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Our knowledge of non-linear genetic effects on complex traits remains limited, in part, due to the modest power to detect such effects. While kernel-based tests offer a versatile approach to test for non-linear relationships between sets of genetic variants and traits, current approaches cannot be applied to Biobank-scale datasets containing hundreds of thousands of individuals. We propose, FastKAST, a kernel-based approach that can test for non-linear effects of a set of variants on a quantitative trait. FastKAST provides calibrated hypothesis tests while enabling analysis of Biobank-scale datasets with hundreds of thousands of unrelated individuals from a homogeneous population. We apply FastKAST to 53 quantitative traits measured across ≈ 300 K unrelated white British individuals in the UK Biobank to detect sets of variants with non-linear effects at genome-wide significance.

Mendelian randomization (MR) has emerged as a powerful approach to leverage genetic instruments to infer causality between pairs of traits in observational studies. However, the results of such studies are susceptible to biases owing to weak instruments, as well as the confounding effects of population stratification and horizontal pleiotropy. Here, we show that family data can be leveraged to design MR tests that are provably robust to confounding from population stratification, assortative mating, and dynastic effects. We show in simulations that our approach, MR-Twin, is robust to confounding from population stratification and is not affected by weak instrument bias, whereas standard MR methods yield inflated false positive rates. We then conduct an exploratory analysis of MR-Twin and other MR methods applied to 121 trait pairs in the UK Biobank data set. Our results suggest that confounding from population stratification can lead to false positives for existing MR methods, whereas MR-Twin is immune to this type of confounding, and that MR-Twin can help assess whether traditional approaches may be inflated owing to confounding from population stratification.

Plant senescence, as a highly integrated developmental stage, involves functional degeneration and nutrient redistribution. NAM/ATAF1/CUC (NAC) transcription factors orchestrate various senescence-related signals and mediate the fine-tuning underlying plant senescence. Previous data revealed that knockout of either NtNAC028 or NtNAC080 leads to delayed leaf senescence in tobacco (Nicotiana tabacum), which implies that NtNAC028 and NtNAC080 play respective roles in the regulation of leaf senescence, although they share 91.87% identity with each other. However, the mechanism underlying NtNAC028- and NtNAC080-regulated leaf senescence remains obscure. Here, we determined that NtNAC028 and NtNAC080 activate a putative jasmonic acid (JA) biosynthetic gene, NtLOX3 , and enhance the JA level in vivo. We found that NtNAC028 and NtNAC080 interact with each other and themselves through their NA-terminal region. Remarkably, only the dimerization between NtNAC028 and NtNAC080 stimulated the transcriptional activation activity, but not the DNA binding activity of this heterodimer on NtLOX3. Metabolome analysis indicated that overexpression of either NtNAC028 or NtNAC080 augments both biosynthesis and degradation of nicotine in the senescent stages. Thus, we conclude that NtNAC028 cooperates with NtNAC080 and forms a heterodimer to enhance NtLOX3 expression and JA biosynthesis to trigger the onset of leaf senescence and impact secondary metabolism in tobacco. [ABSTRACT FROM AUTHOR]

The framework material Eu[Ag(CN)2]3·3H2O exhibits a negative linear compressibility (NLC) of −4.2(1) TPa−1 over the largest pressure range yet observed (0–8.2 GPa). High-pressure single-crystal X-ray diffraction data show that the rapid contraction of the Kagome silver layers under compression causes the wine-rack lattice to expand along the c-axis. The hydrogen bonds between the water molecules and the main frameworks constrain the structural deformation under pressure and eventually a weak NLC effect generated. Furthermore, we found that the pressure-induced emission intensity increases almost 800-fold at 4.0 GPa, followed by a gradual decrease and disappearance at 8.1 GPa. Under compression, high pressure significantly tunes the triplet level positions near the Eu3+ ions, and horizontal displacement between a quenching excited state and the excited levels of Eu3+ facilitates the energy transfer process to the 5D0 excited state and limits the nonradiative corssover at elevated pressures, thus increasing the emission intensity. In addition, we observe a gradual band gap reduction with increasing pressure, and the sample could not be returned to the initial state after the pressure was completely released. By controlling the structural flexibility, we observe a coupled NLC and pressure-induced strong enhancement of the emission properties of Eu[Ag(CN)2]3·3H2O, which provides a new route for the design of new optical devices with intriguing luminescence properties under extreme environments. [ABSTRACT FROM AUTHOR]

