Effects of postural-control training with different sensory reweightings in a patient with body lateropulsion: a single-subject design study.

INTRODUCTION: Body lateropulsion (BL) is an active lateral tilt of the body during standing or walking that is thought to be affected by a lesion of the vestibulospinal tract (VST) and the subjective visual vertical (SVV) tilt. Interventions for BL have not been established. OBJECTIVE: We examined the effects of postural-control training with different sensory reweighting on standing postural control in a patient with BL. METHODS: The patient had BL to the left when standing or walking due to a left-side medullary and cerebellar infarct. This study was a single-subject A-B design with follow-up: Phase A was postural-control training with visual feedback; phase B provided reweighting plantar somatosensory information. Postural control, VST excitability, and SVV were measured. RESULTS: At baseline and phase A, the patient could not stand with eyes-closed on a rubber mat, but became able to stand in phase B. The mediolateral center of pressure (COP) position did not change significantly, but the COP velocity decreased significantly during phase B and the follow-up on the firm surface. VST excitability was lower on the BL versus the non-BL side, and the SVV deviated to the right throughout the study. CONCLUSION: Postural-control training with reweighting somatosensory information might improve postural control in a patient with BL.

Therapeutic potential of clinical-grade human induced pluripotent stem cell-derived cardiac tissues.

Objectives: To establish a protocol to prepare and transplant clinical-grade human induced pluripotent stem cell (hiPSC)-derived cardiac tissues (HiCTs) and to evaluate the therapeutic potential in an animal myocardial infarction (MI) model. Methods: We simultaneously differentiated clinical-grade hiPSCs into cardiovascular cell lineages with or without the administration of canonical Wnt inhibitors, generated 5- layer cell sheets with insertion of gelatin hydrogel microspheres (GHMs) (HiCTs), and transplanted them onto an athymic rat MI model. Cardiac function was evaluated by echocardiography and cardiac magnetic resonance imaging and compared with that in animals with sham and transplantation of 5-layer cell sheets without GHMs. Graft survival, ventricular remodeling, and neovascularization were evaluated histopathologically. Results: The administration of Wnt inhibitors significantly promoted cardiomyocyte (CM) (P < .0001) and vascular endothelial cell (EC) (P = .006) induction, which resulted in cellular components of 52.0 ± 6.1% CMs and 9.9 ± 3.0% ECs. Functional analyses revealed the significantly lowest left ventricular end-diastolic volume and highest ejection fraction in the HiCT group. Histopathologic evaluation revealed that the HiCT group had a significantly larger median engrafted area (4 weeks, GHM(-) vs HiCT: 0.4 [range, 0.2-0.7] mm2 vs 2.2 [range, 1.8-3.1] mm2; P = .005; 12 weeks, 0 [range, 0-0.2] mm2 vs 1.9 [range, 0.1-3.2] mm2; P = .026), accompanied by the smallest scar area and highest vascular density at the MI border zone. Conclusions: Transplantation of HiCTs generated from clinical-grade hiPSCs exhibited a prominent therapeutic potential in a rat MI model and may provide a promising therapeutic strategy in cardiac regenerative medicine.

Genetic analysis of tellurate reduction reveals the selenate/tellurate reductase genes ynfEF and the transcriptional regulation of moeA by NsrR in Escherichia coli.

Several bacteria can reduce tellurate into the less toxic elemental tellurium, but the genes responsible for this process have not yet been identified. In this study, we screened the Keio collection of single-gene knockouts of Escherichia coli responsible for decreased tellurate reduction and found that deletions of 29 genes, including those for molybdenum cofactor (Moco) biosynthesis, iron-sulphur biosynthesis, and the twin-arginine translocation pathway resulted in decreased tellurate reduction. Among the gene knockouts, deletions of nsrR, moeA, yjbB, ynbA, ydaS and yidH affected tellurate reduction more severely than those of other genes. Based on our findings, we determined that the ynfEF genes, which code for the components of the selenate reductase YnfEFGH, are responsible for tellurate reduction. Assays of several molybdoenzymes in the knockouts suggested that nsrR, yjbB, ynbA, ydaS and yidH are essential for the activities of molybdoenzymes in E. coli. Furthermore, we found that the nitric oxide sensor NsrR positively regulated the transcription of the Moco biosynthesis gene moeA. These findings provided new insights into the complexity and regulation of Moco biosynthesis in E. coli.

Noninnocent Ligand in Rhodium(III)-Complex-Catalyzed C-H Bond Amination with Tosyl Azide.

