Self-assembling A6K peptide nanotubes as a mercaptoundecahydrododecaborate (BSH) delivery system for boron neutron capture t (BNCT)

Boron neutron capture therapy (BNCT) is a tumor selective therapy, the effectiveness of which depends on sufficient 10B delivery to and accumulation in tumors. In this study, we used self-assembling A6K peptide nanotubes as boron carriers and prepared new boron agents by simple mixing of A6K and BSH. BSH has been used to treat malignant glioma patients in clinical trials and its drug safety and availability have been confirmed; however, its contribution to BNCT efficacy is low. A6K nanotube delivery improved two major limitations of BSH, including absence of intracellular transduction and non-specific drug delivery to tumor tissue. Varying the A6K peptide and BSH mixture ratio produced materials with different morphologies—determined by electron microscopy—and intracellular transduction efficiencies. We investigated the A6K/BSH 1:10 mixture ratio and found high intracellular boron uptake with no toxicity. Microscopy observation showed intracellular localization of A6K/BSH in the perinuclear region and endosome in human glioma cells. The intracellular boron concentration using A6K/BSH was almost 10 times higher than that of BSH. The systematic administration of A6K/BSH via mouse tail vein showed tumor specific accumulation in a mouse brain tumor model with immunohistochemistry and pharmacokinetic study. Neutron irradiation of glioma cells treated with A6K/BSH showed the inhibition of cell proliferation in a colony formation assay. Boron delivery using A6K peptide provides a unique and simple strategy for next generation BNCT drugs

BPG4 regulates chloroplast development and homeostasis by suppressing GLK transcription factors and involving light and brassinosteroid signaling

葉緑体の発達を適正に制御する新しい因子を発見. 京都大学プレスリリース. 2024-01-23.Chloroplast development adapts to the environment for performing suitable photosynthesis. Brassinosteroids (BRs), plant steroid hormones, have crucial effects on not only plant growth but also chloroplast development. However, the detailed molecular mechanisms of BR signaling in chloroplast development remain unclear. Here, we identify a regulator of chloroplast development, BPG4, involved in light and BR signaling. BPG4 interacts with GOLDEN2-LIKE (GLK) transcription factors that promote the expression of photosynthesis-associated nuclear genes (PhANGs), and suppresses their activities, thereby causing a decrease in the amounts of chlorophylls and the size of light-harvesting complexes. BPG4 expression is induced by BR deficiency and light, and is regulated by the circadian rhythm. BPG4 deficiency causes increased reactive oxygen species (ROS) generation and damage to photosynthetic activity under excessive high-light conditions. Our findings suggest that BPG4 acts as a chloroplast homeostasis factor by fine-tuning the expression of PhANGs, optimizing chloroplast development, and avoiding ROS generation

A novel mitochondrial DnaJ/Hsp40 family protein BIL2 promotes plant growth and resistance against environmental stress in brassinosteroid signaling

Funding Information: Acknowledgments We thank Dr. Tsuyoshi Nakagawa (Shimane University) for the gift of the gateway vectors, pGWB2, pGWB80, pGWB5, and pGWB3. This work was supported in part by funding from the Program for Promotion of Basic Research Activities for Innovation Bioscience (PROBRAIN) to T.N. and T.A., and CREST, Japan Science and Technology Agency to T.N. and T.A.Plant steroid hormones, brassinosteroids, are essential for growth, development and responses to environmental stresses in plants. Although BR signaling proteins are localized in many organelles, i.e., the plasma membrane, nuclei, endoplasmic reticulum and vacuole, the details regarding the BR signaling pathway from perception at the cellular membrane receptor BRASSINOSTEROID INSENSITIVE 1 (BRI1) to nuclear events include several steps. Brz (Brz220) is a specific inhibitor of BR biosynthesis. In this study, we used Brz-mediated chemical genetics to identify Brz-insensitive-long hypocotyls 2-1D (bil2-1D). The BIL2 gene encodes a mitochondrial-localized DnaJ/Heat shock protein 40 (DnaJ/Hsp40) family, which is involved in protein folding. BIL2-overexpression plants (BIL2-OX) showed cell elongation under Brz treatment, increasing the growth of plant inflorescence and roots, the regulation of BR-responsive gene expression and suppression against the dwarfed BRI1-deficient mutant. BIL2-OX also showed resistance against the mitochondrial ATPase inhibitor oligomycin and higher levels of exogenous ATP compared with wild-type plants. BIL2 participates in resistance against salinity stress and strong light stress. Our results indicate that BIL2 induces cell elongation during BR signaling through the promotion of ATP synthesis in mitochondria.Peer reviewe