Conversion-alloying-type compounds offer many new possibilities as anode materials for Li-ion cells, but also show some drawbacks related to their intrinsic characteristics. To overcome those limitations, the consecutive steps of electrochemical processes occurring in the selected Zn2SnO4 inverse spinel are studied in detail i.e. by operando X-ray diffraction, ex situ X-ray absorption spectroscopy, and transmission electron microscopy. Decomposition of the spinel phase upon the 1st lithiation proceeds with the precipitation of Li2O and metallic particles, which further form LiZn and LixSn. A multicomponent matrix is created, which allows for reversible lithium storage. After dealloying upon the 1st delithiation, a Li6ZnO4/Li4ZnO3-type phase is formed in the conversion reaction, indicating reactivity between ZnO and Li2O. Initially, α-Sn is likely precipitated, which is transformed into β-Sn during the 2nd cycle, indicating aggregation. Understanding the electrochemical reaction mechanism allowed identifying essential issues, important for the practical application of the Zn2SnO4 anode: too high reaction voltage vs. Li+/Li with large hysteresis during the conversion reaction; metallic particle aggregation; large volume changes during deep (de-)alloying; mechanical problems on prolonged cycling. While the full-range capacity of the developed anodes reaches 920 mA h g−1 after 10 cycles at a current of 50 mA g−1 and over 460 mA h g−1 at 1000 mA g−1, their operation range has to be limited in order to overcome the listed problems. This can be achieved by the controlled electrochemical prelithiation of Zn2SnO4 anodes before assembling full-cells. For the first time, excellent cycling stability is reached for micrometer-sized solid-state-synthesized Zn2SnO4, working in full Li-ion cells. [ABSTRACT FROM AUTHOR]

Our knowledge of the contribution of genetic interactions ( epistasis ) to variation in human complex traits remains limited, partly due to the lack of efficient, powerful, and interpretable algorithms to detect interactions. Recently proposed approaches for set-based association tests show promise in improving the power to detect epistasis by examining the aggregated effects of multiple variants. Nevertheless, these methods either do not scale to large Biobank data sets or lack interpretability. We propose QuadKAST, a scalable algorithm focused on testing pairwise interaction effects ( quadratic effects ) within small to medium-sized sets of genetic variants (window size ≤100) on a trait and provide quantified interpretation of these effects. Comprehensive simulations show that QuadKAST is well-calibrated. Additionally, QuadKAST is highly sensitive in detecting loci with epistatic signals and accurate in its estimation of quadratic effects. We applied QuadKAST to 52 quantitative phenotypes measured in ≈300,000 unrelated white British individuals in the UK Biobank to test for quadratic effects within each of 9515 protein-coding genes. We detect 32 trait-gene pairs across 17 traits and 29 genes that demonstrate statistically significant signals of quadratic effects (accounting for the number of genes and traits tested). Across these trait-gene pairs, the proportion of trait variance explained by quadratic effects is comparable to additive effects, with five pairs having a ratio >1. Our method enables the detailed investigation of epistasis on a large scale, offering new insights into its role and importance., (© 2024 Fu et al.; Published by Cold Spring Harbor Laboratory Press.)

Very recently, a new superconductor with T c = 80 K has been reported in nickelate (La 3 Ni 2 O 7 ) at around 15-40 GPa conditions (Nature, 621, 493, 2023), which is the second type of unconventional superconductor, besides cuprates, with T c above liquid nitrogen temperature. However, the phase diagram plotted in this report was mostly based on the transport measurement under low-temperature and high-pressure conditions, and the assumed corresponding X-ray diffraction (XRD) results were carried out at room temperature. This encouraged us to carry out in situ high-pressure and low-temperature synchrotron XRD experiments to determine which phase is responsible for the high T c state. In addition to the phase transition from the orthorhombic Amam structure to the orthorhombic Fmmm structure, a tetragonal phase with the space group of I 4/ mmm was discovered when the sample was compressed to around 19 GPa at 40 K where the superconductivity takes place in La 3 Ni 2 O 7 . The calculations based on this tetragonal structure reveal that the electronic states that approached the Fermi energy were mainly dominated by the e g orbitals (3d z 2 and 3d x 2 - y 2 ) of Ni atoms, which are located in the oxygen octahedral crystal field. The correlation between T c and this structural evolution, especially Ni-O octahedra regularity and the in-plane Ni-O-Ni bonding angles, is analyzed. This work sheds new light to identify what is the most likely phase responsible for superconductivity in double-layered nickelate.