The Function of Sialidase Revealed by Sialidase Activity Imaging Probe

Sialidase cleaves sialic acid residues from glycans such as glycoproteins and glycolipids. In the brain, desorption of the sialic acid by sialidase is essential for synaptic plasticity, learning and memory and synaptic transmission. BTP3-Neu5Ac has been developed for sensitive imaging of sialidase enzyme activity in mammalian tissues. Sialidase activity in the rat hippocampus detected with BTP3-Neu5Ac increases rapidly by neuronal depolarization. It is presumed that an increased sialidase activity in conjunction with neural excitation is involved in the formation of the neural circuit for memory. Since sialidase inhibits the exocytosis of the excitatory neurotransmitter glutamate, the increased sialidase activity by neural excitation might play a role in the negative feedback mechanism against the glutamate release. Mammalian tissues other than the brain have also been stained with BTP3-Neu5Ac. On the basis of information on the sialidase activity imaging in the pancreas, it was found that sialidase inhibitor can be used as an anti-diabetic drug that can avoid hypoglycemia, a serious side effect of insulin secretagogues. In this review, we discuss the role of sialidase in the brain as well as in the pancreas and skin, as revealed by using a sialidase activity imaging probe. We also present the detection of influenza virus with BTP3-Neu5Ac and modification of BTP3-Neu5Ac.     

Hydrogel photocatalysts for efficient energy conversion and environmental treatment

Photocatalysts have attracted great research interest owing to their excellent properties and potential for simultaneously addressing challenges related to energy needs and environmental pollution. Photocatalytic particles need to be in contact with their respective media to exhibit efficient photocatalytic performances. However, it is difficult to separate nanometer-sized photocatalytic materials from reaction media later, which may lead to secondary pollution and a poor recycling performance. Hydrogel photocatalysts with a three-dimensional (3D) network structures are promising support materials for photocatalysts based on features such as high specific surface areas and adsorption capacities and good environmental compatibility. In this review, hydrogel photocatalysts are classified into two different categories depending on their elemental composition and recent progresses in the methods for preparing hydrogel photocatalysts are summarized. Moreover, current applications of hydrogel photocatalysts in energy conversion and environmental remediation are reviewed. Furthermore, a comprehensive outlook and highlight future challenges in the development of hydrogel photocatalysts are presented.     

Abscopal Effect of Frozen Autograft Reconstruction Combined with an Immune Checkpoint Inhibitor Analyzed Using a Metastatic Bone Tumor Model

We evaluated the abscopal effect of re-implantation of liquid nitrogen-treated tumor-bearing bone grafts and the synergistic effect of anti-PD-1 (programmed death-1) therapy using a bone metastasis model, created by injecting MMT-060562 cells into the bilateral tibiae of 6–8-week-old female C3H mice. After 2 weeks, the lateral tumors were treated by excision, cryotreatment using liquid nitrogen, excision with anti-PD-1 treatment, and cryotreatment with anti-PD-1 treatment. Anti-mouse PD-1 4H2 was injected on days 1, 6, 12, and 18 post-treatment. The mice were euthanized after 3 weeks; the abscopal effect was evaluated by focusing on growth inhibition of the abscopal tumor. The re-implantation of frozen autografts significantly inhibited the growth of the remaining abscopal tumors. However, a more potent abscopal effect was observed in the anti-PD-1 antibody group. The number of CD8+ T cells infiltrating the abscopal tumor and tumor-specific interferon-γ (IFN-γ)-producing spleen cells increased in the liquid nitrogen-treated group compared with those in the excision group, with no significant difference. The number was significantly higher in the anti-PD-1 antibody-treated group than in the non-treated group. Overall, re-implantation of tumor-bearing frozen autograft has an abscopal effect on abscopal tumor growth, although re-implantation of liquid nitrogen-treated bone grafts did not induce a strong T-cell response or tumor-suppressive effect.     

Lessons from a Minimal Genome: What Are the Essential Organizing Principles of a Cell Built from Scratch?

One of the primary challenges facing synthetic biology is reconstituting a living system from its component parts. A particularly difficult landmark is reconstituting a self-organizing system that can undergo autonomous chromosome compaction, segregation, and cell division. Here, we discuss how the syn3.0 minimal genome can inform us of the core self-organizing principles of a living cell and how these self-organizing processes can be built from the bottom up. The review underscores the importance of fundamental biology in rebuilding life from its molecular constituents.     

Silver(I)-Ion-Mediated Cytosine-Containing Base Pairs: Metal Ion Specificity for Duplex Stabilization and Susceptibility toward DNA Polymerases

Spectroscopic characterization of Ag^I-ion-mediated C-Ag^I-A and C-Ag^I-T base pairs found in primer extension reactions catalyzed by DNA polymerases was conducted. UV melting experiments revealed that C-A and C-T mismatched base pairs in oligodeoxynucleotide duplexes are specifically stabilized by Ag^I ions in 1:1 stoichiometry in the same manner as a C-C mismatched base pair. Although the stability of the mismatched base pairs in the absence of Ag^I ions is in the order C-A≈C-T>C-C, the stabilizing effect of Ag^I ions follows the order C-C>C-A≈C-T. However, the comparative susceptibility of dNTPs to Ag^I-mediated enzymatic incorporation into the site opposite templating C is dATP>dTTP≫dCTP, as reported. The net charge, as well as the size and/or shape complementarity of the metal-mediated base pairs, or the stabilities of mismatched base pairs in the absence of metal ions, would be more important than the stability of the metallo-base pairs in the replicating reaction catalyzed by DNA polymerases.     

Carbon radicals generated by solid polymers: Electron spin resonance spectroscopy for detection of species in water

Radicals generated in plastic medical devices (solid phase) by γ-rays or electron-beam irradiation during sterilization are known to cause oxidation of protein drugs, resulting in a loss or reduction in drug efficacy. The generation of radical species in water by the radical species in solid polymers has not been proved. Using electron spin resonance (ESR) spectroscopy, we confirm the generation of new radicals in water by γ-ray irradiated cyclic olefin polymers (COP). ESR measurements are obtained using 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) as a spin probe and 5-(2,2-dimethyl-1,3-propoxycyclophosphoryl)-5-methyl-1-pyrroline N-oxide (CYPMPO) as a spin trap, in which the irradiated COP was immersed. The ESR signals indicate the TEMPOL radicals decline over time, suggesting the generation of new radicals. Conversely, the characteristic ESR signals of the adduct formed by the reaction between CYPMPO and the hydroxyl radical are observed. Thus, hydroxyl radicals are generated because of the migration of the radicals from COP to water. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48604.     

Molecular Features and Clinical Management of Hereditary Gynecological Cancers

Hereditary gynecological cancers are caused by several inherited genes. Tumors that arise in the female reproductive system, such as ovaries and the uterus, overlap with hereditary cancers. Several hereditary cancer-related genes are important because they might lead to therapeutic targets. Treatment of hereditary cancers should be updated in line with the advent of various new methods of evaluation. Next-generation sequencing has led to rapid, economical genetic analyses that have prompted a concomitant and significant paradigm shift with respect to hereditary cancers. Molecular tumor profiling is an epochal method for determining therapeutic targets. Clinical treatment strategies are now being designed based on biomarkers based on tumor profiling. Furthermore, the National Comprehensive Cancer Network (NCCN) guidelines significantly changed the genetic testing process in 2020 to initially consider multi-gene panel (MGP) evaluation. Here, we reviewed the molecular features and clinical management of hereditary gynecological malignancies, such as hereditary breast and ovarian cancer (HBOC), and Lynch, Li–Fraumeni, Cowden, and Peutz–Jeghers syndromes. We also reviewed cancer-susceptible genes revealed by MGP tests.     

Generation of New Artificial Metalloproteins by Cofactor Modification of Native Hemoproteins

Heme can be removed from a number of native hemoproteins, thus forming corresponding apoproteins, each of which provides a site for binding of a metal complex. In one example, myoglobin, an O₂ storage protein, can be reconstituted with iron porphycene to dramatically enhance the O₂ affinity. Although it is known that myoglobin has poor enzymatic activity, the insertion of iron corrole or iron porphycene into apomyoglobin increases its H₂O₂-dependent peroxidase/peroxygenase activities. Furthermore, reconstitution with manganese porphycene promotes hydroxylation of an inert C H bond. It is also of interest to insert a non-porphyrinoid complex into an apoprotein. A cavity of apocytochrome c has been found to bind a diiron carbonyl complex, serving as a functional model of diiron hydrogenase. Aponitrobindin has a rigid β-barrel structure that provides an excellent cavity for covalently anchoring a metal complex. A rhodium complex embedded in the cavity of genetically modified nitrobindin has been found to promote stereoselective polymerization of phenylacetylene.     

Exploring the Minimal RNA Substrate of Flexizymes

Flexizymes are tRNA acylation ribozymes that have been successfully used to facilitate genetic code reprogramming. They are capable of charging acid substrates onto various tRNAs and tRNA analogues. However, their minimal RNA substrate has not been investigated. Here we have designed fluorescently labeled short RNAs corresponding to the four, three, and two bases (4bRNA, 3bRNA, 2bRNA) at the tRNA 3′-end and explored the minimal RNA substrate of flexizymes, dFx and eFx. 3bRNA was the observed minimal RNA substrate of the flexizymes, but the efficiency of acylation of this short RNA was two to three times lower than that of 4bRNA. The efficiency of acylation of 4bRNA was comparable with that of the microhelix, a 22-base RNA conventionally used as a tRNA analogue for analyzing acylation efficiency. We also compared the efficiencies of acylation of the microhelix and 4bRNA with various acid substrates. Thanks to the short length of 4bRNA, its acyl-4bRNA products exhibited larger mobility shifts in gel electrophoresis than those exhibited by acyl-microhelix products with every substrate tested. This indicated that 4bRNA was an ideal RNA substrate for analyzing the efficiency of acylation by flexizymes.