生命科学最新文献

Cadmium (Cd) toxicity threatens rice production and food safety. While ethylene-responsive transcription factors (ERFs) are involved in stress responses, their role in Cd detoxification in rice is unclear. This study identifies OsERF104 as a key positive regulator of Cd tolerance in rice. We demonstrate that OsERF104, induced by Cd stress in an H₂O₂-dependent manner, directly activates the expression of OsPDR5 and OsPDR20, two plasma membrane ABC transporters responsible for Cd efflux. Loss-of-function OsERF104 showed increased Cd sensitivity and accumulation, while complementation restored wild-type phenotypes. Transcriptomic analysis revealed that OsERF104 is essential for Cd-inducible expression of OsPDR5 and OsPDR20. OsERF104 directly binds to GCC-box elements in the promoters of OsPDR5 and OsPDR20, activating their transcription, as confirmed by ChIP-qPCR, EMSA, Y1H, and luciferase assays. Overexpression of OsPDR20 in the oserf104 mutant rescued the Cd-sensitive phenotype. Collectively, our findings uncover a novel OsERF104-OsPDR5/OsPDR20 module that curtails Cd accumulation and enhances Cd tolerance, representing a promising target for breeding low-Cd rice.

T cells must reliably discriminate between foreign-derived antigens that require an adaptive immune response and nonspecific self-antigens that do not. This discrimination is highly specific to the affinity of the bond between the ligand and T-cell receptors (TCRs), and highly sensitive to the concentration of ligand. We examined the features of T-cell-mediated immunity in the context of multivalent ligand-receptor interactions between clusters of TCRs with peptide major histocompatibility complex-coated nanoparticles (NPs). Using Monte Carlo simulations of NP-T-cell surface interactions, we compared the effect of TCR clustering on the dose-response curves of bound TCRs when various NP design parameters were altered. These simulations revealed a trade-off between sensitivity and specificity, mediated by TCR clustering and NP geometry. Large TCR clusters enhance sensitivity to both NP valence and NP concentration at the expense of antigen specificity. This loss of specificity arises from two key effects of TCR clustering on NP binding: (1) steric hindrance caused by TCR proximity and NP size, leading to early saturation of bound TCRs; and (2) increased the avidity of multivalent low-affinity NPs. The combination of saturated high-affinity binding and amplified low-affinity binding resulted in impaired affinity-based discrimination. Finally, we demonstrated how kinetic proofreading (KPR) mechanisms mediated by TCR phosphorylation were able to recover specificity in models of T-cell activation. Together, these results suggest that multivalent ligand-receptor interactions promote greater sensitivity at the expense of specificity, and provide mechanistic insights into early T-cell activation that can guide the design of NPs for therapeutic applications.

Light enhances protein translation, enabling young seedlings to rapidly and timely acquire photosynthetic capacities. Sequential phosphorylation of ribosomal protein S6 (RPS6) was implicated in the light-enhanced translation; however, the exact phosphorylation sites and the biological relevance of RPS6 multi-phosphorylation in seedling development remain elusive. Here, we report the identification and quantification of RPS6A residues that exhibit dynamic, differential phosphorylation in seedlings grown in darkness or during the initial exposure to light. Among six C-terminal sites, four serine residues, serine-229 (S229), S231, S237 and S240, serve as seed sites for light-regulated sequential phosphorylation. Combinatorial mutations of the C-terminal serines/threonine (S/T) to aspartic acids (phospho-mimic) or alanines (phospho-null) partially rescued the reduced hypocotyl elongation in etiolated rps6a seedlings. De-etiolating rps6a seedlings expressing phospho-mimic or phospho-null RPS6A showed decreased photosynthetic protein accumulation and reduced translation capacity. These findings indicate that fully tunable phosphorylation of RPS6A is essential for its complete function in hypocotyl elongation, translation efficiency, and photosynthetic capacities in both etiolated and de-etiolating seedlings. Our results demonstrate that the structural integrity of the C-terminal S/T residues is vital for establishing precise phosphorylation codes of RPS6A in light or dark conditions. Even a single substitution at these conserved residues can disrupt the light-regulated phosphorylation-dephosphorylation dynamics of RPS6A, thereby impairing its functions. This also explains the evolutionary conservation and importance of these C-terminal S/T residues to warrant young seedlings' capacities to adapt effectively to changing light environments in their natural habitats.