Dyson-Schwinger Equations: Density, Temperature and Continuum Strong QCD

Continuum strong QCD is the application of models and continuum quantum field theory to the study of phenomena in hadronic physics, which includes; e.g., the spectrum of QCD bound states and their interactions; and the transition to, and properties of, a quark gluon plasma. We provide a contemporary perspective, couched primarily in terms of the Dyson-Schwinger equations but also making comparisons with other approaches and models. Our discourse provides a practitioners' guide to features of the Dyson-Schwinger equations [such as confinement and dynamical chiral symmetry breaking] and canvasses phenomenological applications to light meson and baryon properties in cold, sparse QCD. These provide the foundation for an extension to hot, dense QCD, which is probed via the introduction of the intensive thermodynamic variables: chemical potential and temperature. We describe order parameters whose evolution signals deconfinement and chiral symmetry restoration, and chronicle their use in demarcating the quark gluon plasma phase boundary and characterising the plasma's properties. Hadron traits change in an equilibrated plasma. We exemplify this and discuss putative signals of the effects. Finally, since plasma formation is not an equilibrium process, we discuss recent developments in kinetic theory and its application to describing the evolution from a relativistic heavy ion collision to an equilibrated quark gluon plasma.Comment: 103 Pages, LaTeX, epsfig. To appear in Progress in Particle and Nuclear Physics, Vol. 4

Presence of the β-triketone herbicide tefuryltrione in drinking water sources and its degradation product in drinking waters

Triketone herbicides are becoming popular because of their herbicidal activity against sulfonylurea-resistant weeds. Among these herbicides, tefuryltrione (TFT) is the first registered herbicide for rice farming, and recently its distribution has grown dramatically. In this study, we developed analytical methods for TFT and its degradation product 2-chloro-4-methylsulfonyl-3-[(tetrahydrofuran-2-yl-methoxy) methyl] benzoic acid (CMTBA). TFT was found frequently in surface waters in rice production areas at concentrations as high as 1.9 μg/L. The maximum observed concentration was lower than but close to 2 μg/L, which is the Japanese reference concentration of ambient water quality for pesticides. However, TFT was not found in any drinking waters even though the source waters were purified by conventional coagulation and filtration processes; this was due to chlorination, which transforms TFT to CMTBA. The conversion rate of TFT to CMBA on chlorination was almost 100%, and CMTBA was stable in the presence of chlorine. Moreover, CMTBA was found in drinking waters sampled from household water taps at a similar concentration to that of TFT in the source water of the water purification plant. Although the acceptable daily intake and the reference concentration of CMTBA are unknown, the highest concentration in drinking water exceeded 0.1 μg/L, which is the maximum allowable concentration for any individual pesticide and its relevant metabolites in the European Union Drinking Directive

Is the default of 2 liters for daily per-capita water consumption appropriate? A nationwide survey reveals water intake in Japan

Two liters per day is generally applied as the default drinking-water intake rate for risk assessments, although evidence supporting this value is insufficient. This study aimed to reveal actual water intakes from tap water and other types of drinks, and to explore the relationships between these intakes. For this purpose, we conducted a nationwide Internet questionnaire survey. Tap water intake negatively correlated with bottled water and soft drink intakes, suggesting a mutually complementary relationship. We propose an index, potential Tap Water Intake (pTWI), calculated by adding soft drinks and bottled water to tap water intake. Mean per-capita tap water intake across the entire Japanese population was estimated at 1.28 L/d, whereas mean pTWI was estimated at 1.65 L/d. Two liters per day corresponds to the 88th percentile of tap water intake and to the 76th percentile of pTWI, and covers the intake of the majority of population in Japan. This rate should continue being used for the default in the Japanese population, but the rate to cover the tap water intake of almost the entire population would be higher: it was > 2.5 L/d

Contribution of tap water to chlorate and perchlorate intake: A market basket study

The contributions of water to total levels of chlorate and perchlorate intake were determined using food and water samples from a market basket study from 10 locations in Japan between 2008 and 2009. Foods were categorized into 13 groups and analyzed along with tap water. The average total chlorate intake was 333 (min. 193-max. 486) mu g/day for samples cooked with tap water. The contribution of tap water to total chlorate intake was as high as 47%-58%, although total chlorate intake was less than 32% of the tolerable daily intake, 1500 mu g/day for body weight of 50 kg. For perchlorate, daily intake from water was 0.7 (0.1-4.4) mu g/day, which is not high compared to the average total intake of 14 (2.5-84) mu g/day, while the reference dose (RfD) is 35 mu g/day and the provisional maximum tolerable daily intake (PMTDI) is 500 mu g/day for body weight of 50 kg. The highest intake of perchlorate was 84 mu g/day, where concentrations in foods were high, but not in water. The contribution of water to total perchlorate intake ranged from 0.5% to 22%, while the ratio of highest daily intake to RfD was 240% and that to PMTDI was 17%. Eight baby formulas were also tested - total chlorate and perchlorate intakes were 147 (42-332) mu g/day and 1.11 (0.05-4.5) mu g/day, respectively, for an ingestion volume of 1 L/day if prepared with tap water. (C) 2013 The Authors. Published by Elsevier B.V. All rights reserved