Structural elucidation of a methylenation reagent of esters: synthesis and reactivity of a dinuclear titanium(iii) methylene complex

Transmetallation of a zinc methylene complex [ZnI(tmeda)](2)(mu-CH2) with a titanium(iii) chloride [TiCl3(tmeda)(thf)] produced a titanium methylene complex. The X-ray diffraction study displayed a dinuclear methylene structure [TiCl(tmeda)](2)(mu-CH2)(mu-Cl)(2). Treatment of an ester with the titanium methylene complex resulted in methylenation of the ester carbonyl to form a vinyl ether. The titanium methylene complex also reacted with a terminal olefin, resulting in olefin-metathesis and olefin-homologation. Cyclopropanation by methylene transfer from the titanium methylene proceeded by use of a 1,3-diene. The mechanistic study of the cyclopropanation reaction by the density functional theory calculations was also reported

Intravital imaging of orthotopic and ectopic bone

Bone homeostasis is dynamically regulated by a balance between bone resorption by osteoclasts and bone formation by osteoblasts. Visualizing and evaluating the dynamics of bone cells in vivo remain difficult using conventional technologies, including histomorphometry and imaging analysis. Over the past two decades, multiphoton microscopy, which can penetrate thick specimens, has been utilized in the field of biological imaging. Using this innovative technique, the in vivo dynamic motion of bone metabolism-related cells and their interactions has been revealed. In this review, we summarize previous approaches used for bone imaging and provide an overview of current bone tissue imaging methods using multiphoton excitation microscopy.Hashimoto K., Kaito T., Kikuta J., et al. Intravital imaging of orthotopic and ectopic bone. Inflammation and Regeneration 40, 26 (2020); https://doi.org/10.1186/s41232-020-00135-6

Coronagraphic Low Order Wave Front Sensor : post-processing sensitivity enhancer for high performance coronagraphs

Detection and characterization of exoplanets by direct imaging requires a coronagraph designed to deliver high contrast at small angular separation. To achieve this, an accurate control of low order aberrations, such as pointing and focus errors, is essential to optimize coronagraphic rejection and avoid the possible confusion between exoplanet light and coronagraphic leaks in the science image. Simulations and laboratory prototyping have shown that a Coronagraphic Low Order Wave-Front Sensor (CLOWFS), using a single defocused image of a reflective focal plane ring, can be used to control tip-tilt to an accuracy of 10^{-3} lambda/D. This paper demonstrates that the data acquired by CLOWFS can also be used in post-processing to calibrate residual coronagraphic leaks from the science image. Using both the CLOWFS camera and the science camera in the system, we quantify the accuracy of the method and its ability to successfully remove light due to low order errors from the science image. We also report the implementation and performance of the CLOWFS on the Subaru Coronagraphic Extreme AO (SCExAO) system and its expected on-sky performance. In the laboratory, with a level of disturbance similar to what is encountered in a post Adaptive Optics beam, CLOWFS post-processing has achieved speckle calibration to 1/300 of the raw speckle level. This is about 40 times better than could be done with an idealized PSF subtraction that does not rely on CLOWFS.Comment: 10 pages, 7 figures, accepted for publication in PAS

Chondrocyte-like cells in nucleus pulposus and articular chondrocytes have similar transcriptomic profiles and are paracrine-regulated by hedgehog from notochordal cells and subchondral bone

Objective: The nucleus pulposus (NP) comprises notochordal NP cells (NCs) and chondrocyte-like NP cells (CLCs). Although morphological similarities between CLCs and chondrocytes have been reported, interactions between CLCs and NCs remain unclear. In this study, we aimed to clarify regulatory mechanisms of cells in the NP and chondrocytes. Design: We performed single-cell RNA sequencing (scRNA-seq) analysis of the articular cartilage (AC) and NP of three-year-old cynomolgus monkeys in which NCs were present. We then performed immunohistochemical analysis of NP and distal femur. We added sonic hedgehog (SHH) to primary chondrocyte culture. Results: The scRNA-seq analysis revealed that CLCs and some articular chondrocytes had similar gene expression profiles, particularly related to GLI1, the nuclear mediator of the hedgehog pathway. In the NP, cell–cell interaction analysis revealed SHH expression in NCs, resulting in hedgehog signaling to CLCs. In contrast, no hedgehog ligands were expressed by chondrocytes in AC samples. Immunohistochemical analysis of the distal end of femur indicated that SHH and Indian hedgehog (IHH) were expressed around the subchondral bone that was excluded from our scRNA-seq sample. scRNA-seq data analysis and treatment of primary chondrocytes with SHH revealed that hedgehog proteins mediated an increase in hypoxia-inducible factor 1-alpha (HIF-1α) levels. Conclusion: CLCs and some articular chondrocytes have similar transcriptional profiles, regulated by paracrine hedgehog proteins secreted from NCs in the NP and from the subchondral bone in the AC to promote the HIF-1α pathway.Hagizawa H., Koyamatsu S., Okada S., et al. Chondrocyte-like cells in nucleus pulposus and articular chondrocytes have similar transcriptomic profiles and are paracrine-regulated by hedgehog from notochordal cells and subchondral bone. Frontiers in Cell and Developmental Biology 11, 1151947 (2023); https://doi.org/10.3389/fcell.2023.1151947

