Human-Robot Kinaesthetic Interaction Based on Free Energy Principle

The current study investigated possible human-robot kinaesthetic interaction using a variational recurrent neural network model, called PV-RNN, which is based on the free energy principle. Our prior robotic studies using PV-RNN showed that the nature of interactions between top-down expectation and bottom-up inference is strongly affected by a parameter, called the meta-prior, which regulates the complexity term in free energy.The study also compares the counter force generated when trained transitions are induced by a human experimenter and when untrained transitions are induced. Our experimental results indicated that (1) the human experimenter needs more/less force to induce trained transitions when $w$ is set with larger/smaller values, (2) the human experimenter needs more force to act on the robot when he attempts to induce untrained as opposed to trained movement pattern transitions. Our analysis of time development of essential variables and values in PV-RNN during bodily interaction clarified the mechanism by which gaps in actional intentions between the human experimenter and the robot can be manifested as reaction forces between them.Comment: 12 pages, 8 figures, journal pape

SNARE-associated proteins and receptor trafficking

A wide variety of receptors that function on the cell surface are regulated, at least in part, through intracellular membrane trafficking including endocytosis, recycling and subsequent degradation. Soluble N-ethylmaleimide sensitive factor (NSF) attachment protein (SNAP) receptors (SNAREs) are essential molecules for the final step of intracellular membrane trafficking, i.e. fusion of transport vesicles with the target membrane. SNAREs on two opposing membranes form a trans-SNARE complex consisting of a four-helical bundle and drive a membrane fusion. The resultant cis-SNARE complex is disassembled through a process mediated by NSF and SNAPs. Cells contain families of SNAREs, and the interaction of cognate SNAREs at least contributes to the specificity of membrane fusion. The SNARE complex formation and dissociation are modulated by many SNARE-associated proteins at multiple steps including tethering, assembly and disassembly. Diverse molecular mechanisms, such as scaffolding, phosphorylation and ubiquitylation of SNARE proteins, and phosphoinositide production, are utilized for the modulation. In this review, we summarize recent progress in understanding the role of SNARE-associated proteins required for the endocytic recycling and degradation of epidermal growth factor receptor, transferrin receptor and integrins. We also discuss the physiological and pathological relevance of SNAREs and SNARE-associated proteins in the receptor trafficking

Mesenteric desmoid tumor of the interposed jejunal pouch after total gastrectomy

BACKGROUND: Desmoid tumor is a rare entity, and most desmoid tumors are located in abdominal wall or extra-abdominal tissues. Occurrence of desmoid tumor in mesentry is extremely rare. CASE PRESENTATION: we report a mesenteric desmoid tumor in a 73-years-old woman who had undergone total gastrectomy reconstructed with jejunal pouch interposition for gastric carcinoma. After 1 year, a tumor was originating from mesentery of the interposed jejunal pouch was identified, and the patient underwent resection of the large mass which was found to invade pancreas. Histological examination revealed desmoid tumor. CONCLUSION: Desmoid tumor is rare, and it was difficult for the differential diagnosis of desmoid tumor or recurrent tumor

Protumoral Effect of Angiotensin System.

Colorectal cancer (CRC) cells possess an angiotensin activation mechanism provided by the expression of renin and chymase. Renin expression is induced by a hyperglycemic condition. Since angiotensinogen is produced in the liver, CRC cells with angiotensin-activating machinery possess an advantage to metastasize to the liver. In human CRC cases, the diabetes-complicated patients show higher concentrations of renin and angiotensin-Ⅱ in the primary tumors, and a more progressed disease stage, especially, liver metastasis in association with HbA1c levels than those in the patients without diabetes. Concurrent treatment with anti-angiotensin and hypoglycemic agents shows a synergic effect of decreasing liver metastasis and improving the survival of diabetic mice in the CRC liver metastasis model. MAS1-angiotensin1-7 is a negative regulator of the AGTR1-angiotensin Ⅱ axis in breast cancer. Notably, MAS1 is overexpressed in triple negative breast cancer, which might be a novel molecular target for the treatment-refractory entity of breast cancer. Nuclear AGTR2 and intracellular angiotensin-Ⅱ play a role in anti-apoptotic and anti-oxidative stress properties. These functions of nuclear AGTR2 might mitigate "anti-tumoral side effects" of AGTR1 and angiotensin-Ⅱ system, which enhance mainly tumor progression. The effect of anti-angiotensin treatment such as ARB and blood sugar control as ab aseline management of many cancer patients needs to be examined in a clinical situation for prevention of RAS-induced tumor progression

Duodenoportal fistula caused by peptic ulcer after extended right hepatectomy for hilar cholangiocarcinoma

