Deep mutational scanning of influenza A virus NEP reveals pleiotropic mutations in its N-terminal domain.

The influenza A virus nuclear export protein (NEP) is a multifunctional protein that is essential for the viral life cycle and has very high sequence conservation. However, since the open reading frame of NEP largely overlaps with that of another influenza viral protein, non-structural protein 1, it is difficult to infer the functional constraints of NEP based on sequence conservation analysis. Besides, the N-terminal of NEP is structurally disordered, which further complicates the understanding of its function. Here, we systematically measured the replication fitness effects of >1,800 mutations of NEP. Our results show that the N-terminal domain has high mutational tolerance. Additional experiments demonstrate that N-terminal domain mutations pleiotropically affect viral transcription and replication dynamics, host cellular responses, and mammalian adaptation of avian influenza virus. Overall, our study not only advances the functional understanding of NEP, but also provides insights into its evolutionary constraints.

Epistasis mediates the evolution of the receptor binding mode in recent human H3N2 hemagglutinin.

The receptor-binding site of influenza A virus hemagglutinin partially overlaps with major antigenic sites and constantly evolves. In this study, we observe that mutations G186D and D190N in the hemagglutinin receptor-binding site have coevolved in two recent human H3N2 clades. X-ray crystallography results show that these mutations coordinately drive the evolution of the hemagglutinin receptor binding mode. Epistasis between G186D and D190N is further demonstrated by glycan binding and thermostability analyses. Immunization and neutralization experiments using mouse and human samples indicate that the evolution of receptor binding mode is accompanied by a change in antigenicity. Besides, combinatorial mutagenesis reveals that G186D and D190N, along with other natural mutations in recent H3N2 strains, alter the compatibility with a common egg-adaptive mutation in seasonal influenza vaccines. Overall, our findings elucidate the role of epistasis in shaping the recent evolution of human H3N2 hemagglutinin and substantiate the high evolvability of its receptor-binding mode.

An explainable language model for antibody specificity prediction using curated influenza hemagglutinin antibodies.

Despite decades of antibody research, it remains challenging to predict the specificity of an antibody solely based on its sequence. Two major obstacles are the lack of appropriate models and inaccessibility of datasets for model training. In this study, we curated a dataset of >5,000 influenza hemagglutinin (HA) antibodies by mining research publications and patents, which revealed many distinct sequence features between antibodies to HA head and stem domains. We then leveraged this dataset to develop a lightweight memory B cell language model (mBLM) for sequence-based antibody specificity prediction. Model explainability analysis showed that mBLM captured key sequence motifs of HA stem antibodies. Additionally, by applying mBLM to HA antibodies with unknown epitopes, we discovered and experimentally validated many HA stem antibodies. Overall, this study not only advances our molecular understanding of antibody response to influenza virus, but also provides an invaluable resource for applying deep learning to antibody research.

Literature review on antiobesity medication use for metabolic and bariatric surgery patients from the American Society for Metabolic and Bariatric Surgery Clinical Issues Committee.

The following literature search is in response to inquiries made to the American Society for Metabolic and Bariatric Surgery (ASMBS) regarding antiobesity medication (AOM) use in patients who are having or have already had metabolic and bariatric surgery (MBS). These recommendations are based on current clinical knowledge, expert opinion, and published peer-reviewed scientific evidence available at this time. This paper is not intended to establish a local, regional, or national standard of care. The paper will be revised in the future as additional evidence becomes available.

Effect of Solvent-Assisted Dispersions of Clay/Epoxy Nanocomposites on Steel Passivation.

Dispersion of clay in polymer matrices is important to improve their engineering performances. Here we report the effect of solvent on dispersion of montmorillonite (MMT) in an epoxy matrix by examining transmission electron micrographs and X-ray diffraction of MMT/epoxy composites prepared with solvents with different polarities. We found that N-metyl-2-pyrrolidone (NMP) used as a polar solvent exhibited the improved dispersion of MMT in the epoxy owing to positive interaction energies with components, which prevents the aggregation of MMT platelets. The solvent-assisted dispersion of MMT significantly increased the corrosion resistance of MMT/epoxy nanocomposites pre-coated onto steel plates.

High-performance triisopropylsilylethynyl pentacene transistors via spin coating with a crystallization-assisting layer.

The effects of spin speed and an amorphous fluoropolymer (CYTOP)-patterned substrate on the crystalline structures and device performance of triisopropylsilylethynyl pentacene (TIPS-PEN) organic field-effect transistors (OFETs) were investigated. The crystallinity of the TIPS-PEN film was enhanced by decreasing the spin speed, because slow evaporation of the solvent provided a sufficient time for the formation of thermodynamically stable crystalline structures. In addition, the adoption of a CYTOP-patterned substrate induced the three-dimensional (3D) growth of the TIPS-PEN crystals, because the patterned substrate confined the TIPS-PEN molecules and allowed sufficient time for the self-organization of TIPS-PEN. TIPS-PEN OFETs fabricated at a spin speed of 300 rpm with a CYTOP-patterned substrate showed a field-effect mobility of 0.131 cm(2) V(-1) s(-1), which is a remarkable improvement over previous spin-coated TIPS-PEN OFETs.

Effects of side-chain interdigitation on stability: an environmentally, electrically, and thermally stable semiconducting polymer.

A polymeric semiconductor, poly(3,6-dihexyl-[2,2']bi[thieno[3,2-b]thiophene]) (PDHTT), was synthesized and tested as an active layer in organic thin film transistors (OTFTs). This semiconductor showed considerable potential for use in commercial electronic devices because of its superior characteristics, particularly its good stability. PDHTT-based OTFTs exhibited high stability in air, retaining their initial performance after exposure to 70% relative humidity for 50 days; they were also stable under repeated electrical stress and even after exposure to temperatures as high as 250 °C. We attribute the remarkable stability of PDHTT OTFTs to the relatively low highest occupied molecular orbital (5.1 eV) level of the polymer and its highly interdigitated structure in the thin film state.