Computational Analysis of Dancing Cells

Collective cell migration is observed during morphogenesis, angiogenesis, and wound healing, and this type of cell migration also contributes to efficient metastasis in some kinds of cancers. Because collectively migrating cells are much better organized than a random assemblage of individual cells, there seems to be a kind of order in migrating clusters. Extensive research has identified a large number of molecules involved in collective cell migration, and these factors have been analyzed using dramatic advances in imaging technology. To date, however, it remains unclear how myriad cells are integrated as a single unit. Recently, we observed unbalanced collective cell migrations that can be likened to either precision dancing or awa-odori, Japanese traditional dancing similar to the style at Rio Carnival, caused by the impairment of the conformational change of JRAB/MICAL-L2. This review begins with a brief history of image-based computational analyses on cell migration, explains why quantitative analysis of the stylization of collective cell behavior is difficult, and finally introduces our recent work on JRAB/MICAL-L2 as a successful example of the multidisciplinary approach combining cell biology, live imaging, and computational biology. In combination, these methods have enabled quantitative evaluations of the “dancing style” of collective cell migration

賠償責任保険の費用保険化に伴う法的論点 : 従来型のファースト・パーティ型保険と従来型のサード・パーティ型保険の中間領域

加害者が存在する事故に関して、当該加害者に損害賠償責任が発生するか否かを問わずに、当該事故によって被害者に生じた損害の完全な回復を図るには、保険者が、従来型のファースト・パーティ型保険と従来型のサード・パーティ型保険の中間領域となる保険商品の開発や引受を進めていく必要がある。具体的には、加害者が保険契約者となる、被害者のためにするファースト・パーティ型保険と、被害者に生じた損害を加害者が補償することによって生じる、加害者の費用負担損害を填補するサード・パーティ型保険が考えられる。本稿では、この両類型の保険商品の開発や引受の推進にあたって障碍となり得る法的論点を検討した。その結果、被害者の故意による事故招致に関する免責条項の欠缺、保険法22条の(類推) 適用の可否、保険者による補償額に関する被害者との折衝の可否が、今後解決すべき論点であることが明確となった。departmental bulletin pape

The Effect of the Great East Japan Earthquake on the Stock Prices of Non-Life Insurance Companies

The Great East Japan Earthquake of March 11, 2011, incurred huge damages to Japan. This paper investigates how this earthquake influenced the value of Japanese insurance companies, especially non-life insurance companies. Our findings are as follows. (1) The stock prices of insurance companies decreased right after the earthquake. The spread of this decrease was less for the stock prices of non-life insurance companies than for those of life insurance companies. (2) The more capital buffer a non-life insurance company had, the higher the stock return. (3) In the Earthquake Insurance System on Dwelling Risks in Japan not only indemnifies seismic losses but also functions as a Japanese stock market stabilizer

Structure–function studies of ultrahigh molecular weight isoprenes provide key insights into their biosynthesis

Some plant trans-1,4-prenyltransferases (TPTs) produce ultrahigh molecular weight trans-1,4-polyisoprene (TPI) with a molecular weight of over 1.0 million. Although plant-derived TPI has been utilized in various industries, its biosynthesis and physiological function(s) are unclear. Here, we identified three novel Eucommia ulmoides TPT isoforms—EuTPT1, 3, and 5, which synthesized TPI in vitro without other components. Crystal structure analysis of EuTPT3 revealed a dimeric architecture with a central hydrophobic tunnel. Mutation of Cys94 and Ala95 on the central hydrophobic tunnel no longer synthesizd TPI, indicating that Cys94 and Ala95 were essential for forming the dimeric architecture of ultralong-chain TPTs and TPI biosynthesis. A spatiotemporal analysis of the physiological function of TPI in E. ulmoides suggested that it is involved in seed development and maturation. Thus, our analysis provides functional and mechanistic insights into TPI biosynthesis and uncovers biological roles of TPI in plants

JRAB shifts “dancing style” of cell clusters

In fundamental biological processes, cells often move in groups, a process termed collective cell migration. Collectively migrating cells are much better organized than a random assemblage of individual cells. Many molecules have been identified as factors involved in collective cell migration, and no one molecule is adequate to explain the whole picture. Here we show that JRAB/MICAL-L2, an effector protein of Rab13 GTPase, provides the “law and order” allowing myriad cells to behave as a single unit just by changing its conformation. First, we generated a structural model of JRAB/MICAL-L2 by a combination of bioinformatic and biochemical analyses and showed how JRAB/MICAL-L2 interacts with Rab13 and how its conformational change occurs. We combined cell biology, live imaging, computational biology, and biomechanics to show that impairment of conformational plasticity in JRAB/MICAL-L2 causes excessive rigidity and loss of directionality, leading to imbalance in cell group behavior. This multidisciplinary approach supports the concept that the conformational plasticity of a single molecule provides “law and order” in collective cell migration

C9orf72-derived arginine-rich poly-dipeptides impede phase modifiers

Nuclear import receptors (NIRs) not only transport RNA-binding proteins (RBPs) but also modify phase transitions of RBPs by recognizing nuclear localization signals (NLSs). Toxic arginine-rich poly-dipeptides from C9orf72 interact with NIRs and cause nucleocytoplasmic transport deficit. However, the molecular basis for the toxicity of arginine-rich poly-dipeptides toward NIRs function as phase modifiers of RBPs remains unidentified. Here we show that arginine-rich poly-dipeptides impede the ability of NIRs to modify phase transitions of RBPs. Isothermal titration calorimetry and size-exclusion chromatography revealed that proline:arginine (PR) poly-dipeptides tightly bind karyopherin-β2 (Kapβ2) at 1:1 ratio. The nuclear magnetic resonances of Kapβ2 perturbed by PR poly-dipeptides partially overlapped with those perturbed by the designed NLS peptide, suggesting that PR poly-dipeptides target the NLS binding site of Kapβ2. The findings offer mechanistic insights into how phase transitions of RBPs are disabled in C9orf72-related neurodegeneration