Influenza A viruses (IAVs) pose a threat to human health. Although receptor specificity, polymerase adaptation, and airway tropism have been studied extensively, it remains unresolved how they combine to shape tropism in airway epithelia. Here, we show that avian IAVs infect ciliated and secretory cells but preferentially bind to ciliated cells because of higher apical alpha 2,3-linked sialic acid levels. As replication levels are comparable between cell types, this translates into overall preference for ciliated cells. Human IAVs also preferentially bind to ciliated cells despite comparable alpha 2,6-linked sialic acid abundance. Instead, they show higher viral RNA and protein levels in secretory cells, linked to their compatibility with human ANP32 proteins and modestly higher ANP32A/B expression in this cell type, resulting in equal infection levels across cell types. Our findings redefine IAV tropism in the human airway as a stage-resolved process shaped by the interplay between apical glycans, viral binding, polymerase cofactor compatibility, and cell-type-specific replication capacity, moving beyond receptor-centric models.
In simple microbial populations, the fitness effects of selected mutations are typically assumed to be constant, regardless of mutant frequency. This assumption underpins predictions about evolutionary dynamics, epistasis, and the maintenance of genetic diversity. Here, we systematically test this assumption using beneficial mutations from early generations of the Escherichia coli long-term evolution experiment (LTEE). Using flow cytometry-based competition assays, we find that frequency-dependent fitness effects are the norm rather than the exception, occurring in similar to 80% of strain pairs tested. Most competitions exhibit negative frequency dependence, where fitness advantages decline as mutant frequency increases. We demonstrate that the strength of frequency dependence is predictable from invasion fitness measurements, which explain approximately half of the biological variation in frequency-dependent slopes. We also observe violations of fitness transitivity in several strain combinations, indicating that competitive outcomes cannot always be predicted from fitness measured against a single reference strain. High-resolution measurements reveal that frequency dependence changes substantially within the growth cycle, with the net per-cycle effect reflecting the balance of opposing dynamics at different growth phases. Our results demonstrate that, even in a model system designed to minimize ecological complexity, subtle interactions between closely related genotypes create frequency-dependent selection that can fundamentally alter evolutionary trajectories.
Birefringent crystals are indispensable for optoelectronic applications, yet commercially available crystals still suffer from the drawback of insufficient birefringence. Meanwhile, tetracoordination units-traditionally confined to a tetrahedral geometry-have long been sidelined from mainstream high-performance birefringent materials due to their intrinsic nearly negligible polarizability anisotropy. Herein, we break this tetrahedral constraint-demonstrating tetracoordinate square-planar [ICl4] anions as a revolutionary platform for unprecedented birefringence. To achieve this, we report an improved synthesis method that avoids the use of toxic Cl2 gas, enabling the preparation of [C(NH2)3][ICl4] featuring square-planar [ICl4] units. This compound displays a birefringence of 0.975@550 nm, setting a new record that surpasses all existing compounds containing tetracoordinate structural units. The giant birefringence of this material is attributed to the strong polarization anisotropy induced by the unique square-planar geometry of the [ICl4] tetracoordinate units. This research provides theoretical guidance for designing high-performance polar materials based on tetracoordinate units in giant birefringent materials and promotes applications in related optoelectronic device.
Remote epitaxy of the corundum phase alpha-Ga2O3 is demonstrated through a domain-free, transfer-free monolayer of MoS2 template synthesized on sapphire. Despite the intrinsic nonidealities of MoS2-specifically its thickness and polar bonding characteristics-for remote epitaxy, single-crystalline alpha-Ga2O3 films are epitaxially grown on polycrystalline MoS2 with crystallographic fidelity comparable to those grown directly on bare sapphire. This observation substantiates that the substrate lattice potential can still be effectively transmitted through the MoS2 layer, facilitating epitaxial registry at the growth front. The resulting alpha-Ga2O3 films exhibit crystal quality and surface morphology on par with those grown directly on bare sapphire. Moreover, a centimeter-scale, crack-free alpha-Ga2O3 membrane was successfully exfoliated using a Ni stressor, underscoring the mechanical compatibility and scalability of the remote epitaxial process. Structural disordering observed with more-than-bilayer MoS2 further corroborates the remote epitaxy mechanism. First-principles calculations reveal that interfacial interactions between the bottom S atoms of MoS2 and the Al atoms of sapphire induce spatially modulated charge distributions on the MoS2 surface, creating energetically favorable adsorption sites for Ga species. Collectively, these findings establish a mechanistic framework for charge-mediated remote epitaxy across polar interfaces and expand the design space for heterogeneous integration of transferable wide bandgap Ga2O3 membranes in next-generation power electronics and optoelectronic devices.
In most cells, Malat1 long noncoding RNA localizes to the nucleus where it affects splicing and chromatin function. In mouse neurons, Malat1 is exported to the cytoplasm where it is translated to generate the M1 micropeptide. Here, we characterize an internal ribosome entry site (IRES) required for M1 translation that is sufficient to induce cap-independent expression of a downstream open reading frame. In vivo chemical probing and structural modeling defined a three-stem-loop RNA secondary structure that encompasses the active IRES segment and coincides with a mouse B1 SINE (short interspersed element) repetitive element. In affinity purification experiments, a minimal IRES/B1 RNA selectively bound ribosomal subunits, translation factors, and the known IRES cofactors Rack1 and hnRNP A2/B1. Depletion of Rack1 and hnRNP A2/B1 inhibited IRES-dependent translation of the reporter and expression of the endogenous M1 peptide. Our study identifies an unexpected functional unit hidden within a widely studied long noncoding RNA.
