Distinct predictive performance of Rac1 and Cdc42 in cell migration.

We propose a new computation-based approach for elucidating how signaling molecules are decoded in cell migration. In this approach, we performed FRET time-lapse imaging of Rac1 and Cdc42, members of Rho GTPases which are responsible for cell motility, and quantitatively identified the response functions that describe the conversion from the molecular activities to the morphological changes. Based on the identified response functions, we clarified the profiles of how the morphology spatiotemporally changes in response to local and transient activation of Rac1 and Cdc42, and found that Rac1 and Cdc42 activation triggers laterally propagating membrane protrusion. The response functions were also endowed with property of differentiator, which is beneficial for maintaining sensitivity under adaptation to the mean level of input. Using the response function, we could predict the morphological change from molecular activity, and its predictive performance provides a new quantitative measure of how much the Rho GTPases participate in the cell migration. Interestingly, we discovered distinct predictive performance of Rac1 and Cdc42 depending on the migration modes, indicating that Rac1 and Cdc42 contribute to persistent and random migration, respectively. Thus, our proposed predictive approach enabled us to uncover the hidden information processing rules of Rho GTPases in the cell migration

Long-term peritoneal dialysis and encapsulating peritoneal sclerosis in children

Encapsulating peritoneal sclerosis (EPS) is the most serious complication of long-term peritoneal dialysis (PD), with a mortality rate that exceeds 30%. There have been many reports of the incidence of EPS being strongly correlated to the duration of PD. Patients on PD for longer than 5 years, and especially those receiving this treatment for more than 8 years, should undergo careful and repeated surveillance for risk factors associated with the development of EPS. The development of ultrafiltration failure, a high dialysate/plasma creatinine ratio, as determined by the peritoneal equilibration test, peritoneal calcification, a persistently elevated C-reactive protein level, and severe peritonitis in patients on PD for longer than 8 years are signals that should prompt the clinician to consider terminating PD as a possible means of preventing the development of EPS. The impact of the newer, biocompatible PD solutions on the incidence of EPS has not yet been determined

Usability of detecting delivery errors during treatment of prostate VMAT with a gantry-mounted transmission detector

Volumetric‐modulated arc therapy (VMAT) requires highly accurate control of multileaf collimator (MLC) movement, rotation speed of linear accelerator gantry, and monitor units during irradiation. Pretreatment validation and monitoring of these factors during irradiation are necessary for appropriate VMAT treatment. Recently, a gantry mounted transmission detector “Delta4 Discover® (D4D)” was developed to detect errors in delivering doses and dose distribution immediately after treatment. In this study, the performance of D4D was evaluated. Simulation plans, in which the MLC position was displaced by 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 mm from the clinically used original plans, were created for ten patients who received VMAT treatment for prostate cancer. Dose deviation (DD), distance‐to‐agreement (DTA), and gamma index analysis (GA) for each plan were evaluated by D4D. These results were compared to the results (DD, DTA and GA) measured by Delta4 Phantom + (D4P). We compared the deviations between the planned and measured values of the MLC stop positions A‐side and B‐side in five clinical cases of prostate VMAT during treatment and measured the GA values. For D4D, when the acceptable errors for DD, DTA, and GA were determined to be ≤3%, ≤2 mm, and ≤3%/2 mm, respectively, the minimum detectable errors in the MLC position were 2.0, 1.5, and 1.5 mm based on DD, DTA, and GA respectively. The corresponding minimum detectable MLC position errors were 2.0, 1.0, and 1.5 mm, respectively, for D4P. The deviation between the planned and measured position of MLC stopping point of prostate VMAT during treatment was stable at an average of −0.09 ± 0.05 mm, and all GA values were above 99.86%. In terms of delivering doses and dose distribution of VMAT, error detectability of D4D was comparable to that of D4P. The transmission‐type detector “D4D” is thus suitable for detecting delivery errors during irradiation

Cell death and cell proliferation in cartilage layers in human anterior cruciate ligament tibial insertions after rupture

The purpose of this study is to investigate cellular responses and histological changes of cartilaginous layers in human anterior cruciate ligament (ACL) tibial insertions after rupture compared with those in normal insertions. Fully 16 tibial insertions of ruptured ACLs were obtained during primary ACL reconstructions. We also obtained 16 normal ACL tibial insertions from cadavers. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) to detect apoptosis, proliferating cell nuclear antigen (PCNA) staining, and histological examination were performed. The percentage of TUNEL-positive chondrocytes in ruptured ACL insertions (30.2 ± 15.6%) was higher than that in normal insertions (9.6 ± 5.8%). The percentage of PCNA-positive chondrocytes was significantly different between ruptured ACL insertions (19.9 ± 15.0%) and normal insertions (12.3 ± 7.3%). The average thickness of the cartilage layer, the glycosaminoglycan-stained area, and the number of chondrocytes per millimeter in ruptured ACL insertions was smaller than those in normal insertions. The decrease in the number of chondrocytes owing to an imbalance between cell death and cell proliferation in the ACL insertions after rupture, as compared with normal insertions, may lead to histological changes of the cartilage layer in the insertions. An in-depth understanding of injured ACL insertion may help elucidate the etiology of histological changes and the function and significance of the existence of the cartilage layer of insertion. This understanding may help in developing optimal treatment protocols for ACL injuries if apoptosis and cell proliferation are controlled

