Possible Involvement of the Upregulation of ΔNp63 Expression Mediated by HER2-Activated Aryl Hydrocarbon Receptor in Mammosphere Maintenance

Cancer stem cells (CSCs) contribute to the drug resistance, recurrence, and metastasis of breast cancers. Recently, we demonstrated that HER2 overexpression increases mammosphere formation via the activation of aryl hydrocarbon receptor (AHR). In this study, the objective was to identify the mechanism underlying mammosphere maintenance mediated by HER2 signaling-activated AHR. We compared the chromatin structure of AHR-knockout (AHRKO) HER2-overexpressing MCF-7 (HER2-5) cells with that of wild-type HER2-5 cells; subsequently, we identified TP63, a stemness factor, as a potential target gene of AHR. ΔNp63 mRNA and protein levels were higher in HER2-5 cells than in HER2-5/AHRKO cells. Activation of HER2/HER3 signaling by heregulin treatment increased ΔNp63 mRNA levels, and its induction was decreased by AHR knockdown in HER2-5 cells. The results of the chromatin immunoprecipitation assay revealed an interaction between AHR and the intronic region of TP63, which encodes ΔNp63. A luciferase reporter gene assay with the intronic region of TP63 showed that AHR expression increased reporter activity. Collectively, our findings suggest that HER2-activated AHR upregulates ΔNp63 expression and that this signaling cascade is involved in CSC maintenance in HER2-expressing breast cancers.     

Completely Chemically Synthesized Long DNA Can be Transcribed in Human Cells

Chemical ligation reaction of DNA is useful for the construction of long functional DNA using oligonucleotide fragments that are prepared by solid phase chemical synthesis. However, the unnatural linkage structure formed by the ligation reaction generally impairs the biological function of the resulting ligated DNA. We achieved the complete chemical synthesis of 78 and 258 bp synthetic DNAs via multiple chemical ligation reactions with phosphorothioate and haloacyl-modified DNA fragments. The latter synthetic DNA, coding shRNA for luciferase genes with a designed truncated SV promoter sequence, successfully induced the expected gene silencing effect in HeLa cells.     

Levee damage and bridge scour by 2019 typhoon Hagibis in Kanto Region,Japan

Typhoon Hagibis made landfall in Japan at 19:00 JST on 12th October 2019. The heavy rainfall caused by the typhoon was mostly concentrated within a 24-hour period; it brought devastating damage to eastern Japan. This report focuses on the flood-induced levee damage and bridge scour generated by the typhoon in the Kanto region. The levee breaches occurred mainly in the northern part of the region. They were concentrated along the Kuji and Naka Rivers and tributaries of the Tone and Arakawa Rivers. In most breached locations, the cause of the damage was the landward overtopping of the river water. Surface erosion on the slope of the protected side and/or slope failure on the protected side due to seepage-induced instability were the main causes of the levee breaches. Apart from the flooding induced by the inundation of the river water, inland flooding was also found. Damage to a river bridge due to local scour revealed the importance of considering the movement of sandbars in river channels, i.e., changes in the river flow conditions, when assessing the risks of bridge scour.     

Synthesis of hydrogels with a gradient crosslinking structure by electron beam radiation to an aqueous solution of poly(sodium acrylate)

Hydrogels were prepared by electron beam (EB) radiation to the aqueous solutions of poly(sodium acrylate) in the presence of potassium and ammonium peroxodisulfates. The effects of EB radiation dose, as well as polymer, and initiator concentrations on the formation of gels, were investigated. On the basis of the storage modulus, loss modulus, and complex viscosity of the isolated gels determined by rheological measurement, the relationship between the radiation conditions and the rheological properties of the gels was discussed. Furthermore, hydrogels with a gradient crosslinking structure in a depth direction were synthesized by controlling EB radiation dose.     

A V-Nitrogenase Variant Containing a Citrate-Substituted Cofactor

Nitrogenases catalyze the ambient reduction of N₂ and CO at its cofactor site. Herein we present a biochemical and spectroscopic characterization of an Azotobacter vinelandii V nitrogenase variant expressing a citrate-substituted cofactor. Designated VnfDGK^Cit, the catalytic component of this V nitrogenase variant has an αβ₂(δ) subunit composition and carries an 8Fe P* cluster and a citrate-substituted V cluster analogue in the αβ dimer, as well as a 4Fe cluster in the “orphaned” β-subunit. Interestingly, when normalized based on the amount of cofactor, VnfDGK^Cit shows a shift of N₂ reduction from H₂ evolution toward NH₃ formation and an opposite shift of CO reduction from hydrocarbon formation toward H₂ evolution. These observations point to a role of the organic ligand in proton delivery during catalysis and imply the use of different reaction sites/mechanisms by nitrogenase for different substrate reductions. Moreover, the increased NH₃/H₂ ratio upon citrate substitution suggests the possibility to modify the organic ligand for improved ammonia synthesis in the future.     

