Quantification of Oxygenation and Oxygen Consumption Rates in the Mouse Brain based on Tissue Oxygen Level-Dependent (TOLD) MRI

A non-invasive method to estimate oxygenation and oxygen (O2) consumption rates in mouse brain tissue based on T1-weighted tissue oxygen level-dependent (TOLD) MRI was developed. The aim of the present study was to estimate the kinetics of O2 in tissue in order to facilitate the planning of radiation therapy. The relationship between the proton T1 relaxation rate and O2 concentrations was examined in water and corn oil samples, which are models of the aqueous and lipidic phases of cell components. T1 maps of the mouse brain were obtained under breathing high oxygen concentration gas, carbogen (95% O2 + 5% CO2), or 100% O2, and shifts in the concentration of O2 from the physiological state in the brain were then estimated. Pseudo-TOLD signals in blood samples, hemoglobin, and myoglobin aqueous solutions under oxygenation were measured to examine the effects of heme iron on T1. O2 metabolism in mouse brains was evaluated by the enhancement/diminishment rates of the TOLD signal when the breathing gas was switched from air to carbogen or 100% O2 and when it was switched back to air. Carbogen or 100% O2 inhalation increased cortical O2 levels by 0.28 or 0.26 mmol/L, respectively. By analyzing the time course profile of the TOLD signal, the oxygenation rate, oxygenation level, and O2 consumption rate were successfully estimated. TOLD MRI has potential as a useful tool to estimate the quantitative indices of oxygenation and O2 consumption rates in brain tissue.journal articl

A mutation in DNA polymerase γ harbours a shortened lifespan and high sensitivity to mutagens in the filamentous fungus Neurospora crassa

A novel short lifespan mutant in N. crassa was screened and analyzed to better understand the mechanism involved in maintaining hyphal elongation in filamentous fungi. The mutant strain exhibited a reduced number of possible conidia passages and a shorter hyphal elongation limit. In addition, the mutant strain exhibited higher sensitivity to mutagens such as hydroxyurea (HU) and ultraviolet (UV) radiation. Based on these observations, we named the novel mutant "mutagen sensitive and short lifespan 1 (ms1)". The mutation responsible for the short lifespan and mutagen sensitivity in the ms1 strain was identified in DNA polymerase γ (mip-1:NCU00276). This mutation presumably changed the amino acid at position 814 in the polymerase domain from leucine to arginine (MIP-1 L814R). mtDNA depletion was observed in the ms1 strain, indicating that the mutation in mip-1 caused mtDNA instability. Furthermore, copy numbers for specific regions of mtDNA were preferentially decreased in the ms1 strain, and these regions were found to be near GC-rich hairpins or clusters of putative G-quadruplex sequences . These secondary structures in DNA sequences, along with HU and UV damage, can impede the progression of the replication fork. This suggests that MIP-1 L814R is more vulnerable to replication stresses than wild-type MIP-1. Our findings highlight the importance of stable mtDNA replication for continuous hyphal elongation and demonstrate that aberrant replication can shorten the lifespan of filamentous fungi.journal articl

Biological Nano Quantum Sensors, Quantum Technology-Based Hyperpolarized MRI/NMR, Quantum Biology, and Quantum Biotechnology

The emerging field of quantum life science combines principles from quantum physics and biology to study fundamental life processes at the molecular level. Quantum mechanics, which describes the properties of small particles, can help explain how quantum phenomena such as tunneling, superposition, and entanglement may play a role in biological systems. However, capturing these effects in living systems remains challenging due to dissipation and decoherence caused by the surrounding environment. We overview the current status of the quantum life sciences from technologies and topics in quantum biology. Technologies such as biological nano quantum sensors, quantum technology-based hyperpolarized MRI/NMR, high-speed 2D electronic spectrometers, and computer simulations are being developed to address these challenges. These interdisciplinary fields have the potential to revolutionize our understanding of living organisms and lead to advancements in genetics, molecular biology, medicine, and bioengineering.journal articl

Application of the spectral determination method to unified gamma-, beta- and X-ray spectra