In arterial smooth muscle cells, Piezo1 channels are involved in the regulation of vascular tone and remodeling in various diseases. They are non-selective cation channels, the activation of which can lead to depolarization of the smooth muscle cell membrane, Ca²⁺ entry through voltage-gated channels and the development of contraction. This work tested the hypothesis that Piezo1 channels are involved in regulating the tone of smooth muscle cells in small cerebral arteries, and functional contribution of these channels may change in chronic carotid artery stenosis. Constricting clips were placed on both common carotid arteries in rats (reducing the volume velocity of blood flow by at least 70%). After 4 weeks, the middle cerebral artery (MCA) was isolated for wire myography (after endothelial removal) and quantitative PCR. The level of MCA basal tone was lower in the rats of the Stenosis group than in the control group; contractile responses to thromboxane A2 receptor agonist U46619 were not changed. Incubation with Dooku1 (Piezo1 blocker, 30 µM) led to decreases in basal tone level and contractile responses to U46619 in MCA of control rats but did not have such effects in MCA of the Stenosis group. The contents of Piezo1 and voltage-gated L-type Ca²⁺ channel (Ca_V1.2) mRNAs did not differ between the groups, whereas the mRNA content of voltage-gated Ca²⁺ channels of the T type (Ca_V3.1) was decreased in the MCA of the Stenosis group compared to the control. Thus, Piezo1 channels have a pro-contractile effect in the smooth muscle cells of rat cerebral arteries, and this effect decreases with chronic stenosis of carotid artery. The decrease in the pro-contractile effect of Piezo1 in the MCA of rats of the Stenosis group may be associated with the development of changes not at the level of the Piezo1 channels themselves, but at subsequent stages of signal transduction to the contractile apparatus of smooth muscle cells.

Vitamin E (tocochromanols), a vital lipid-soluble antioxidant, is often deficient in maize-based diets. Our objective was to identify potential genomic regions associated with tocochromanols variation and evaluate the potential of genomic predictions for its improvement. We assessed 1044 tropical maize inbreds from three panels across multiple environments, and genotyped them with high-density single-nucleotide polymorphisms. Across panels, we identified 50 causal loci, including 15 in a combined panel associated with three grain tocochromanol components. Associated loci showed strong positive allelic effects (1.12- to 2.72-fold increment due to favourable allele) for improving tocochromanol content. Notably, four loci were associated with α-tocotrienol, and three loci with α-tocopherol were found to be stable, and one pleiotropic locus influenced both. Underlying candidate genes are enriched in cellular, catalytic, biosynthetic and metabolic processes, with 14 involved in the tocochromanol biosynthesis pathway. Favourable haplotypes on chromosomes 5 and 7, notably increased α-tocopherol (6.12-16.19 µg/g) and γ-tocopherol (32.12-102.31 µg/g) levels, respectively. Genomic prediction models proved useful in predicting tocochromanols with moderate-to-high prediction accuracies (0.43-0.52), demonstrating their potential to develop elite, high-tocochromanol lines. Our results provided valuable insights into the genetic architecture of tocochromanols and support accelerating biofortification through genome-wide selection to improve vitamin E levels in tropical maize.

Leguminous crop rotation (LC) and conservation tillage (CT) are nature-based solutions to mitigate climate change. Previous studies have shown significant variations in crop productivity and soil organic carbon (SOC) under LC and CT, largely influenced by site-specific conditions. However, the mechanisms driving the interactions between LC and CT to enhance compatibility across diverse environmental conditions remain unclear. This study conducted a meta-analysis combined with machine learning, using a high-resolution global database of 271 site experiments to evaluate the impact of LC, CT, and their interaction on crop yield and SOC, clarify the underlying mechanisms, and assess their global potential. Results indicated synergistic effects of LC and CT led to additional increases of up to 13.4% in yield and 8.6% in SOC. These benefits were more pronounced in warm-humid regions, with low initial soil fertility, fine soil texture, and low nitrogen (N) input. Among key factors influencing these interactive effects, N input and the initial soil carbon to nitrogen (C/N) ratio emerged as the top two determinants for crop yield and SOC changes. Globally, integrating LC and CT in farmlands could potentially increase crop production and SOC stock by 16.9% and 7.6%, respectively. Looking ahead, these practices could enhance crop production by up to 400 Tg (24.6%) and SOC stock by 8.4 Pg (10.0%), helping to address climate change under various future scenarios. These results highlight that optimising N input and the initial soil C/N ratio through LC-CT integration achieves a win-win scenario of increased crop yield and enhanced SOC sequestration, with significant potential under future climate conditions. This study provides a scientific basis for developing targeted farmland management strategies tailored to diverse environmental conditions worldwide.

Elucidating the mechanisms of drug resistance in acute myeloid leukemia (AML) cells is a critical endeavor in biomedicine and oncohematology. In our previous research utilizing permanent cell lines, we demonstrated that AML cells in three-dimensional multicellular cultures exhibited increased drug resistance. This study utilized flow cytometry and spectrofluorometry to demonstrate enhanced resistance of primary CD33+ AML cells, cultured in three-dimensional multicellular aggregates, to the cytotoxic effects of anthracyclines. This resistance was associated with the inhibition of the pro-apoptotic signaling pathway, a partial accumulation of cells in the G0/G1 phase of the cell cycle, and an elevation in the levels of the anti-apoptotic protein Bcl-2.