Antiferromagnetic structure of alkali metal superoxide CsO2_2

We have performed a powder neutron diffraction study on CsO$_2$, where the unpaired electron with $s=1/2$ in the $\pi^*$ orbital of the O$_2^-$ ion is responsible for the magnetism. The magnetic reflections 0 $\frac{1}{2}$ 0 and 0 $\frac{1}{2}$ 1 were observed below the N\'{e}el temperature of about 10 K. An antiferromagnetic structure with a propagation vector of (0 ,$\frac{1}{2}$, 0) and magnetic moments parallel to the $a$-axis is the most plausible. The magnitude of the ordered moment is about 0.2 $\mu_B$, which is considered to be strongly suppressed due to the one-dimensionality of the system. We propose a possible $\pi^*$ orbital order that can explain the obtained magnetic structure, and discuss its relation to the one-dimensionality

Anti-Siglec-15 antibody suppresses bone resorption by inhibiting osteoclast multinucleation without attenuating bone formation

Anti-resorptive drugs are widely used for the treatment of osteoporosis, but excessive inhibition of osteoclastogenesis can suppress bone turnover and cause the deterioration of bone quality. Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) is a transmembrane protein expressed on osteoclast precursor cells and mature osteoclasts. Siglec-15 regulates proteins containing immunoreceptor tyrosine-based activation motif (ITAM) domains, which then induce nuclear factor of activated T-cells 1 (NFATc1), a master transcription factor of osteoclast differentiation. Anti-Siglec-15 antibody modulates ITAM signaling in osteoclast precursors and inhibits the maturation of osteoclasts in vitro. However, in situ pharmacological effects, particularly during postmenopausal osteoporosis, remain unclear. Here, we demonstrated that anti-Siglec-15 antibody treatment protected against ovariectomy-induced bone loss by specifically inhibiting the generation of multinucleated osteoclasts in vivo. Moreover, treatment with anti-Siglec-15 antibody maintained bone formation to a greater extent than with risedronate, the first-line treatment for osteoporosis. Intravital imaging revealed that anti-Siglec-15 antibody treatment did not cause a reduction in osteoclast motility, whereas osteoclast motility declined following risedronate treatment. We evaluated osteoclast activity using a pH-sensing probe and found that the bone resorptive ability of osteoclasts was lower following anti-Siglec-15 antibody treatment compared to after risedronate treatment. Our findings suggest that anti-Siglec-15 treatment may have potential as an anti-resorptive therapy for osteoporosis, which substantially inhibits the activity of osteoclasts while maintaining physiological bone coupling.Tsukazaki H., Kikuta J., Ao T., et al. Anti-Siglec-15 antibody suppresses bone resorption by inhibiting osteoclast multinucleation without attenuating bone formation. Bone 152, 116095 (2021); https://doi.org/10.1016/j.bone.2021.116095

The subaru coronagraphic extreme AO (SCExAO) system: Wavefront control and detection of exoplanets with coherent light modulation in the focal plane

The Subaru Coronagraphic Extreme-AO (SCExAO) system is designed for high contrast coronagraphic imaging at small angular separations, and is scheduled to see first light on the Subam Telescope in early 2011. The wavefront control architecture for SCExAO is optimized for scattered light control and calibration at small angular separations, and is described in this paper. Key subsystems for the SCExAO wavefront control architecture have been successfully demonstrated, and we report results from these tests and discuss their role in the SCExAO system. Among these subsystems, a technique which can calibrate and remove static and slow speckles which traditionally limit high contrast detections is discussed. A visible light lab prototype system at Subam Telescope recently demonstrated speckle halo reduction to 2e-7 contrast within 2 2λ/D, and removal of static coherent speckles to 3e-9 contrast

In vivo dynamic analysis of BMP-2-induced ectopic bone formation

Bone morphogenetic protein (BMP)-2 plays a central role in bone-tissue engineering because of its potent bone-induction ability. However, the process of BMP-induced bone formation in vivo remains poorly elucidated. Here, we aimed to establish a method for intravital imaging of the entire process of BMP-2-induced ectopic bone formation. Using multicolor intravital imaging in transgenic mice, we visualized the spatiotemporal process of bone induction, including appearance and motility of osteoblasts and osteoclasts, angiogenesis, collagen-fiber formation, and bone-mineral deposition. Furthermore, we investigated how PTH1-34 affects BMP-2-induced bone formation, which revealed that PTH1-34 administration accelerated differentiation and increased the motility of osteoblasts, whereas it decreased morphological changes in osteoclasts. This is the first report on visualization of the entire process of BMP-2-induced bone formation using intravital imaging techniques, which, we believe, will contribute to our understanding of ectopic bone formation and provide new parameters for evaluating bone-forming activity.Hashimoto K., Kaito T., Furuya M., et al. In vivo dynamic analysis of BMP-2-induced ectopic bone formation. Scientific Reports 10, 4751 (2020); https://doi.org/10.1038/s41598-020-61825-2