The distinct distribution of two Dictyostelium Talins

Although the distinct distribution of certain molecules along the anterior or posterior edge is essential for directed cell migration, the mechanisms to maintain asymmetric protein localization have not yet been fully elucidated. Here, we studied a mechanism for the distinct localizations of two Dictyostelium talin homologues, talin A and talin B, both of which play important roles in cell migration and adhesion. Using GFP fusion, we found that talin B, as well as its C-terminal actin-binding region, which consists of an I/LWEQ domain and a villin headpiece domain, was restricted to the leading edge of migrating cells. This is in sharp contrast to talin A and its C-terminal actin-binding domain, which co-localized with myosin II along the cell posterior cortex, as reported previously. Intriguingly, even in myosin II-null cells, talin A and its actin-binding domain displayed a specific distribution, co-localizing with stretched actin filaments. In contrast, talin B was excluded from regions rich in stretched actin filaments, although a certain amount of its actin-binding region alone was present in those areas. When cells were sucked by a micro-pipette, talin B was not detected in the retracting aspirated lobe where acto-myosin, talin A, and the actin-binding regions of talin A and talin B accumulated. Based on these results, we suggest that talin A predominantly interacts with actin filaments stretched by myosin II through its C-terminal actin-binding region, while the actin-binding region of talin B does not make such distinctions. Furthermore, talin B appears to have an additional, unidentified mechanism that excludes it from the region rich in stretched actin filaments. We propose that these actin-binding properties play important roles in the anterior and posterior enrichment of talin B and talin A, respectively, during directed cell migration

Estimation of articulated angle in six-wheeled dump trucks using multiple GNSS receivers for autonomous driving

Due to the declining birthrate and aging population, the shortage of labor in the construction industry has become a serious problem, and increasing attention has been paid to automation of construction equipment. We focus on the automatic operation of articulated six-wheel dump trucks at construction sites. For the automatic operation of the dump trucks, it is important to estimate the position and the articulated angle of the dump trucks with high accuracy. In this study, we propose a method for estimating the state of a dump truck by using four global navigation satellite systems (GNSSs) installed on an articulated dump truck and a graph optimization method that utilizes the redundancy of multiple GNSSs. By adding real-time kinematic (RTK)-GNSS constraints and geometric constraints between the four antennas, the proposed method can robustly estimate the position and articulation angle even in environments where GNSS satellites are partially blocked. As a result of evaluating the accuracy of the proposed method through field tests, it was confirmed that the articulated angle could be estimated with an accuracy of 0.1$^\circ$ in an open-sky environment and 0.7$^\circ$ in a mountainous area simulating an elevation angle of 45$^\circ$ where GNSS satellites are blocked.Comment: This is an electronic version of an article published in ADVANCED ROBOTICS, 35:23, 1376-1387, 2021. ADVANCED ROBOTICS is available online at: www.tandfonline.com/Article DOI; 10.1080/01691864.2019.161962

Strongly Blueshifted Phenomena Observed with {\it Hinode}/EIS in the 2006 December 13 Solar Flare

We present a detailed examination of strongly blueshifted emission lines observed with the EUV Imaging Spectrometer on board the {\it Hinode} satellite. We found two kinds of blueshifted phenomenon associated with the X3.4 flare that occurred on 2006 December 13. One was related to a plasmoid ejection seen in soft X-rays. It was very bright in all the lines used for the observations. The other was associated with the faint arc-shaped ejection seen in soft X-rays. The soft X-ray ejection is thought to be an MHD fast-mode shock wave. This is therefore the first spectroscopic observation of an MHD fast-mode shock wave associated with a flare.Comment: 18 pages, 1 table, 6 figures. ApJ, accepte

Current state of therapeutic development for rare cancers in Japan, and proposals for improvement

This article discusses current obstacles to the rapid development of safe and effective treatments for rare cancers, and considers measures required to overcome these challenges. In order to develop novel clinical options for rare cancers, which tend to remain left out of novel therapeutic development because of their paucity, efficient recruitment of eligible patients, who tend to be widely dispersed across the country and treated at different centers, is necessary. For this purpose, it is important to establish rare cancer registries that are linked with clinical studies, to organize a central pathological diagnosis system and biobanks for rare cancers, and to consolidate patients with rare cancers to facilities that can conduct clinical studies meeting international standards. Establishing an all‐Japan cooperative network is essential. Clinical studies of rare cancers have considerable limitations in study design and sample size as a result of paucity of eligible patients and, as a result, the level of confirmation of the efficacy and safety shown by the studies is relatively low. Therefore, measures to alleviate these weaknesses inherent to external conditions need to be explored. It is also important to reform the current research environment in order to develop world‐leading treatment for rare cancers, including promotion of basic research, collaboration between industry and academia, and improvement of the infrastructure for clinical studies. Collaboration among a wide range of stakeholders is required to promote the clinical development of treatment for rare cancers under a nationwide consensus

