1 alpha,25-Dihydroxyvitamin D3[1 alpha,25(OH)2D3], an active form of vitamin D, has roles in many biological phenomena such as calcium homeostasis and bone formation, which are thought to be mediated by the 1 alpha,25(OH)2D3 receptor (VDR), a member of the nuclear hormone receptor superfamily. However, the molecular basis for the actions of 1 alpha,25(OH)2D3 in bone formation, its role during development and VDR genetic polymorphisms for predicting bone mineral density are uncertain. To investigate the functional role of VDR, we generated mice deficient in VDR by gene targeting. We report here that in VDR null mutant mice, no defects in development and growth were observed before weaning, irrespective of reduced expression of vitamin D target genes. After weaning, however, mutants failed to thrive, with appearance of alopoecia, hypocalcaemia and infertility, and bone formation was severely impaired as a typical feature of vitamin D-dependent rickets type II (refs 8, 9). Unlike humans with this disease, most of the null mutant mice died within 15 weeks after birth, and uterine hypoplasia with impaired folliculogenesis was found in female reproductive organs. These defects, such as alopoecia and uterine hypoplasia, were not observed in vitamin D-deficient animals. The findings establish a critical role for VDR in growth, bone formation and female reproduction in the post-weaning stage.
Panosialins A and B were isolated as inhibitors of an alpha1,3-fucosyltransferase, Fuc-TVII, which is a key enzyme in the biosynthesis of selectin ligands, from culture broth of Streptomyces sp. Panosialins A and B inhibited the Fuc-TVII activity with IC50 values of 4.8 and 5.3 microg/ml, respectively. Panosialin A suppressed expression of selectin ligands on U937 cells, and inhibited the cell adhesion to immobilized E-selectin-immunoglobulin. Panosialins are the first reported Fuc-TVII inhibitors which can suppress the biosynthesis of selectin ligands and then inhibit selectin-mediated cell adhesion.
Enzymatic lactate/O2 biofuel cells (BFCs) are energy conversion systems in which enzymes oxidize lactate at a bioanode and reduce oxygen at a biocathode. These enzymes are highly safe toward humans, and highly selective for substrates. In addition, lactate is contained abundant in a human sweat. Thus, the lactate/O2 BFCs have been attracting attention as a next-generation wearable power source1). We have produced a paper-based lactate biofuel cell in which lactate oxidase (LOx) and a mediator are physically absorbed on MgO-templated carbon (MgOC) having mesopores suitable for enzyme2). By using MgOC for electrode, long-term stability may be improved because the elution of the enzyme is suppressed by entrapping the enzyme in the mesopore3). On the other hand, covalent immobilization of mediators and enzymes seems to be effective for further improvement of stability of the electrodes. We recently reported that poly(glycidyl methacrylate) (poly(GMA)) bearing pendant glycidyl groups, grafted on the surface of MgO-templated carbon (GMgOC), was useful for forming strong multipoint covalent bonds with amino functional groups on the surface of flavin adenine dinucleotide-dependent glucose dehydrogenase (FAD-GDH) molecules4). The stability of FAD-GDH-immobilized GMgOC electrode showed good stability with a simple immobilization scheme by suppressing elution of FAD-GDH from the electrode surface. In this study, we newly fabricated a paper-based lactate biofuel cell using a GMgOC electrode formed by screen printing. A lactate biofuel cell anode, in which Azure A, as a mediator, was covalently immobilized on the GMgOC. LOx was also immobilized in the GMgOC. We evaluated the output current and the stability of the electrode. The synthesis reaction of the GMgOC is shown in Fig. 1(a). MgOC was irradiated with an electron beem to generate radicals, and then glycidyl methacrylate was introduced to form GMgOC on the electrode surface. Polyvinylidene difluoride(PVdF) as a binder and N-methyl-2-pyrrolidinone(NMP) as a solvent were added to GMgOC as a carbon ink. The paper-based carbon electrodes were fabricated by screen printing. A carbon leads and MgOC ink was printed on a water-repellent paper substrate, successively. The AzureA as a mediator and LOx as an enzyme were dropped on the porous carbon electrode surface. Chronoamperometry was performed using the prepared bioanode. The measurement was performed by the three-electrode method using a platinum wire as the counter electrode and a saturated KCl/Ag/AgCl electrode as the reference electrode, respectively. The chlonoamperometry was performed in 1 mol dm-3 phosphate buffer containing 0.1 mol dm-3 lactate. The potential was set at 0.1 V vs. Ag/AgCl. Figure 1(b) shows the cyclic voltammetry of the GMgOC electode. A catalytic oxidation current was observed at a nobler potential than -0.1 