BACKGROUND: A fistula between the duodenum and the main portal vein near a peptic ulcer is extremely rare, and only two cases of duodenal ulcers have been reported in the past. CASE PRESENTATION: We report a 68-year-old man with a diagnosis of anemia who had a history of extended right hepatectomy for hilar cholangiocarcinoma 20 months previously. The first endoscopic examination revealed a giant peptic ulcer with active bleeding at the posterior wall of the duodenal bulbs, and hemostasis was performed. Endoscopic treatment and transarterial embolization were performed repeatedly because of uncontrollable bleeding from the duodenal ulcer. Nevertheless, he died of sudden massive hematemesis on the 20(th )hospital day. At autopsy, communication with the main portal vein and duodenal ulcer was observed. CONCLUSION: It should be borne in mind that the main portal vein is exposed at the front of the hepatoduodenal ligament in cases with previous extrahepatic bile duct resection

Role of CD10 in the Metastasis of Colorectal Cancer to the Liver.

CD10 is a widely expressed endopeptidase that is present in human colorectal cancer (CRC), which shows a high frequency of liver metastasis. CD10 expression in CRC cells is associated with liver metastasis in rodent models, and CD10 expression enhances the phosphorylation of epidermal growth factor (EGF) receptor (EGFR) and extracellular signalregulated kinase (ERK) l/2. Met-enkephalin (MENK), a CD10 substrate, activates its specific receptor δ-opioid receptor (DOR), which is expressed in CRCs. DOR is a partial agonist of ERK1/2, which suppresses EGF-induced phosphorylation of EGFR and ERK1/2. CD10 retains EGF-induced EGFR activation by degrading MENK. Paradoxically, CRCs express MENK at a high frequency. Since MENK suppresses T lymphocytes, CD10-expressing CRCs can escape from T-cell immunity without exhibiting auto-inhibition. CD10 is strongly associated with the metastasis of CRCs to the liver via an immunosuppressive mechanism. Additionally, CD10 may be an excellent serum marker for liver metastasis in patients with CRC and could represent a potential molecular target for antimetastatic treatment in patients with CRC

Radial alignment of microtubules through tubulin polymerization in an evaporating droplet

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Keya, J. J., Kudoh, H., Kabir, A. M. R., Inoue, D., Miyamoto, N., Tani, T., Kakugo, A., & Shikinaka, K. Radial alignment of microtubules through tubulin polymerization in an evaporating droplet. Plos One, 15(4), (2020): e0231352, doi:10.1371/journal.pone.0231352.We report the formation of spherulites from droplets of highly concentrated tubulin solution via nucleation and subsequent polymerization to microtubules (MTs) under water evaporation by heating. Radial alignment of MTs in the spherulites was confirmed by the optical properties of the spherulites observed using polarized optical microscopy and fluorescence microscopy. Temperature and concentration of tubulins were found as important parameters to control the spherulite pattern formation of MTs where evaporation plays a significant role. The alignment of MTs was regulated reversibly by temperature induced polymerization and depolymerization of tubulins. The formation of the MTs patterns was also confirmed at the molecular level from the small angle X-ray measurements. This work provides a simple method for obtaining radially aligned arrays of MTs.Fund receiver: Akira Kakugo Grant-in-Aid for Scientific Research on Innovative Areas (Grant Nos. JP24104004 and 18H05423) and a Grant-in-Aid for Scientific Research (A) (Grant No. 18H03673) from kaken. NO - The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

胃癌におけるクローディン4標的化によるシスプラチン化学療法感受性の向上

Claudins are major tight-junction proteins that mediate cellular polarity and differentiation. The present study investigated whether the 4D3 antibody to the human CLDN4 extracellular domain (that we previously established) is capable of modulating chemotherapeutic sensitivity in gastric cancer (GC). The results of the present study showed that CLDN4 was overexpressed in 137 of the 192 analyzed GC cases, and that CLDN4 expression was retained in tumors of a lower histological grade (more differentiated), and/or those that were caudal-type homeobox protein 2 (CDX2)-positive, but was reduced in more highly undifferentiated, and CDX2-negative GC cases. The study also compared the synergic effects of combining 4D3 with CDDP treatment and knocking down CLDN4 expression in MKN74 and TMK-1 human GC cells. Co-treatment with 4D3 increased anti-tumor effects of CDDP, whereas CLDN4 knockdown did not. In the TMK-1 cells, non-tight junction CLDN4 associated with integrin β1, increasing stem cell-associated proteins via FAK-c-SRC signals. The anti-tumoral effect of CDDP and 4D3 was examined in a nude mouse subcutaneous tumor model. In the two GC cell lines, concurrent treatment with 4D3 and CDDP synergistically inhibited cell proliferation and increased tumor necrosis and apoptosis to a greater degree than CDDP treatment alone. These findings suggest that 4D3 might increase chemotherapeutic sensitivity by evoking structural disintegration of tight-junction CLDN4 expressed in gastric cancer.博士（医学）・甲第713号・令和元年6月26日Copyright: Nishiguchi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0 https://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited