPCE and KPC organoids and found that KPCE organoid allograft tumours exhibited poorly differentiated structures with mTORC1 upregulation and mesenchymal phenotype, which were suppressed by Ereg deletion. Furthermore, EGFR/mTORC1 inhibition suppressed cell proliferation and epithelial–mesenchymal transition in KPCE organoids. Our results suggest that ELF3 suppresses GBC development via downregulation of EREG/EGFR/mTORC1 signalling. EGFR/mTORC1 inhibition is a potential therapeutic option for GBC with ELF3 mutation. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

Context-Dependent Roles of Hes1 in the Adult Pancreas and Pancreatic Tumor Formation

[Background & Aims] The Notch signaling pathway is an important pathway in the adult pancreas and in pancreatic ductal adenocarcinoma (PDAC), with hairy and enhancer of split-1 (HES1) as the core molecule in this pathway. However, the roles of HES1 in the adult pancreas and PDAC formation remain controversial. [Methods] We used genetically engineered dual-recombinase mouse models for inducing Hes1 deletion under various conditions. [Results] The loss of Hes1 expression in the adult pancreas did not induce phenotypic alterations. However, regeneration was impaired after caerulein-induced acute pancreatitis. In a pancreatic intraepithelial neoplasia (PanIN) mouse model, PanINs rarely formed when Hes1 deletion preceded PanIN formation, whereas more PanINs were formed when Hes1 deletion succeeded PanIN formation. In a PDAC mouse model, PDAC formation was also enhanced by Hes1 deletion after PanIN/PDAC development; therefore, Hes1 promotes PanIN initiation but inhibits PanIN/PDAC progression. RNA sequencing and chromatin immunoprecipitation-quantitative polymerase chain reaction revealed that Hes1 deletion enhanced epithelial-to-mesenchymal transition via Muc5ac up-regulation in PDAC progression. The results indicated that HES1 is not required for maintaining the adult pancreas under normal conditions, but is important for regeneration during recovery from pancreatitis; moreover, Hes1 plays different roles, depending on the tumor condition. [Conclusions] Our findings highlight the context-dependent roles of HES1 in the adult pancreas and pancreatic cancer

Anti-integrin αvβ6 autoantibodies in patients with primary sclerosing cholangitis

[Background] Patients with primary sclerosing cholangitis (PSC) possess autoantibodies against biliary epithelial cells. However, the target molecules remain unknown. [Methods] The sera of patients with PSC and controls were subjected to enzyme-linked immunosorbent assays to detect autoantibodies using recombinant integrin proteins. Integrin αvβ6 expression in the bile duct tissues was examined using immunofluorescence. The blocking activity of the autoantibodies was examined using solid-phase binding assays. [Results] Anti-integrin αvβ6 antibodies were detected in 49/55 (89.1%) patients with PSC and 5/150 (3.3%) controls (P < 0.001), with a sensitivity and specificity of 89.1% and 96.7%, respectively, for PSC diagnosis. When focusing on the presence or absence of IBD, the proportion of the positive antibodies in PSC with IBD was 97.2% (35/36) and that in PSC alone was 73.7% (14/19) (P = 0.008). Integrin αvβ6 was expressed in bile duct epithelial cells. Immunoglobulin (Ig)G from 15/33 patients with PSC blocked integrin αvβ6-fibronectin binding through an RGD (Arg–Gly–Asp) tripeptide motif. [Conclusions] Autoantibodies against integrin αvβ6 were detected in most patients with PSC; anti-integrin αvβ6 antibody may serve as a potential diagnostic biomarker for PSC

Identification of an Anti–Integrin αvβ6 Autoantibody in Patients With Ulcerative Colitis

指定難病「潰瘍性大腸炎」の自己抗体発見 --新たな診断や治療開発へ--. 京都大学プレスリリース. 2021-03-09.Background and Aims: Ulcerative colitis is the most frequent type of inflammatory bowel disease and is characterized by colonic epithelial cell damage. Although involvement of autoimmunity has been suggested in ulcerative colitis, specific autoantigens/antibodies have yet to be elucidated. Methods: Using 23 recombinant integrin proteins, we performed enzyme-linked immunosorbent assays on sera from patients with ulcerative colitis and controls. Integrin expression and IgG binding in the colon tissues of patients with ulcerative colitis and controls were examined using immunofluorescence and coimmunoprecipitation, respectively. The blocking activity of autoantibodies was examined using solid-phase binding and cell adhesion assays. Results: Screening revealed that patients with ulcerative colitis had IgG antibodies against integrin αvβ6. In the training and validation groups, 103 of 112 (92.0%) patients with ulcerative colitis and only 8 of 155 (5.2%) controls had anti–integrin αvβ6 antibodies (P < .001), resulting in a sensitivity of 92.0% and a specificity of 94.8% for diagnosing ulcerative colitis. Anti–integrin αvβ6 antibody titers coincided with ulcerative colitis disease activity, and IgG1 was the major subclass. Patient IgG bound to the integrin αvβ6 expressed on colonic epithelial cells. Moreover, IgG of patients with ulcerative colitis blocked integrin αvβ6–fibronectin binding through an RGD (Arg-Gly-Asp) tripeptide motif and inhibited cell adhesion. Conclusions: A significant majority of patients with ulcerative colitis had autoantibodies against integrin αvβ6, which may serve as a potential diagnostic biomarker with high sensitivity and specificity

Vection induced by illusory motion in a stationary image

Ilusory self-motion (vection) can be induced by large areas of visual motion stimulation. Here we demonstrate for the first time that illusory expansion can induce vection in the absence of any physical display motion

Virtual swimming - breaststroke body movements facilitate vection

Visually induced illusory self-motion (vection) was facilitated by active breaststroke arm and body movements. Optic flow was generated by having the standing observer make these arm movements, which were detected by Kinect and incorporated into the display. When generated, this optic flow was either expanding (i.e. congruent with the observer\u27s head motion) or contracting (i.e. incongruent with his/her head motion). Optic flow generated during these active movement conditions was also later played back to the observer during passive viewing conditions. On each of these trials, we recorded vection strength (latency, duration and magnitude). We found that: (i) both congruent and incongruent breaststroke movements increased vection (i.e. compared to passive viewing conditions); and (ii) congruent breaststroke movements increased vection more than incongruent ones. We name the enhancement provided by this type of active movement \u27virtual swimming\u27. This demonstration shows that even unusual body movements can function as a self-motion signal

Walking without visual motion reduces subsequent vection

Paper presented at the Australasian Experimental Psychology Conference 2015, 8-11 April 2015, Sydney, Australia

Hunger enhances vertical vection

Hunger was found to facilitate visually induced illusory upward and downward self-motions (vertical vection), but not illusory self-motion in depth (vection in depth). We propose that the origin of this hunger effect lies in the possibility that vertical self-motions (both real and illusory) are more likely to induce changes in visceral state