V. The peak current value of the present enzyme electrode was larger than that of an enzyme electrode in which MgOC was used as the electrode material. The results indicated that the use of GMgOC will obtain a larger peak value because of immobilizing mediator and enzymes makes electrons to transport more efficiently to the electrode. A chronoamperograms using GMgOC and MgOC electrodes were measured at 0.1 V. Figure 1(c) shows that the current value of MgOC was 0.09 mA cm-2 after 30000 s, and that of GMgOC was 1.7 mA cm-2. It was found to exhibit that the current density was about twice as high as MgOC. It’s because, mediators and enzymes are immobilized by physical adsorption on the carbon surface when using MgOC, while elution of LOx could be suppressed by using GMgOC because the amino group of the enzyme shell and the epoxy group on the carbon surface are bonded successfully. Reference 1) E. Katz et al., J. Electroanal. Chem., 479 (1999) 64. 2) I. Shitanda et al., J. Electrochem. Soc, 166(12) (2019) B1063-B1068. 3) S. Tsujimura et al., Electrochemistry 83 (2015) 372. 4) I. Shitanda, T. Kato et al., Bull. Chem. Soc. Jpn., 93 (2020) 32. Acknowledgments This work was partially supported by JST-ASTEP Grant Number JPMJTS1513, JSPS Grant Number 17H02162 and Private University Research Branding Project (2017-2019) from Ministry of Education, Culture, Sports, Science and Technology, and Tokyo University of Science Grant for President's Research Promotion. Figure 1
Lactate concentration in sweat is closely related to exercise intensity. Thus, real-time monitoring of lactate concentration is extremely important for improving athlete training and health management. There are many reports for monitoring the change in the lactic acid concentration in sweat over a long period of time using a wearable lactate biosensor 1,2). For practical application of a wearable lactate biosensor for long-term monitoring, it is important to suppress elution of the enzyme from the electrode by simple enzyme immobilization scheme. Recently, we have reported that long-term stability of a glucose oxidase (GOD)-immobilized electrode was dramatically improved by introducing a poly(glycidyl methacrylate) on a mesoporous carbon, namely MgO-templated carbon (MgOC), which binds to a GOD by coavalent bonding scheme. In this study, we applied the method mentioned above to a printed lactate biosensor. A lactate oxidase (LOx) was immobilized on the electrode by covalent bonding with a poly(glycidyl methacrylate)-modified carbon surface. Firstly, radicals were introduced on the MgOC surface by electron beam irradiation, and glycidyl methacrylate (GMA) having an epoxy group was polymerized according to the previously reported scheme3). We referred the poly(GMA)-immobilized MgOC was “GMgOC” in this study. GMgOC and polyvinylidene fluoride (PVdF) were dispersed in N-methyl pyrrolidone (NMP) to prepare a graft polymerized carbon ink for printing. A printed electrode tips were fabricated by screen printing. Then, an enzyme-immobilized electrode was prepared by modifying 1,2-naphthoquinone as a mediator and lactate oxidase as an enzyme. The stability of the enzyme-immobilized electrode was evaluated by 10 cycles of cyclic voltammetry. The measurement was performed in a 1 mol dm-3 phosphate buffer (pH 7.0) containing 25 mmol dm-3 lactic acid with a three-electrode system. A platinum wire as a counter electrode, and a sat. KCl/Ag/AgCl electrode as a reference electrode were used. The maximum current density was observed at about 0.13 V vs. Ag/AgCl. Figure 1 shows the maximum current of the cyclic voltammogram plotted against the number of cycles during multiple sweeps. In case of the GMgOC, the current value retained 95.7% after 10 cycles, but it was 68.4% in the case of unmodified MgOC. By performing graft polymerization on the MgOC surface to fabricate the electrode, no significant change in the current value was observed. These results indicated that LOx was stably immobilized on the GMgOC surface without degeneration. Acknowledgements This work was partially supported by JST-ASTEP Grant Number JPMJTS1513, JSPS Grant Number 17H02162 and Private University Research Branding Project (2017-2019) from Ministry of Education, Culture, Sports, Science and Technology, and Tokyo University of Science Grant for President's Research Promotion. References 1) W. Jia, A. J. Bandodkar, G. Valdés-Ramírez, J.R. Windmiller, Z. Yang,J. Ramírez ,G. Chan, J. Wang, Analytical Chemistry, 85 (2013), 6553. 2) R.A.Escalona-Villalpando,E.Ortiz-Ortega,J.P.Bocanegra-Ugalde,Shelley,D.Minteer,J.Ledesma-García, L.G. Arriaga, Journal of Power Sources, 412 (2019),496-504. 3) I. Shitanda ,T. Kato ,R. Suzuki ,T. Aikawa ,Y. Hoshi ,M. Itagaki , and S. Tsujimura , Bulletin of the Chemical Society of Japan, 93 (2019), 32-36. Figure 1
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