Large-Area Fluorescence and Electron Microscopic Correlative Imaging With Multibeam Scanning Electron Microscopy

Recent improvements in correlative light and electron microscopy (CLEM) technology have led to dramatic improvements in the ability to observe tissues and cells. Fluorescence labeling has been used to visualize the localization of molecules of interest through immunostaining or genetic modification strategies for the identification of the molecular signatures of biological specimens. Newer technologies such as tissue clearing have expanded the field of observation available for fluorescence labeling; however, the area of correlative observation available for electron microscopy (EM) remains restricted. In this study, we developed a large-area CLEM imaging procedure to show specific molecular localization in large-scale EM sections of mouse and marmoset brain. Target molecules were labeled with antibodies and sequentially visualized in cryostat sections using fluorescence and gold particles. Fluorescence images were obtained by light microscopy immediately after antibody staining. Immunostained sections were postfixed for EM, and silver-enhanced sections were dehydrated in a graded ethanol series and embedded in resin. Ultrathin sections for EM were prepared from fully polymerized resin blocks, collected on silicon wafers, and observed by multibeam scanning electron microscopy (SEM). Multibeam SEM has made rapid, large-area observation at high resolution possible, paving the way for the analysis of detailed structures using the CLEM approach. Here, we describe detailed methods for large-area CLEM in various tissues of both rodents and primates

Two Boosted Black Holes in Asymptotically de Sitter Space-Time - Relation between Mass and Apparent Horizon Formation -

We study the apparent horizon for two boosted black holes in the asymptotically de Sitter space-time by solving the initial data on a space with punctures. We show that the apparent horizon enclosing both black holes is not formed if the conserved mass of the system (Abbott-Deser mass) is larger than a critical mass. The black hole with too large AD mass therefore cannot be formed in the asymptotically de Sitter space-time even though each black hole has any inward momentum. We also discuss the dynamical meaning of AD mass by examining the electric part of the Weyl tensor (the tidal force) for various initial data.Comment: 15 pages, accepted for publication in PR

Tree of motility – A proposed history of motility systems in the tree of life

Motility often plays a decisive role in the survival of species. Five systems of motility have been studied in depth: those propelled by bacterial flagella, eukaryotic actin polymerization and the eukaryotic motor proteins myosin, kinesin and dynein. However, many organisms exhibit surprisingly diverse motilities, and advances in genomics, molecular biology and imaging have showed that those motilities have inherently independent mechanisms. This makes defining the breadth of motility nontrivial, because novel motilities may be driven by unknown mechanisms. Here, we classify the known motilities based on the unique classes of movement-producing protein architectures. Based on this criterion, the current total of independent motility systems stands at 18 types. In this perspective, we discuss these modes of motility relative to the latest phylogenetic Tree of Life and propose a history of motility. During the ~4 billion years since the emergence of life, motility arose in Bacteria with flagella and pili, and in Archaea with archaella. Newer modes of motility became possible in Eukarya with changes to the cell envelope. Presence or absence of a peptidoglycan layer, the acquisition of robust membrane dynamics, the enlargement of cells and environmental opportunities likely provided the context for the (co)evolution of novel types of motility

Research and development for accuracy improvement of neutron nuclear data on minor actinides

To improve accuracy of neutron nuclear data on minor actinides, a Japanese nuclear data project entitled “Research and development for Accuracy Improvement of neutron nuclear data on Minor ACtinides (AIMAC)” has been implemented. Several independent measurement techniques were developed for improving measurement precision at J-PARC/MLF/ANNRI and KURRI/LINAC facilities. Effectiveness of combining the independent techniques has been demonstrated for identifying bias effects and improving accuracy, especially in characterization of samples used for nuclear data measurements. Capture cross sections and/or total cross sections have been measured for Am-241, Am-243, Np-237, Tc-99, Gd-155, and Gd-157. Systematic nuclear data evaluation has also been performed by taking into account the identified bias effect. Highlights of the AIMAC project are outlined

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049