Etoposide-induced death comprises such nuclear events as the formation of topoisomerase II-DNA cleavable complex and cytosolic events including caspase activation. By first establishing the ...temporospatial death sequence triggered by etoposide in a neuronal cell line, MN9D overexpressing Bcl-X(L) (MN9D/Bcl-X(L)) or control vector (MN9D/Neo), we examined whether formation of this complex is primarily responsible for cell death and at which strategic points and how Bcl-X(L) blocks etoposide-induced neuronal death. Etoposide induced death that was dependent on caspase, cycloheximide, and calpain in MN9D/Neo cells. Etoposide also induced death in enucleated MN9D/Neo cells, although this was less severe. The level of topoisomerase II-DNA cleavable complex reached at a maximum of 2 hr after etoposide treatment was identical in MN9D/Neo and MN9D/Bcl-X(L) cells. In MN9D/Neo cells, cytochrome c release into the cytosol and caspase activation occurred as early as 2 hr and 3-6 hr after etoposide treatment, respectively. Etoposide-induced DNA laddering potentially via caspase appeared as early as 12 hr after drug treatment, followed by nuclear swelling in MN9D/Neo cells (>18-20 hr). Subsequently, nuclear condensation started by 24-28 hr and became apparent thereafter. All of these events except for nuclear swelling were substantially blocked in MN9D/Bcl-X(L). At the later stage of cell death (<32-36 hr), a specific cleavage of Bax and fodrin appeared that was completely blocked by calpain inhibitor or by Bcl-X(L). Taken together, our data suggest that Bcl-X(L) prevents etoposide-induced neuronal death by exerting its anticaspase and anticalpain effect on cellular events after the formation of topoisomerase II-DNA cleavable complex that may not be a major contributor to cell death.
We report a de Haas-van Alphen (dHvA) oscillation study on IrTe2 single crystals showing complex dimer formations. By comparing the angle dependence of dHvA oscillations with band structure ...calculations, we show distinct Fermi surface reconstruction induced by a 1/5-type and a 1/8-type dimerizations. This verifies that an intriguing quasi-two-dimensional conducting plane across the layers is induced by dimerization in both cases. A phase transition to the 1/8 phase with higher dimer density reveals that local instabilities associated with intra- and interdimer couplings are the main driving force for complex dimer formations in IrTe2.
The temperature (\(T\)) dependence of the optical conductivity spectra \(\sigma(\omega)\) of a single crystal SrRuO\(_3\) thin film is studied over a \(T\) range from 5 to 450 K. We observed ...significant \(T\) dependence of the spectral weights of the charge transfer and interband \(d\)-\(d\) transitions across the ferromagnetic Curie temperature (\(T_c\) ~ 150 K). Such \(T\) dependence was attributed to the increase in the Ru spin moment, which is consistent with the results of density functional theory calculations. \(T\) scans of \(\sigma(\Omega, T)\) at fixed frequencies \(\Omega\) reveal a clear \(T^2\) dependence below \(T_c\), demonstrating that the Stoner mechanism is involved in the evolution of the electronic structure. In addition, \(\sigma(\Omega, T)\) continues to evolve at temperatures above \(T_c\), indicating that the local spin moment persists in the paramagnetic state. This suggests that SrRuO\(_3\) is an intriguing oxide system with itinerant ferromagnetism.
Mitosenes of both the pyrrolo- and pyrido1,2-aindole type have been prepared via modification of these heterotricyclic compounds. Several mitosenes have been studied for their reactions with ...nucleophiles under reductive conditions. The results of these experiments show that the biological activity of mitosenes is based on the mechanism of bioreductive activation. When both leaving groups at C-1 and C-10 in the mitosene are the same, the nucleophile preferably adds to C-10 under reductive conditions. All mitosenes were studied for their biological activities in vitro against L1210, WiDr, and A204. On the basis of these results a selection of three mitosenes was made for a more detailed biological evaluation. Several tumor model systems were used, viz. P388, human tumor xenografts, MAC 13, and MAC 16. The results of these studies show that mitosenes have a more limited range of activities than mitomycin C. Surprisingly, the in vivo activities of mitosene diol 8b and mitosene diacetate 10b against the gastric human tumor xenograft GXF 97 were very high and comparable with that of mitomycin C.
Acetohydroxy acid isomeroreductase (AHIR) is involved in the biosynthetic pathway of branched‐chain amino acids in microorganisms and plants. AHIR from Pseudomonas aeruginosa has been overexpressed ...in Escherichia coli and crystallized at 297 K using potassium/sodium tartrate as a precipitant. X‐ray diffraction data have been collected to 2.0 Å resolution at 100 K using synchrotron radiation. The crystals belong to the cubic space group P213, with unit‐cell parameters a = b = c = 184.38 Å, α = β = γ = 90°. Six monomers are present in the asymmetric unit, giving a VM of 2.34 Å3 Da−1 and a solvent content of 47.4%.
It has been recently reported (S. Lee et al., Nature Materials 12, 392, 2013) that superlattices where layers of the 8% Co-doped BaFe2As2 superconducting pnictide are intercalated with non ...superconducting ultrathin layers of either SrTiO3 or of oxygen-rich BaFe2As2, can be used to control flux pinning, thereby increasing critical fields and currents, without significantly affecting the critical temperature of the pristine superconducting material. However, little is known about the electron properties of these systems. Here we investigate the electrodynamics of these superconducting pnictide superlattices in the normal and superconducting state by using infrared reflectivity, from THz to visible range. We find that multi-gap structure of these superlattices is preserved, whereas some significant changes are observed in their electronic structure with respect to those of the original pnictide. Our results suggest that possible attempts to further increase the flux pinning may lead to a breakdown of the pnictide superconducting properties.
Quinolinic acid phosphoribosyltransferase (NadC; EC 2.4.2.19) is the key enzyme of NAD+ biosynthesis in both prokaryotes and eukaryotes. NadC catalyzes the decarboxylation of quinolinic acid (QA) to ...produce nicotinic acid mononucleotide (NAMN), an intermediate in NAD synthesis. NadCs of Helicobacter pylori appeared to be a hexamer during the purification procedure. Three different complexes of NadC, with QA, NAMN and phthalic acid (PA), an analogue of QA, were crystallized at 294 ± 1 K using the hanging‐drop vapour‐diffusion method. The QA complex crystal was found to belong to space group P41212, with unit‐cell parameters a = b = 148.8, c = 145.7 Å, α = β = γ = 90°. Diffraction data were collected from the NadC–substrate and NadC–substrate analogue complexes to resolutions of 2.3 Å (QA), 2.8 Å (PA) and 3.3 Å (NAMN) using synchrotron X‐ray radiation.
This paper presents a design method of transparency optimized feedback controller with robustness for a parallel 6-DOF haptic system. A disturbance observer is employed to eliminate coupling effects ...that exist in a mechanically coupled structure. A performance index for the transparency is defined by admittance matching, and by solving the H/sub 2/ optimal problem. The optimal solution that minimizes the performance index is obtained.
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