综合性期刊最新文献

Thylakoid-free cyanobacteria are thought to preserve ancestral traits of early-evolving organisms capable of oxygenic photosynthesis. However, and until recently, photosynthesis studies in thylakoid-free cyanobacteria were only possible in the model strain Gloeobacter violaceus, limiting our understanding of photosynthesis evolution. Here, we report the isolation, biochemical characterization, cryo-EM structure, and phylogenetic analysis of photosystem I (PSI) from a recently discovered thylakoid-free cyanobacterium, Anthocerotibacter panamensis, a distant relative of the genus Gloeobacter. We find that A. panamensis PSI exhibits a distinct carotenoid composition and has one conserved low-energy chlorophyll site, which was lost in G. violaceus. Furthermore, PSI in thylakoid-free cyanobacteria has changed at the sequence level to a degree comparable to that of other strains, yet its subunit composition and oligomeric form might be identical to that of the most recent common ancestor of cyanobacteria. This study therefore provides a glimpse into the ancient evolution of photosynthesis.

Voltage-gated Na_v1.5 channels are central to the generation and propagation of cardiac action potentials. Aberrations in their function are associated with a wide spectrum of cardiac diseases including arrhythmias and heart failure. Despite decades of progress in Na_v1.5 biology, the lack of structural insights into intracellular regions has hampered our understanding of its gating mechanisms. Here, we present two cryo-EM structures of human Na_v1.5 in open states, revealing sequential conformational changes in gating charges of the voltage-sensing domains (VSDs) and several intracellular regions. Despite the channel being in the open state, these structures show repositioning, but no dislodging of the IFM motif in the receptor site. Molecular dynamics analyses show our structures with CTD conduct Na⁺ ions. Notably, our structural findings highlight a dynamic C-terminal domain (CTD) and III-IV linker interaction, which regulates the conformation of VSDs and pore opening. Electrophysiological studies confirm that disrupting this interaction alters fast inactivation of Na_v1.5. Together, our structure-function studies establish a foundation for understanding the gating mechanisms of Na_v1.5 and the mechanisms underlying CTD-related channelopathies.

Large language models (LLMs) show emergent patterns that mimic human cognition. We explore whether they also mirror other, less deliberative human psychological processes. Drawing upon classical theories of cognitive consistency, two preregistered studies tested whether GPT-4o changed its attitudes toward Vladimir Putin in the direction of a positive or negative essay it wrote about the Russian leader. Indeed, GPT displayed patterns of attitude change mimicking cognitive dissonance effects in humans. Even more remarkably, the degree of change increased sharply when the LLM was offered an illusion of choice about which essay (positive or negative) to write, suggesting that GPT-4o manifests a functional analog of humanlike selfhood. The exact mechanisms by which the model mimics human attitude change and self-referential processing remain to be understood.

Many biological studies involve inferring the evolutionary history of a sample of individuals from a large population and interpreting the reconstructed tree. Such an ascertained tree typically represents only a small part of a comprehensive population tree and is distorted by survivorship and sampling biases. Inferring evolutionary parameters from ascertained trees requires modeling both the underlying population dynamics and the ascertainment process. A crucial component of this phylodynamic modeling involves tree simulation, which is used to benchmark probabilistic inference methods. To simulate an ascertained tree, one must first simulate the full population tree and then prune unobserved lineages. Consequently, the computational cost is determined not by the size of the final simulated tree, but by the size of the population tree in which it is embedded. In most biological scenarios, simulations of the entire population are prohibitively expensive due to computational demands placed on lineages without sampled descendants. Here, we address this challenge by proving that, for any partially ascertained process from a general multitype birth-death-mutation-sampling model, there exists an equivalent process with complete sampling and no death, a property which we leverage to develop a highly efficient algorithm for simulating trees. Our algorithm scales linearly with the size of the final simulated tree and is independent of the population size, enabling simulations from extremely large populations beyond the reach of current methods but essential for various biological applications. We anticipate that this massive speedup will significantly advance the development of novel inference methods that require extensive training data.