So far we have developed the innovative radioactivity quantification technique of spectral determination method (SDM) based on the first principle that a γ-ray spectrum obtained for a sample is a linear superposition of individual spectra of the radioactive nuclides included in the sample. We have applied this method to spectra measured with Ge, NaI detectors and liquid scintillation counter (LSC) and demonstrated that the determination uncertainty of the SDM was better than those of previous peak analysis methods for the spectra obtained from a sample including 8 or 9 radionuclides. In the present study we extended the SDM to apply to a unified spectrum composed of LSC and Ge detector, and the number of nuclides has been increased to 40. The new SDM code was named as SDM-LG. We selected 40 radionuclides from possible radionuclides included in nuclear debris and radioactive wastes in the environment which were produced by the nuclear accident in Fukushima in March. 2011. We carried out LSC and Ge measurements for 17 and 7 nuclides, respectively. The rest of the standard spectra among the 40 nuclides have been derived by simulation calculations utilizing the Geant 4.10.3 Monte Carlo simulation tool kit. The derived LSC and Ge spectra for each nuclide were unified to a single spectrum and the 40 sets of the composed spectra were completed as a unified data base. We studied the determination accuracy of the SDM-LG analysis by examining a composed spectrum made of 40 radionuclides with equal intensities (Each has a radioactivity fraction of 2.5%.). The SDM result shows that the relative determination uncertainties of 35 nuclides are below 20%. It is also indicated that by removing 3 interfering nuclides the determination accuracy of the other 37 nuclides could be improved.journal articl

Time?lapse imaging of cells in spatially fractionated X?ray fields using a mini beam as an alternative to accelerator?based microbeams

Due to the small number of accelerator?based X?ray microbeam facilities in the world, their use for biological research purposes is limited. Thus, the development of alternative methods is of high importance for the understanding of X?ray microbeam radiation biology expansion and its future utility. In this study, we performed mini beam irradiation of cells using a lead (Pb) collimator as an alternative method to microbeams. Also, we employed human cervical carcinoma HeLa cells and hTERT?immortalized fibroblast BJ?1 cells that express fluorescence ubiquitination?based cell?cycle indicators (FUCCI). FUCCI labeling was useful in distinguishing irradiated from non?irradiated cells in the case of HeLa cells. Our imaging results clearly showed differences in the behavior of HeLa and BJ-1 cells in spatially heterogeneous radiation fields; in the case of HeLa cells, G2/M phase arrest cells in the cell population were clearly observed. The Pb sub?milli?collimators are a promising alternative to X?ray microbeams for radiobiology studies, and their combination with time?lapse imaging is a possible approach for investigating tissue responses in spatially non?uniform radiation fields.journal articl

Prevalence of Cataractous Changes in the Eyes and Chronic Inflammatory Changes in the Hands Among Spine Surgeons.

The impact of radiation exposure on cataracts and hand skin cancer in orthopaedic and spine surgeons remains understudied. This study aimed to investigate the prevalence of cataracts and chronic hand inflammation in orthopaedic and spine surgeons and to assess their association with radiation exposure.journal articl

The magnetism and elasticity of ε-FeOOH across the pressure-induced electronic spin transition

We conducted in-situ synchrotron X-ray experiments on iron oxyhydroxide ε-FeOOH to study the effects of the pressure-induced electronic spin transition on magnetism and elasticity. Polycrystalline ε-FeOOH was compressed in diamond anvil cells, and Mossbauer spectra and inelastic X-ray scattering were measured up to 120 and 49.9 GPa, respectively. On compression, the Mossbauer spectra showed a transition from a single magnetic sextet to a single doublet with the coexistence region 30?48 GPa, suggesting the low-spin state without magnetic ordering. The longitudinal elastic wave velocity V L calculated using the acoustic phonon dispersion exhibited a ~5% decrease at 38 GPa, which is almost the middle of the coexistence pressure region observed by Mossbauer absorption, indicating an elastic softening by the spin transition. The V L drop would be attributed to the elastically soft low-spin domain inferred by the large pressure dependence of the center shift of the low-spin doublet.journal articl

Heavy water toxicity via isotope effects: Stronger than high-dose radiation, neutralized by light water