Toward understanding transcriptional regulatory networks in abiotic stress responses and tolerance in rice

長崎大学学位論文 [学位記番号]博（医歯薬）甲第1168号 [学位授与年月日]令和元年6月5

Dust from Comet 209P/LINEAR during its 2014 Return: Parent Body of a New Meteor Shower, the May Camelopardalids

We report a new observation of the Jupiter-family comet 209P/LINEAR during its 2014 return. The comet is recognized as a dust source of a new meteor shower, the May Camelopardalids. 209P/LINEAR was apparently inactive at a heliocentric distance rh = 1.6 au and showed weak activity at rh < 1.4 au. We found an active region of <0.001% of the entire nuclear surface during the comet's dormant phase. An edge-on image suggests that particles up to 1 cm in size (with an uncertainty of factor 3-5) were ejected following a differential power-law size distribution with index q=-3.25+-0.10. We derived a mass loss rate of 2-10 kg/s during the active phase and a total mass of ~5x10^7 kg during the 2014 return. The ejection terminal velocity of millimeter- to centimeter-sized particles was 1-4 m/s, which is comparable to the escape velocity from the nucleus (1.4 m/s). These results imply that such large meteoric particles marginally escaped from the highly dormant comet nucleus via the gas drag force only within a few months of the perihelion passage.Comment: 18 pages, 4 figures, accepted on 2014 December 11 for publication in the Astrophysical Journal Letter

Efficacy of glutathione for the treatment of nonalcoholic fatty liver disease: an open-label, single-arm, multicenter, pilot study

Background: Glutathione plays crucial roles in the detoxification and antioxidant systems of cells and has been used to treat acute poisoning and chronic liver diseases by intravenous injection. This is a first study examining the therapeutic effects of oral administration of glutathione in patients with nonalcoholic fatty liver disease (NAFLD). Methods: The study was an open label, single arm, multicenter, pilot trial. Thirty-four NAFLD patients diagnosed using ultrasonography were prospectively evaluated. All patients first underwent intervention to improve their lifestyle habits (diet and exercise) for 3 months, followed by treatment with glutathione (300 mg/day) for 4 months. We evaluated their clinical parameters before and after glutathione treatment. We also quantified liver fat and fibrosis using vibration-controlled transient elastography. The primary outcome of the study was the change in alanine aminotransferase (ALT) levels. Results: Twenty-nine patients finished the protocol. ALT levels significantly decreased following treatment with glutathione for 4 months. In addition, triglycerides, non-esterified fatty acids, and ferritin levels also decreased with glutathione treatment. Following dichotomization of ALT responders based on a median 12.9% decrease from baseline, we found that ALT responders were younger in age and did not have severe diabetes compared with ALT non-responders. The controlled attenuation parameter also decreased in ALT responders. Conclusions: This pilot study demonstrates the potential therapeutic effects of oral administration of glutathione in practical dose for patients with NAFLD. Large-scale clinical trials are needed to verify its efficacy. Trial registration: UMIN000011118 (date of registration: July 4, 2013)

Multi-Cellular Logistics of Collective Cell Migration

During development, the formation of biological networks (such as organs and neuronal networks) is controlled by multicellular transportation phenomena based on cell migration. In multi-cellular systems, cellular locomotion is restricted by physical interactions with other cells in a crowded space, similar to passengers pushing others out of their way on a packed train. The motion of individual cells is intrinsically stochastic and may be viewed as a type of random walk. However, this walk takes place in a noisy environment because the cell interacts with its randomly moving neighbors. Despite this randomness and complexity, development is highly orchestrated and precisely regulated, following genetic (and even epigenetic) blueprints. Although individual cell migration has long been studied, the manner in which stochasticity affects multi-cellular transportation within the precisely controlled process of development remains largely unknown. To explore the general principles underlying multicellular migration, we focus on the migration of neural crest cells, which migrate collectively and form streams. We introduce a mechanical model of multi-cellular migration. Simulations based on the model show that the migration mode depends on the relative strengths of the noise from migratory and non-migratory cells. Strong noise from migratory cells and weak noise from surrounding cells causes “collective migration,” whereas strong noise from non-migratory cells causes “dispersive migration.” Moreover, our theoretical analyses reveal that migratory cells attract each other over long distances, even without direct mechanical contacts. This effective interaction depends on the stochasticity of the migratory and non-migratory cells. On the basis of these findings, we propose that stochastic behavior at the single-cell level works effectively and precisely to achieve collective migration in multi-cellular systems