Effects of Roxadustat on Erythropoietin Production in the Rat Body

Anemia is a major complication of chronic renal failure. To treat this anemia, prolylhydroxylase domain enzyme (PHD) inhibitors as well as erythropoiesis-stimulating agents (ESAs) have been used. Although PHD inhibitors rapidly stimulate erythropoietin (Epo) production, the precise sites of Epo production following the administration of these drugs have not been identified. We developed a novel method for the detection of the Epo protein that employs deglycosylation-coupled Western blotting. With protein deglycosylation, tissue Epo contents can be quantified over an extremely wide range. Using this method, we examined the effects of the PHD inhibitor, Roxadustat (ROX), and severe hypoxia on Epo production in various tissues in rats. We observed that ROX increased Epo mRNA expression in both the kidneys and liver. However, Epo protein was detected in the kidneys but not in the liver. Epo protein was also detected in the salivary glands, spleen, epididymis and ovaries. However, both PHD inhibitors (ROX) and severe hypoxia increased the Epo protein abundance only in the kidneys. These data show that, while Epo is produced in many tissues, PHD inhibitors as well as severe hypoxia regulate Epo production only in the kidneys.     

Total synthesis of ecteinascidin 743

The total synthesis of ecteinascidin 743 (1), an extremely potent antitumor agent, has been accomplished. The synthesis features Ugi's 4CC reaction, intramolecular Heck reaction, phenol-aldehyde cyclization, and acid-induced intramolecular sulfide formation.     

Total synthesis of polyamine toxin HO-416b and Agel-489 using a 2-nitrobenzenesulfonamide strategy

Total synthesis of spider toxins HO-416b (1) and Agel-489 (2) was accomplished using the 2-nitrobenzenesulfonamide (Ns) group as both a protecting and activating group. In this strategy, the C-N bonds were constructed by alkylation of sulfonamides with alkyl halides or Mitsunobu reaction with the corresponding alcohol. Beginning with monoprotection of the symmetrical diamine, the construction of the backbone from diamine 3 was efficiently accomplished in 7 steps for 14 and 9 steps for 29. Removal of the Ns group while the substrate was attached to a novel solid support enabled the efficient isolation of this highly polar compound.     

Lepton flavor violating leptonic and semileptonic decays of charged leptons in the minimal supersymmetric standard model

We consider the leptonic and semileptonic (SL) lepton-flavor violating (LFV) decays of the charged leptons in the minimal supersymmetric standard model (MSSM) with right-handed neutrinos. The parameters of the MSSM model are determined in the framework of the minimal supersymmetric SO(10) GUT model assuming the minimal supergravity model of supersymmetry breaking. The free parameters of the model are constrained adopting the WMAP cold dark matter constraint and adjusting the neutrino oscillation data. So constrained, the SO(10) GUT model gives a definite prediction for the Dirac-neutrino Yukawa matrix, which induces all LFV effects in the MSSM model through renormalization group equations of soft SUSY breaking parameters. A very detailed numerical analysis has been made to define numerically all MSSM parameters necessary for the evaluation of the LFV amplitudes. The basic LFV amplitudes in MSSM were rederived and improved. The formalism for the evaluation of all SL LFV amplitudes is given. Numerical results for dominant SL LFV branching ratios, the anomalous magnetic moment of the muon and the ℓ→ℓ’γ branching ratios are given.     

Structure of dichlorine monoxide as studied by microwave spectroscopy. Determination of equilibrium structure by a modified mass dependence method

The microwave spectra of four isotopic species of dichlorine monoxide (OCl₂) have been observed, and the rotational constants have been obtained. The r_m structure for each isotopic species has been determined by Watson's method. The equilibrium structure has been estimated by taking proper averages of r_m structures to be $\text{r}{}_{\mathrm{e}}\text{(OCl) = 1.69587(7)}\text{A}\text{?}$ and ∠_eClOCl = 110.886(6)°. The general applicability and the merit of the present method for estimating the equilibrium structure are pointed out.     

Two-dimensional Wigner crystal in magnetic fields

Orbital magnetic moment and the frequency dependent conductivities of the Wigner crystal are examined in the harmonic approximation. The effects of scattering on the collective modes are also discussed.     

Molecular structure of phosgene as studied by gas electron diffraction and microwave spectroscopy: The rs,rm, and re structures

The microwave spectra of eight isotopic species of COCl₂ have been observed, and the following rotational constants have been obtained: An analysis of the rotational constants has resulted in the r_s and r_m structures. The equilibrium structure, r_e, has been estimated by combining the r_m parameters derived according to Watson's method and the r_e bond distances estimated in our recent electron-diffraction and spectroscopic studies to be $\text{r}{}_{\mathrm{e}}\text{(CO}\text{) = 1.1756 ± 0.0023}\text{A}\text{?}$, $\text{r}{}_{\mathrm{e}}\text{(CCl}\text{) = 1.7381 ± 0.0019}\text{A}\text{?}$, ∠_eClCCl = 111.79 ± 0.24°.     

Critical modes of one-dimensional fermion systems

Critical modes of one-dimensional fermion systems are examined by use of the renormalization group technique. Both strongly incommensurate and commensurate bands are treated. Both frequency and momentum dependence and the analytic property of the response functions are determined. It is stressed that for some region of coupling constants the model has anomalous dimensions, i.e. it has critical indices dependent on the coupling constants. The results are applied to predict the temperature dependence of the shift and relaxation of the nuclear magnetic resonances.