Solution-Processable Pure Green Thermally Activated Delayed Fluorescence Emitter Based on the Multiple Resonance Effect

Thermally activated delayed fluorescence (TADF) materials based on the multiple resonance (MR) effect are applied in organic light-emitting diodes (OLEDs), combining high color purity and efficiency. However, they are not fabricated via solution-processing, which is an economical approach toward the mass production of OLED displays. Here, a solution-processable MR-TADF material (OAB-ABP-1), with an extended π-skeleton and bulky substituents, is designed. OAB-ABP-1 is synthesized from commercially available starting materials via a four-step process involving one-shot double borylation. OAB-ABP-1 presents attractive photophysical properties, a narrow emission band, a high photoluminescence quantum yield, a small energy gap between S₁ and T₁, and low activation energy for reverse intersystem crossing. These properties are attributed to the alternating localization of the highest occupied and lowest unoccupied molecular orbitals induced by the boron, nitrogen, and oxygen atoms. Furthermore, to facilitate charge recombination, two novel semiconducting polymers with similar ionization potentials to that of OAB-ABP-1 are synthesized for use as interlayer and emissive layer materials. A solution-processed OLED device is fabricated using OAB-ABP-1 and the aforementioned polymers; it exhibits pure green electroluminescence with a small full-width at half-maximum and a high external quantum efficiency with minimum efficiency roll-off.     

Local coordination,electronic structure,and thermal quenching of Ce3+ in isostructural Sr2GdAlO5 and Sr3AlO4F phosphors

Sr₂GdAlO₅:Ce and Sr₃AlO₄F:Ce are isostructural phosphors in which the Ce³⁺ 4f-5d₁ transition can be efficiently excited by a photon with energy lower than 3.1 eV. Herein, we analyze the crystal chemistry of the Ce³⁺ local coordination, compare the thermal quenching behavior and construct the electronic structure of Ce³⁺ in them. The Rietveld refinement on two occupancy models suggests that Gd³⁺ only occupies the 8h site in Sr₂GdAlO₅; this provides a hint on the preferred occupancy of dopant Ce³⁺ in this site. The large crystal filed splitting of Ce_8h is mainly due to the fact that the 8h site is bonded to two oxygen with relatively short d_Sr/Gd-O and forms a quasi-square antiprism which experiences a large distortion. The Ce³⁺ 5d-4f luminescence in Sr₃AlO₄F is much more stable against thermal quenching than that in Sr₂GdAlO₅, as evidenced by the temperature-dependent luminescence intensity and luminescence decay studies. The energy of the O²⁻-Eu^3+/2+ and O²⁻-Ce^4+/3+ charge transfer as well as bandgap were estimated and the electronic structure of Ce³⁺ were constructed. A larger energy barrier ΔE_dC between the Ce³⁺ 5d₁ level and the conduction band bottom in Sr₃AlO₄F is seen from the Vacuum Referred Binding Energy (VRBE) diagrams which explains the higher thermal quenching temperature by thermal ionization model.     

Development of a frameless and armless stereotactic neuronavigation system with ultrasonographic registration

OBJECTIVE: We have developed a frameless stereotactic neuronavigation system that allows navigation during neurosurgical procedures through an image formed from integrating ultrasonography and preoperative magnetic resonance (MR) imaging and/or x-ray computed tomography. METHODS: The system consists of a ultrasound imaging scanner, a workstation with an image capture board, and an ultrasonic tracking sensor with a 5-MHz ultrasonographic transducer. The ultrasonic tracking sensor measures the position and orientation of the ultrasonographic transducer. The oblique plane of the MR/computed tomographic image corresponding to the ultrasound image is then displayed on the workstation monitor. A three-dimensional computer graphic representation of the integrated image is also reported as a preliminary test. For the patient-image registration, the coordinates of digitized and imaged markers on a specifically developed reference frame are used. The reference frame is noninvasive because it is not bolted but only fastened to the patient's head with silicon. RESULTS: Based on the findings from the clinical application of the system in three cases, the system was advantageous because of the surgical procedures could be controlled by intraoperative ultrasonography as well as by preoperative MR/computed tomographic images. Missing parts in the ultrasonogram were supplemented with preoperative MR/computed tomographic images. At other times, spatial positioning and visualization by ultrasonography were useful for identifying anatomical objects in the image. CONCLUSION: This preliminary study of the frameless integration of ultrasonography into stereotactic space demonstrated its clinical usefulness. We believe that the concept of pre- and intraoperative image-guided surgery presented here will find increasing use in the future.