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Abstract Background Thiopurines continue to play an important role in the treatment of inflammatory bowel disease (IBD). It is well known that thiopurines can cause several adverse reactions. Especially, hematopoietic toxicity may lead to severe agranulocytosis. In a previous prospective study, we investigated the relationship between inosine triphosphate pyrophosphatase (ITPA) c.94c > a polymorphism, 6-thioguanine nucleotide (6-TGN) concentration and toxicity. Methods To clarify the cause of thiopurine toxicity, we analysed nucleoside disphosphate-linked moiety X-type motif 15 (NUDT15) gene polymorphisms, i.e., R139C, V18I, and V19_V19insGV, and measured 6-mercaptopurines and 6-methylmercaptopurines (6-MMP) using the archived blood samples collected from 49 IBD patients for our previous study. Results The ITPA c.94c > a polymorphism was detected in 19 patients (38.7%, all heterozygous). The R139C polymorphism was found in 10 patients (20.4%, 1 homozygous, 9 heterozygous), V18_V19insGV in 7 patients (14.3%, all heterozygous), and V18I in 2 patients (4.08%, all heterozygous). Although R139C was more strongly associated with leukopenia than c.94c > a, there were no significant correlations with 6-TGN and 6-MMP levels, as for c.94c > a. The leukopenia incidence rates for each gene polymorphism were 0% in those with all wild-type genes, 21.4% for c.94c > a only, 42.9% for NUDT15 polymorphism (s) only, and 80.0% for both polymorphisms. Conclusions All cases of leukopenia were associated with ITPA c.94c > a and/or polymorphism of NUDT15 and the risk of developing leukopenia was synergistically increased by ITPA and NUDT15 gene polymorphism. However, there was no association between the level of azathioprine metabolites and these polymorphisms.

Ternary metal nitrides are a promising class of functional materials, but their variety has been limited by the challenging nature of nitride synthesis. Here, we demonstrate a facile self-combustion synthesis route to novel ternary molybdenum nitrides. The room temperature mixing of NaNH2, MoCl4, and 3d transition metal chlorides, such as MnCl2, FeCl2, and CoCl2, initiates a highly exothermic metathesis reaction, which is thermodynamically driven by the formation of stable NaCl, N2, and NH3 byproducts. The rapid combustion reaction yields ternary rocksalt γ-TMxMo1-xN0.5 nanoparticles (TM = Mn, Fe, Co) in just a few seconds. We calculate from DFT that these disordered ternary molybdenum nitrides are thermodynamically stable under the high-temperatures at which they form but are remnantly metastable when quenched to ambient conditions. Introduction of Mn, Fe, and Co into γ-Mo2N is found to change its magnetic properties and to enhance its oxygen reduction catalytic activities. Our work demonstrates self-combustion synthesis as a simple but powerful route for the realization of novel ternary intermetallic nitrides with emergent functionality.

Plastids are pivotal target organelles for comprehensively enhancing photosynthetic and metabolic traits in plants via plastid engineering. Plastidial proteins predominantly originate in the nucleus and must traverse membrane-bound multiprotein translocons to access these organelles. This import process is meticulously regulated by chloroplast-targeting peptides (cTPs). Whereas many cTPs have been employed to guide recombinantly expressed functional proteins to chloroplasts, there is a critical need for more efficient cTPs. Here, we performed a comprehensive exploration and comparative assessment of an advanced suite of cTPs exhibiting superior targeting capabilities. We employed a multifaceted approach encompassing computational prediction, in planta expression, fluorescence tracking, and in vitro chloroplast import studies to identify and analyze 88 cTPs associated with Arabidopsis thaliana mutants with phenotypes linked to chloroplast function. These polypeptides exhibited distinct abilities to transport green fluorescent protein (GFP) to various compartments within leaf cells, particularly chloroplasts. A highly efficient cTP derived from Arabidopsis plastid ribosomal protein L35 (At2g24090) displayed remarkable effectiveness in chloroplast localization. This cTP facilitated the activities of chloroplast-targeted RNA-processing proteins and metabolic enzymes within plastids. This cTP could serve as an ideal transit peptide for precisely targeting biomolecules to plastids, leading to advancements in plastid engineering. Plastids are important organelles that can be engineered to enhance photosynthetic and metabolic traits in plants. This study identifies a chloroplast-targeting peptide that is highly efficient in delivering biologically functional proteins to plastids in plants. [ABSTRACT FROM AUTHOR]

In plant engineering, plastid transformation is more advantageous than nuclear transformation because it results in high levels of protein expression from multiple genome copies per cell and is unaffected by gene silencing. The common plastid transformation methods are biolistic bombardment that requires special instruments and PEG-mediated transformation that is only applicable to protoplast cells. Here, we aimed to establish a new plastid transformation method in tobacco, rice, and kenaf using a biocompatible fusion peptide as a carrier to deliver DNA into plastids. We used a fusion peptide, KH-AtOEP34, comprising a polycationic DNA-binding peptide (KH) and a plastid-targeting peptide (AtOEP34) to successfully deliver and integrate construct DNA into plastid DNA (ptDNA) via homologous recombination. We obtained transformants in each species using selection with spectinomycin/streptomycin and the corresponding resistance gene aadA. The constructs remained in ptDNA for several months after introduction even under non-selective condition. The transformants normally flowered and are fertile in most cases. The offspring of the transformants (the T1 generation) retained the integrated construct DNA in their ptDNA, as indicated by PCR and DNA blotting, and expressed GFP in plastids from the integrated construct DNA. In summary, we successfully used the fusion peptide method for integration of foreign DNA in tobacco, rice, and kenaf ptDNA, and the integrated DNA was transmitted to the next generations. Whereas optimization is necessary to obtain homoplasmic plastid transformants that enable stable heterologous expression of genes, the plastid transformation method shown here is a novel nanomaterial-based approach distinct from the conventional methods, and we propose that this easy method could be used to target a wide variety of plants.