Gating in voltage-dependent ion channels is regulated by the transmembrane voltage. This form of regulation is enabled by voltage-sensing domains (VSDs) that respond to transmembrane voltage differences by changing their conformation and exerting force on the pore to open or close it. Here, we use cryogenic electron microscopy to study the neuronal K_v2.1 channel in lipid vesicles with and without a voltage difference across the membrane. Hyperpolarizing voltage differences displace the positively charged S4 helix in the voltage sensor by one helical turn (~5 Å). When this displacement occurs, the S4 helix changes its contact with the pore at two different interfaces. When these changes are observed in fewer than four voltage sensors, the pore remains open, but when they are observed in all four voltage sensors, the pore constricts. The constriction occurs because the S4 helix, as it displaces inward, squeezes the right-handed helical bundle of pore-lining S6 helices. A similar conformational change occurs upon hyperpolarization of the EAG1 channel but with two helical turns displaced instead of one. Therefore, while K_v2.1 and EAG1 are from distinct architectural classes of voltage-dependent ion channels, called domain-swapped and non-domain-swapped, the way the voltage sensors gate their pores is very similar.

Synthetic genetic circuits that harness programmable protein modules and artificial transcription factors (ATF) to devise event-triggerable cascaded pathways represent an essential class of tools for studying cell biology. Fine-tuning the general structural functionality of ATFs is important for constructing orthogonal and composable transcriptional regulators. Here, we report the design of a protease-responsive conformationally inhibited system (PRCIS). By intramolecularly linking the free DNA-binding domains of ATF to confined dimerized regions, the transcriptional binding is conformationally inactivated. The function of DNA binding is reinstated upon proteolytic cleavage of linkages, activating the downstream gene expressions. The versatility of PRCIS design is demonstrated through its adaptability to various ATFs and proteases, showcasing high activation ratios and specificity. Furthermore, the development of PRCIS-based triple-orthogonal protease-responsive and dual-orthogonal chemical-inducible platforms and Boolean logic operations are elaborated in this paper, providing a generalizable design for synthetic biology.

The direct conversion of methane into valuable unsaturated C₂ hydrocarbons (C₂H₂ and C₂H₄) attracts growing attention. Non-thermal plasma offers a promising approach for this process under mild conditions. However, the competing formation of C₂H₆ and excessive dehydrogenation limit the selectivity toward C₂H₂ and C₂H₄. Herein, we develop a promising shielded bifunctional nanoreactor with a hollow structure and mesoporous channels (Na₂WO₄-Mn₃O₄/m-SiO₂) that effectively limits CH₄ overactivation and promotes selective coupling to form C₂H₂ and C₂H₄ under plasma activation, achieving 39% CH₄ conversion with 42.3% C₂H₂ and C₂H₄ fraction. This nanoreactor features isolated Na₂WO₄ embedded within the channels and Mn₃O₄ confined in the cavity of the SiO₂ hollow nanospheres, enabling internal tandem catalysis at co-located active sites. Na₂WO₄ induces the conversion of diffused CH₄ and CH₃ into reactive intermediates (^*CH and ^*CH₂), which subsequently couple on the Mn₃O₄ surface to form C₂H₂ and C₂H₄. Furthermore, the mesoporous channels inhibit the plasma discharge within the nanoreactor, preventing deep dehydrogenation of CH_x species to solid carbon. This nanoreactor demonstrates a highly selective route for the nonoxidative conversion of methane to valuable C₂ hydrocarbons, offering a new paradigm for the rational design of catalysts for plasma-driven chemical processes.

Developing bioinspired all-ceramics with plastic phases is considered one of the most effective ways to simultaneously achieve enhanced strength and toughness in ceramic materials for high-temperature applications. Here we explore tough and strong bioinspired high-entropy all-ceramics with a contiguous network structure that are able to serve up to 1300 °C. Specifically, we develop the high-entropy all-ceramics, featuring a unique contiguous network distribution of the Cr₇C₃ plastic phase within the predominant high-entropy carbide (HEC) hard phase, through a high-entropy composition-engineering strategy. The resulting materials exhibit impressive fracture initiation toughness of 12.5 ± 1.5 MPa·m^1/2 and flexural strength of 613 ± 52 MPa at room temperature, as well as ~97% strength retention up to 1300 °C due to their good high-temperature stability, surpassing the performance of most other reported bioinspired ceramics. Further experimental and theoretical investigations demonstrate that the Cr₇C₃ phase can undergo plastic deformation by forming nanoscale shear bands with significant crystal defects, resulting in multiple toughening mechanisms involving crack-bridging of unfractured Cr₇C₃ ligaments and crack deflection in the HEC/Cr₇C₃ all-ceramics. This work successfully develops tough and strong bioinspired high-entropy all-ceramics capable of serving up to 1300 °C, offering an innovative strategy that facilitates further design of bioinspired ceramics applicable at higher temperatures.