Chlamydial Infection-Dependent Synthesis of Sphingomyelin as a Novel Anti-Chlamydial Target of Ceramide Mimetic Compounds

The obligate intracellular bacterium Chlamydia trachomatis is the major causative agent of bacterial sexually transmitted diseases worldwide. In infected cells, the ceramide transport protein (CERT) is recruited to inclusions, where C. trachomatis replicates using host-synthesized ceramide. The ceramide is converted to sphingomyelin (SM) by a chlamydial infection-dependent SM synthesis (cidSM-synthesis) pathway, which occurs even in the absence of the SM synthases (SMS)-1 and -2 of host cells. The ceramide mimetic compound (1R,3S)-HPA-12 and the nonmimetic compound E16A, both of which are potent inhibitors of CERT, repressed the proliferation of C. trachomatis in HeLa cells. Unexpectedly, (1R,3R)-HPA-12, a ceramide mimetic compound that lacks CERT inhibitory activity, also exhibited potent anti-chlamydial activity. Using endogenous SMS-knockout mutant HeLa cells, we revealed that (1R,3R)-HPA-12 mildly inhibited cidSM-synthesis. In addition, LC-MS analysis revealed that (1R,3R)-HPA-12 is converted to a phosphocholine-conjugated metabolite in an infection-dependent manner. Imaging analysis with a fluorescent analog of ceramide suggested that cidSM-synthesis occurs in the bacterial bodies and/or inclusions. Collectively, these results suggested that (1R,3R)-HPA-12 exerts its anti-chlamydia activity not only as an inhibitor of cidSM-synthesis, but also via putative toxic effects of its phosphocholine adduct, which is most likely produced by the cidSM-synthesis route

Spinal Deformity and the Musculoskeletal Cohort Study of the General Older Population

Article信州医学雑誌 69(3) : 111-120(2021)departmental bulletin pape

Time-resolved photoelectron angular distributions from nonadiabatically aligned CO2 molecules with SX-FEL at SACLA

Weperformed time-resolved photoelectron spectroscopy of valence orbitals of alignedCO2 molecules using the femtosecond soft x-ray free-electron laser and the synchronized near-infrared laser. By properly ordering the individual single-shot ion images, we successfully obtained the photoelectron angular distributions (PADs) of theCO2 molecules aligned in the laboratory frame (LF). The simulations using the dipole matrix elements due to the time dependent density functional theory calculations well reproduce the experimental PADs by considering the axis distributions of the molecules. The simulations further suggest that, when the degrees of alignment can be increased up to \ue1 cos2 q\uf1 > 0.8, themolecular geometries during photochemical reactions can be extracted fromthe measured LFPADs once the accurate matrix elements are given by the calculations

Verification of the Effectiveness of University-Sponsored Internships

本研究の目的は，大学生を対象とした大学主催インターンシップの効果を学問・就職活動の方法が異なる文系・理系学生を軸に検証することである。大学教育と職業の接続の一つとしてインターンシップが拡充されているが，職業に関連した分野を学んでいる理系学生を対象としたインターンシップと一部を除き必ずしも職業に直結しない文系学生を対象としたインターンシップの効果が異なる結果となるのではないかと考えた。検証の結果，効果のひとつである就業観の醸成では，文系学生は肯定的に捉えている一方，理系学生は，否定的と異なる結果であった。「獲得能力」については，文系学生は肯定的，理系学生は否定的な評価となった。全般的に文系学生は，比較的肯定的な評価しているが，理系学生，一部そうではない認識をしていることが確認された。departmental bulletin pape

Fully gapped pairing state in spin-triplet superconductor UTe₂

The recently discovered superconductor UTe₂ is a promising candidate for spin-triplet superconductors, but the symmetry of the superconducting order parameter remains highly controversial. Here, we determine the superconducting gap structure by the thermal conductivity of ultraclean UTe₂ single crystals. We find that the a-axis thermal conductivity divided by temperature κ/T in zero-temperature limit is vanishingly small for both magnetic field H‖a and H‖c axes up to H/Hc₂ ∼ 0.2, demonstrating the absence of nodes around the a axis contrary to the previous belief. The present results, combined with the reduction of nuclear magnetic resonance Knight shift, indicate that the superconducting order parameter belongs to the isotropic Au representation with a fully gapped pairing state, analogous to the B phase of superfluid ³He. These findings reveal that UTe₂ is likely to be a long-sought three-dimensional strong topological superconductor, hosting helical Majorana surface states on any crystal plane

Natural ligand-nonmimetic inhibitors of the lipid-transfer protein CERT

Lipid transfer proteins mediate inter-organelle transport of membrane lipids at organelle contact sites in cells, playing fundamental roles in the lipidome and membrane biogenesis in eukaryotes. We previously developed a ceramide-mimetic compound as a potent inhibitor of the ceramide transport protein CERT. Here we develop CERT inhibitors with structures unrelated to ceramide. To this aim, we identify a seed compound with no ceramide-like structure but with the capability of forming a hydrogen-bonding network in the ceramide-binding START domain, by virtual screening of ~3 × 106 compounds. We also establish a surface plasmon resonance-based system to directly determine the affinity of compounds for the START domain. Then, we subject the seed compound to a series of in silico docking simulations, efficient chemical synthesis, affinity analysis, protein-ligand co-crystallography, and various in vivo assays. This strategy allows us to obtain ceramide-unrelated compounds that potently inhibited the function of CERT in human cultured cells

Astrometric VLBI observations of H2_2O masers in an extreme OH/IR star candidate NSV17351

Results of astrometric very long baseline interferometry (VLBI) observations towards an extreme OH/IR star candidate NSV17351 are presented. We used the VERA (VLBI Exploration of Radio Astrometry) VLBI array to observe 22\,GHz H$_2$O masers of NSV17351. We derived an annual parallax of 0.247$\pm$0.035 mas which corresponds to a distance of 4.05$\pm$0.59 kpc. By averaging the proper motions of 15 maser spots, we obtained the systemic proper motion of NSV17351 to be ($\mu_{\alpha}\cos{\delta}, \mu_{\delta}$)$^{\mathrm{avg}}$ $=$ ($-$1.19 $\pm$ 0.11, 1.30 $\pm$ 0.19) mas\,yr$^{-1}$. The maser spots spread out over a region of 20 mas $\times$ 30 mas, which can be converted to a spatial distribution of $\sim$80 au $\times$ $\sim$120 au at the source distance. Internal motions of the maser spots suggest an outward moving maser region with respect to the estimated position of the central star. From single dish monitoring of the H$_2$O maser emission, we estimate the pulsation period of NSV17351 to be 1122$\pm$24 days. This is the first report of the periodic activity of NSV17351, indicating that NSV17351 could have a mass of $\sim$4\,M$_{\odot}$. We confirmed that the time variation of H$_2$O masers can be used as a period estimator of variable OH/IR stars. Furthermore, by inspecting dozens of double-peaked H$_2$O maser spectra from the last 40 years, we detected a long-term acceleration in the radial velocity of the circumstellar matter to be $0.17\pm0.03$ km\,s$^{-1}$\,yr$^{-1}$ Finally, we determined the position and kinematics of NSV17351 in the Milky Way Galaxy and found that NSV17351 is located in an interarm region between the Outer and Perseus arms. We note that astrometric VLBI observations towards extreme OH/IR stars are useful samples for studies of the Galactic dynamics.Comment: Published in the Publications of the Astronomical Society of Japa