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Tumor cure with conventional fractionated radiotherapy is 65%, dependent on tumor cell-autonomous gradual buildup of DNA double-strand break (DSB) misrepair. Here we report that single-dose radiotherapy (SDRT), a disruptive technique that ablates more than 90% of human cancers, operates a distinct dual-target mechanism, linking acid sphingomyelinase-mediated (ASMase-mediated) microvascular perfusion defects to DNA unrepair in tumor cells to confer tumor cell lethality. ASMase-mediated microcirculatory vasoconstriction after SDRT conferred an ischemic stress response within parenchymal tumor cells, with ROS triggering the evolutionarily conserved SUMO stress response, specifically depleting chromatin-associated free SUMO3. Whereas SUMO3, but not SUMO2, was indispensable for homology-directed repair (HDR) of DSBs, HDR loss of function after SDRT yielded DSB unrepair, chromosomal aberrations, and tumor clonogen demise. Vasoconstriction blockade with the endothelin-1 inhibitor BQ-123, or ROS scavenging after SDRT using peroxiredoxin-6 overexpression or the SOD mimetic tempol, prevented chromatin SUMO3 depletion, HDR loss of function, and SDRT tumor ablation. We also provide evidence of mouse-to-human translation of this biology in a randomized clinical trial, showing that 24 Gy SDRT, but not 3x9 Gy fractionation, coupled early tumor ischemia/reperfusion to human cancer ablation. The SDRT biology provides opportunities for mechanism-based selective tumor radiosensitization via accessing of SDRT/ASMase signaling, as current studies indicate that this pathway is tractable to pharmacologic intervention., Introduction While tumor cure in patients with localized primary disease treated with conventional fractionated radiotherapy is approximately 65% (1), new image-guided radiotherapy that precisely targets tumors in 3D yields an [...]

The overall manganese oxidization states of the oxygen-evolving complex (OEC) in the [S.sub.0] and [S.sub.2] states are determined for methanol containing spinach photosystem II (PSII) membrane fragments. The analysis has shown that the [Mn.sub.4][O.sub.x]Ca cluster has taken part in the unique water splitting chemistry through the structural changes, of which one can be located within the cluster.

Electron paramagnetic resonance (EPR) study on Co(II)corrins Cob(II)ester(1+) and base-off B12r(2+) provides the first direct evidence for axial solvent ligation in polar solvents. EPR forms an excellent tool to analyze subtle changes in the electronic structure of Co(super II)-corrin systems, especially when they are supported by density functional computations.

The semiquninone radical anions B[Q.sup..-], N[Q.sup..-], V[K3.sup..-] and V[K1.sup..-] in frozen propanol solution is measured using pulsed Q-band electron nuclear double resonance spectroscopy. The hyperfine (hf) tensors study concluded that four solvent molecules are coordinated through hydrogen bonds to the quinone oxygens but in V[K3.sup..-] and V[K1.sup..-] some of these hydrogen bonds do not lie in the plane of the quinone.

Results reveal two types of manganese with zero-field splitting tensors at low temperatures in single crystals of concanavalin A. At room temperature, the crystals display one type of manganese. Temperature dependent electron paramagnetic resonance spectra suggest a two-state conformational equilibria at 200K absolute temperature.

The simulations of both strongly and weakly coupled protons, along with the known copper hyperfine couplings, were used to estimate and compare the spin density distribution in the various CuA centers. The largest sulfur spin density was found in M160T9, and the lowest was found in purpAz.

Copper histidine plays a pivotal role in biological systems, especially in the treatment of Menkes and Wilson diseases. W=-band (95 Ghz) pulsed EPR and electron nuclear double resonance (ENDOR) spectroscopic techniques are used to determine the hyperfine couplings of different protons of Cu(II)-histidine complexes in frozen solutions.

(super 55)MN pulse ENDOR spectra for the So and S2 states at Q-band frequency is reported. Numerical analysis of the spectra shows that all four Mn ions are magnetically coupled, allows a refinement of the hyperfine interaction (HFI) parameters for the S2 state and provides the first reliable HFI tensors for the S0 state.

Research into the impact of axial ligand mutation on the Cu(sub A) site in the recombinant water soluble fragment of subunit II of Thermus thermophilus cytochrome c oxidase ba3 is presented. It is concluded that the axial ligand has a small but significant impact on the spin distribution in the Cu(sub A) centre, reflecting on the ground-state wave function.