Six-coordinate rhodium(III) complexes coordinated by a planar trianionic ligand (L3-) are synthesized. One of the axial positions is occupied by chloride (Cl-), bromide (Br-), or iodide (I-), and another axial position is coordinated by a solvent molecule such as acetonitrile (AN), water (H2O), tetrahydrofuran (THF), or pyridine (PY) to complete an octahedral rhodium(III) center; [RhIII(L3-)(X)(Y)]- (1X/Y; X = Cl-, Br-, or I-, Y = AN, H2O, THF, or PY). Coordination of the AN, H2O, and THF ligands to the metal center is rather weak, so that these solvent molecules are easily replaced by PY to give [RhIII(L3-)(Cl)(PY)]-. In the electrochemical measurements, all complexes have two reversible redox couples based on the ligand-centered oxidation L3- to L•2- and to L-, as reflected by the very similar redox potentials regardless of the different axial ligands. The rhodium(III) complexes catalyze C-H bond amination of xanthene with tosyl azide (TsN3). Because the yields of the aminated product are nearly the same among the complexes, replacement of the axial solvent ligands with TsN3 readily occurs to give a nitrene-radical-bound rhodium(III) complex, [RhIII(L•2-)(N•Ts)(X)]-, as an active oxidant, which is generated by one-electron transfer from the trianionic L3- to the nitrene nitrogen atom. Generation of such a diradical intermediate was substantiated by the direct reaction of 1Cl/AN with TsN3 in the absence of the substrate (xanthene). In this case, a rhodium(III) iminosemiquinone complex, 2, was generated by the intramolecular reaction between the nitrene-radical moiety and the radical moiety of the ligand L•2-.

A novel occludin-targeting monoclonal antibody prevents hepatitis C virus infection in vitro.

Since hepatitis C virus (HCV) is thought to enter into host hepatocytes using the same cellular pathways regardless of the genotypes, the host factors are promising targets to prevent and treat HCV infection. Human occludin (hOCLN) is one representative entry factor, and its second extracellular loop (EC2) contributes to the species selectivity of HCV-susceptibility. However, the exact function of hOCLN during HCV entry remains unknown, and no hOCLN-targeting antibodies or synthetic drugs that prevent and treat HCV infection have yet been developed. Here we generated the anti-hOCLN-EC2 monoclonal antibody (mAb) 67-2, and demonstrated that it efficiently inhibited HCV infection in the HCV-permissive human cell line Huh7.5.1. We also showed, using three different culture systems of Huh7.5.1 cells, that this novel mAb is accessible to OCLN from the basolateral side of hepatocytes but not from the apical side. In addition, our Western blot analyses indicated that the established 67-2 mAb reacted not only with hOCLN but also with mouse OCLN, strongly suggesting that 67-2 does not recognize the human-specific amino acids in OCLN-EC2. Moreover, we revealed that the anti-hOCLN-EC2 mAb 67-2 showed no adverse effects on cell viability or the barrier function of tight junctions.

Correction: Catalytic C-H amination driven by intramolecular ligand-to-nitrene one-electron transfer through a rhodium(iii) centre.

Correction for 'Catalytic C-H amination driven by intramolecular ligand-to-nitrene one-electron transfer through a rhodium(iii) centre' by Daiki Fujita et al., Chem. Commun., 2017, 53, 4849-4852.

Catalytic C-H amination driven by intramolecular ligand-to-nitrene one-electron transfer through a rhodium(iii) centre.

Werner type six-coordinate rhodium(iii) complexes coordinated by a planar trianionic ligand and two axial aniline ligands are synthesised. The trianionic ligand behaves as a redox-active ligand to form a ligand radical species upon one-electron oxidation of the complex. The rhodium(iii) complexes catalyse C-H amination of external substrates such as xanthene with tosylazide as the nitrene source. DFT-calculation and kinetic deuterium isotope effects indicate that a di-radical rhodium(iii) complex formed by one-electron transfer from the redox-active ligand to the nitrene group works as a reactive intermediate to induce aliphatic C-H activation.

Transplantation of adipose tissue-derived stem cells improves cardiac contractile function and electrical stability in a rat myocardial infarction model.

The transplantation of adipose tissue-derived stem cells (ADSCs) improves cardiac contractility after myocardial infarction (MI); however, little is known about the electrophysiological consequences of transplantation. The purpose of this study was to clarify whether the transplantation of ADSCs increases or decreases the incidence of ventricular tachyarrhythmias (VT) in a rat model of MI. MI was induced experimentally by permanent occlusion of the left anterior descending artery of Lewis rats. ADSCs were harvested from GFP-transgenic rats, and were cultured until passage four. ADSCs (10×10(6)) resuspended in 100µL saline or pro-survival cocktail (PSC), which enhances cardiac graft survival, were injected directly into syngeneic rat hearts 1week after MI. The recipients of ADSCs suspended in PSC had a larger graft area compared with those receiving ASDCs suspended in saline at 1week post-transplantation (number of graft cells/section: 148.7±10.6 vs. 22.4±3.4, p<0.05, n=5/group). Thereafter, all ADSC recipients were transplanted with ASDCs in PSC. ADSCs were transplanted into infarcted hearts, and the mechanical and electrophysiological functions were assessed. Echocardiography revealed that ADSC recipients had improved contractile function compared with those receiving PSC vehicle (fractional shortening: 21.1±0.9 vs. 14.1±1.2, p<0.05, n≥12/group). Four weeks post-transplantation, VT was induced via in vivo programmed electrical stimulation. The recipients of ADSCs showed a significantly lower incidence of induced VT compared with the control (31.3% vs. 83.3%, p<0.05, n≥12/group). To understand the electrical activity following transplantation, we performed ex vivo optical mapping using a voltage sensitive dye, and found that ADSC transplantation decreased conduction velocity and its dispersion in the peri-infarct area. These results suggest that ADSC transplantation improved cardiac mechanical and electrophysiological functions in subacute MI.