The chloroplast NDH complex interacts with Photosystem I to form the NDH-PSI supercomplex. Here the authors show that Arabidopsis NDF5 shares a common ancestor with the NDH subunit PnsB2 and acts as an NDH assembly factor initiating the assembly of PnsB2 and the evolutionarily distinct PnsB3.

Masaki Odahara and Kensuke Nakamura et al. use deep paired-end sequencing to examine organellar genome recombination when homologous recombination repair genes are individually knocked out in the moss, Physcomitrella patens. Their results suggest that chloroplasts and mitochondria share a common mechanism for replication-related rearrangements.

Each plant cell has hundreds of copies of the chloroplast genome and chloroplast transgenes do not undergo silencing. Therefore, chloroplast transformation has many powerful potential agricultural and industrial applications. We previously succeeded in integrating exogenous genes into the chloroplast genome using peptide–DNA complexes composed of plasmid DNA and a fusion peptide consisting of a cell-penetrating peptide (CPP) and a chloroplast transit peptide (cpPD complex). However, how cpPD complexes are transported into the chloroplast from outside the cell remains unclear. Here, to characterize the route by which these cpPD complexes move into chloroplasts, we tracked their movement from the extracellular space to the chloroplast stroma using a fluorescent label and confocal laser scanning microscopy (CLSM). Upon infiltration of cpPD complexes into the extracellular space of Arabidopsis thaliana leaves, the complexes reached the chloroplast surface within 6h. The cpPD complexes reached were engulfed by the chloroplast outer envelope membrane and gradually integrated into the chloroplast. We detected several cpPD complexes localized around chloroplast nucleoids and observed the release of DNA from the cpPD. Our results thus define the route taken by the cpPD complexes for gene delivery from the extracellular space to the chloroplast stroma.

The change of the shell structure in atomic nuclei, so-called “nuclear shell evolution”, occurs due to changes of major configurations through particle-hole excitations inside one nucleus, as well as due to variation of the number of constituent protons or neutrons. We have investigated how the shell evolution affects Gamow-Teller (GT) transitions that dominate the β decay in the region below 132Sn using the newly obtained experimental data on a long-lived isomer in 127Ag. The T1/2=67.5(9) ms isomer has been identified with a spin and parity of (27/2+) at an excitation energy of 1942−20+14 keV, and found to decay via an internal transition of an E3 character, which competes with the dominant β-decay branches towards the high-spin states in 127Cd. The underlying mechanism of a strong GT transition from the 127Ag isomer is discussed in terms of configuration-dependent optimization of the effective single-particle energies in the framework of a shell-model approach.

The neutron-rich isotopes of palladium have attracted considerable interest in terms of the evolution of the N=82 neutron shell closure and its influence on the r-process nucleosynthesis. In this Letter, we present the first spectroscopic information on the excited states in 125Pd79 and 127Pd81 studied using the EURICA γ-ray spectrometer, following production via in-flight fission of a high-intensity 238U beam at the RIBF facility. New isomeric states with half-lives of 144(4) ns and 39(6) μs have been assigned spins and parities of (23/2+) and (19/2+) in 125Pd and 127Pd, respectively. The observed level properties are compared to a shell-model calculation, suggesting the competition between proton excitations and neutron excitations in the proton-hole and neutron-hole systems in the vicinity of the doubly magic nucleus 132Sn.

Salt/polyethylene glycol (PEG) mixtures are employed as precipitants for biological macromolecules. The dependence of precipitation curves (PCs) on salt species was investigated for integral membrane protein/detergent particles. By relating this dependence to properties of ions dissociated from added salts, the following roles and effects of various ions were clarified. In the presence of ions whose interaction with water is stronger than water–water interaction, the coordination of solvent molecules is rearranged so as to strengthen short-range steric repulsion and hydrophobic attraction. Ions whose interaction with water is weaker than water–water interaction can be a hindrance to hydrophobic–hydrophobic contact. Moreover, strong electric fields of divalent cations can cause an attractive effect between electronegative or polar groups of neighboring particles. The variations of particle–particle and particle–PEG interactions depending on the state of particles and surrounding solvents were correlative. Due to this, the relationship between the horizontal positions of PC and the species of salts added could be formulated as a binary linear function of cationic and anionic species composing the salts.

The neutron-rich dysprosium isotopes 168Dy102 and 169Dy103 have been investigated using the EURICA γ-ray spectrometer, following production via in-flight fission of a high-intensity uranium beam in conjunction with isotope separation through the BigRIPS separator at RIBF in RIKEN Nishina Center. For 168Dy, a previously unreported isomer with a half-life of 0.57(7) μs has been identified at an excitation energy of 1378 keV, and its presence affirmed independently using γ-γ-γ coincidence data taken with Gammasphere via two-proton transfer from an enriched 170Er target performed at Argonne National Laboratory. This isomer is assigned Jπ=Kπ=(4−) based on the measured transition strengths, decay patterns, and the energy systematics for two-quasiparticle states in N=102 isotones. The underlying mechanism of two-quasiparticle excitations in the doubly midshell region is discussed in comparison with the deformed QRPA and multi-quasiparticle calculations. In 169Dy, the B(E2) value for the transition de-exciting the previously unreported Kπ=(1/2−) isomeric state at 166 keV to the Kπ=(5/2−) ground state is approximately two orders of magnitude larger than the E2 strength for the corresponding isomeric-decay transition in the N=103 isotone 173Yb, suggesting the presence of a significant γ-vibrational admixture with a dominant neutron one-quasiparticle component in the isomeric state.