Structural insights into tetraspanin CD9 function

Umeda, R., Satouh, Y., Takemoto, M. et al. Structural insights into tetraspanin CD9 function. Nat Commun 11, 1606 (2020). https://doi.org/10.1038/s41467-020-15459-

Structural insights into the HBV receptor and bile acid transporter NTCP

B型肝炎ウイルスの受容体“胆汁酸輸送体”の立体構造を解明. 京都大学プレスリリース. 2022-05-18.Roughly 250 million people are infected with hepatitis B virus (HBV) worldwide, and perhaps 15 million also carry the satellite virus HDV, which confers even greater risk of severe liver disease. Almost ten years ago the HBV receptor was identified as NTCP (sodium taurocholate co-transporting polypeptide), which interacts directly with the first 48 amino acid residues of the N-myristoylated N-terminal preS1 domain of the viral large (L) protein. Despite the pressing need for therapeutic agents to counter HBV, the structure of NTCP remains unsolved. This 349-residue protein is closely related to human apical sodium-dependent bile acid transporter (ASBT), another member of the solute carrier family SLC10. Crystal structures have been reported of similar bile acid transporters from bacteria, and these models with ten transmembrane helices are believed to resemble strongly both NTCP and ASBT. Using cryo-electron microscopy we have solved the structure of NTCP bound to an antibody, clearly showing the transporter has no equivalent to the first transmembrane helix of other SLC10 models, leaving the N-terminus exposed on the extracellular face. Comparison of the different structures indicates a common mechanism of bile acid transport, but the NTCP structure also displays a pocket formed by residues known to interact with preS1, presenting new and enticing opportunities for structure-based drug design

Time-resolved serial femtosecond crystallography reveals early structural changes in channelrhodopsin

X線自由電子レーザーを用いて、光照射によるチャネルロドプシンの構造変化の過程を捉えることに成功. 京都大学プレスリリース. 2021-03-26.Channelrhodopsins (ChRs) are microbial light-gated ion channels utilized in optogenetics to control neural activity with light . Light absorption causes retinal chromophore isomerization and subsequent protein conformational changes visualized as optically distinguished intermediates, coupled with channel opening and closing. However, the detailed molecular events underlying channel gating remain unknown. We performed time-resolved serial femtosecond crystallographic analyses of ChR by using an X-ray free electron laser, which revealed conformational changes following photoactivation. The isomerized retinal adopts a twisted conformation and shifts toward the putative internal proton donor residues, consequently inducing an outward shift of TM3, as well as a local deformation in TM7. These early conformational changes in the pore-forming helices should be the triggers that lead to opening of the ion conducting pore

Protective Human Leucocyte Antigen Haplotype, HLA-DRB1*01-B*14, against Chronic Chagas Disease in Bolivia

Chronic Chagas disease consists of four different forms categorized on the basis of their clinical manifestations, namely; cardiac, digestive, cardiodigestive and indeterminate. In Latin America, there are 8–10 million seropositive persons who are at risk of, or have already developed serious clinical complications and who have limited access to effective treatment. The cardiac and digestive forms are characterized by tissue damage caused by persistent infection of Trypanosoma cruzi and are thought to be modulated by host immunity. In our large scale screening for chronic Chagas disease in Santa Cruz, Bolivia, hearts and colons of 229 seropositive patients were examined. We found 31.4% of patients had abnormal electrocardiograms (ECGs), 15.7% presented with megacolon, 5.2% had a combination of abnormal ECG and megacolon, and 58.1% were of indeterminate status. Previously, we attempted to ascertain whether parasite genetic polymorphism might account for the differences in clinical manefestations, by analyzing parasite DNA taken from the same study group (with the addition of a further 62 megacolon post-operational patients). We found no relationships between parasite lineages and clinical disease form. The present study reveals that host HLA polymorphisms associate with clinical manifestations of Chagas

Recent Results from LHD Experiment with Emphasis on Relation to Theory from Experimentalist’s View

he Large Helical Device (LHD) has been extending an operational regime of net-current free plasmas towardsthe fusion relevant condition with taking advantage of a net current-free heliotron concept and employing a superconducting coil system. Heating capability has exceeded 10 MW and the central ion and electron temperatureshave reached 7 and 10 keV, respectively. The maximum value of β and pulse length have been extended to 3.2% and 150 s, respectively. Many encouraging physical findings have been obtained. Topics from recent experiments, which should be emphasized from the aspect of theoretical approaches, are reviewed. Those are (1) Prominent features in the inward shifted configuration, i.e., mitigation of an ideal interchange mode in the configuration with magnetic hill, and confinement improvement due to suppression of both anomalous and neoclassical transport, (2) Demonstration ofbifurcation of radial electric field and associated formation of an internal transport barrier, and (3) Dynamics of magnetic islands and clarification of the role of separatrix

Assessing the association between care quality and household chore rules in residential care institutions in Japan

The performance of household chores by children in Japanese residential care institutions has been widely accepted as a practice that fosters children’s independence and self-sufficiency. However, children coming from neglectful or dysfunctional families often require sensitive, individualized care, which they did not receive from their family of origin. While a shift away from large-scale institutions has begun, with smaller units or group homes now accounting for 40% of all care institutions, it is not clear that family-like, individualized care has been achieved in these smaller group homes. This study involved 61 participants aged 10 to 15 years and their care workers from six residential care institutions in the greater Tokyo area. It explored what aspects of care quality were related to the presence of certain characteristics of traditional management-oriented care: fixed rules for household chores and lack of choice in daily living. Care workers were asked whether children washed their own dishes, did their own laundry, chose their own clothes when shopping, and had mandatory events to attend in the residential care institutions. Care quality was assessed using the Early Adolescent HOME (Home Observation for Measurement of Environment) developed for Japanese residential care institutions (EA-HOME-JP). The findings suggest that care workers should re-examine their intentions in setting and applying household chore rules while exploring which aspects of child care, including regulatory activities and modeling, should be emphasized in order to actualize family-like and individualized care in institutions

Room-temperature quantum spin Hall phase in laser-patterned few-layer 1T′- MoS2

The quantum spin Hall (QSH) phase is an important feature of two dimensional topological insulators and is typically observed at temperatures below 100 K. Here, the authors report the observation of a room temperature quantum spin Hall phase in few-atom-layer 1T′-MoS2 patterned onto the 2H semiconducting phase by low-power laser beam irradiation