Numerous enzymatic reactions involve hydrolysis, making water indispensable for sustaining life. Some water includes hydrogen isotopes, deuterium or tritium, with larger atomic weights. Heavy water consisting of deuterium is toxic to living organisms and induces cell death; however, the extent and underlying mechanisms of this toxicity remained elusive. Herein, we demonstrate that 100% heavy water triggers a remarkably heightened apoptotic response in human cells, compared to exposure to high-dose ionizing radiation. This pronounced effect of heavy water on cellular function may stem from the quantum-level mechanisms of kinetic isotope effects inherent to water isotopes, leading to a deceleration in enzymatic hydrolysis reactions. Notably, dilution of heavy water by approximately ten-fold with ordinary light water abolishes its isotope effect on enzymatic hydrolysis reactions, concomitant with the disappearance of DNA repair inhibition and cell death induction in human cells. These findings reveal that high concentrations of water isotopes containing heavier hydrogen have extreme cell death-inducing toxicity, yet this toxicity disappears upon dilution, thereby offering crucial insights into environmental considerations.journal articl

Effects of whole-body carbon-ion beam irradiation on bone marrow death in mice and an examination of candidates for protectors or mitigators against carbon-ion beam-induced bone marrow death

The present study examined the effects of whole-body carbon-ion beam irradiation on bone marrow death in mice and investigated whether compounds/materials, which were identified as efficient radio-protectors or mitigators against X-ray irradiation-induced bone marrow death, were also effective against the carbon-ion beam-induced death of mice. Amifostine and cysteamine were used as radio-protectors and zinc-containing heat-killed yeast (Zn-yeast) and γ-tocopherol-N,N-dimethylglycine ester (γTDMG) as radio-mitigators. Amifostine or cysteamine was intraperitoneally administered in a single injection of 1.95 mmol/kg body weight 30 min before whole-body carbon-ion beam irradiation. Zn-yeast or γTDMG was administered in a single intraperitoneal injection of 100 mg/kg body weight immediately after whole-body carbon-ion beam irradiation. The absorbed dose dependence of the 30-day survival rate after carbon-ion beam irradiation was analyzed. The biological effectiveness of carbon-ion beam irradiation (LD50/30 = 5.54 Gy) was estimated as 1.2 relative to X-ray irradiation (LD50/30 = 6.62 Gy). The dose reduction factors (DRF) of amifostine, cysteamine, Zn-yeast, and γTDMG estimated for carbon-ion beam irradiation were 1.75, 1.53, 1.16, and 1.15, respectively. Radio-protectors and -mitigators that were effective against photon irradiation also exhibited efficacy against carbon-ion beam irradiation; however, the DRF for carbon-ion beam irradiation was slightly smaller than that for photon irradiation. Based on the radio-protective effects of amifostine and cysteamine, the contribution of ROS/free radicals to carbon-ion beam-induced bone marrow death was 70?90% of that to photon irradiation. Since the suppression of tumor growth by carbon-ion beam irradiation was not inhibited by the treatment with γTDMG or Zn-yeast, both mitigators have potential as normal tissue-selective protectors in carbon-ion radiation therapy.journal articl

Super-competition as a Novel Mechanism of the Dose-rate Effect in Radiation Carcinogenesis: A Mathematical Model Study.

Data from animal experiments show that the radiation-related risk of cancer decreases if the dose rate is reduced, even though the cumulative dose is unchanged (i.e., a dose-rate effect); however, the underlying mechanism is not well understood. To explore factors underlying the dose-rate effect observed in experimental rat mammary carcinogenesis, we developed a mathematical model that accounts for cellular dynamics during carcinogenesis, and then examined whether the model predicts cancer incidence. A mathematical model of multistage carcinogenesis involving radiation-induced cell death and mutagenesis was constructed using differential equations. The mutation rate was changed depending on the dose rate. The model also considered competition among cells with various mutation levels. The main parameters of the model were determined using previous experimental data. The parameters of the model were consistent with experimental observations. A dose-rate effect on carcinogenesis became apparent when the relationship between dose rate and mutation rate was linear quadratic or quadratic. The dose-rate effect became prominent when cells with more mutations preferentially compensated for the radiation-induced death of cells with fewer mutations. The phenomenon by which mutated cells gain a competitive advantage over normal cells is known as super-competition. Here, we identified super-competition as a novel mechanism underlying the dose-rate effects on carcinogenesis. The data also confirmed the relevance of the shape of the relationship between dose rate and the mutation rate. Thus, this study provides new evidence for the mechanism underlying the dose-rate effect, which is important for predicting the cancer-related risks of low-dose-rate irradiation.journal articl