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Appel et al. found that deceptive networks reached over 37 million Facebook and 3 million Instagram users during the 2020 US elections, with the majority of this exposure driven by 3 networks and amplified by ordinary users resharing the content.

Long-range interactions are challenging for machine learning interatomic potentials (MLIPs). Here, authors show that, by just learning from energies and forces, MLIPs can accurately capture electrostatics and predict atomic charges.

Dietary n-6 PUFAs enhance adipose tissue expandability through the PPARγ–LPCAT3 membrane remodelling axis.

Using activity-based chemical probes, oncogenic IDH1-R132H but not the wild type was found to acquire a unique autopalmitoylation at C269. This mutant-specific modification is critical for the enzyme’s abnormal activity in cancer.

CaMKII is a key enzyme in brain, heart, and egg cells, regulated by calcium signals. Here, authors show that charged residues in the variable linker tune CaMKII activity, a mechanism that may underlie cell type–specific responses.

Dataset analysis or uncertainty quantification (UQ) in atomistic machine learning (ML) often rely on model-based heuristics. Here, the authors present a model-free, information theoretical approach to estimate errors, UQ, and outliers for ML-driven simulations.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

The hepatocyte growth factor receptor MET is a receptor tyrosine kinase involved in cellular processes such as proliferation, migration, and survival. Here the authors combine molecular dynamics simulations and smFRET in cells, to investigate the early stages of MET activation.

Water-vapor interfaces have been studied with many techniques, yet open questions persist about their electronic and molecular structure. Here, the authors demonstrate the application of soft x-ray second harmonic generation to study the water surface by leveraging attosecond pulses at the LCLS and a flat liquid sheet microjet, providing insights on the H-bond structure.

A dipolar-passivation strategy enables all-perovskite tandem solar cells with a power conversion efficiency of over 30%.

There is a lack of atomic level insight on the role of defects on carbon nanotubes' growth. Here, authors present a machine learning force field to drive near-microsecond simulations the entire growth process of this material, unveiling mechanisms of defect formation and healing.

How soluble misfolded proteins can bypass chaperones is unknown. Utilizing a meta-analysis, multi-scale modelling, and new experimental data it is found that this phenomena is common and arises from misfolded states that are native-like and long-lived due to protein self-entanglements.

Lipid nanoparticles (LNPs) are a versatile class of clinically approved drug delivery vehicles, particularly for nucleic acid cargoes, but they often suffer from instability issues. Here, the authors report that the room temperature stability of small interfering RNA LNPs formulated with unsaturated ionizable lipids can be improved by inclusion of mildly acidic, antioxidant-containing buffers.

KCNQ1 (Kv7.1) channels are critical for heart rhythm homeostasis. Here, the authors report the KCNQ1 structure in an intermediate state, revealing unique S1–S2 conformations that illuminate channel gating and may aid targeted drug development.

The SARS-CoV-2 3CL main protease (3CL M^pro) is a chymotrypsin-like protease that facilitates the production of non-structural proteins, which are essential for viral replication and is therefore of great interest as a drug target. Here, the authors present the 2.30 Å room temperature crystal structure of ligand-free 3CL M^pro and compare it with the earlier determined low-temperature ligand-free and inhibitor-bound crystal structures.

Omecamtiv mecarbil and Mavacamten are small molecules directly modulating the force produced by β-cardiac myosin. In this work, the authors describe how the modulators Omecamtiv mecarbil and Mavacamten can have opposite effects on cardiac myosin force production despite occupying the same pocket.

By examining three model pyroelectric materials with different bonding characters along the out-of-plane direction, it is shown that their pyroelectric coefficients increase rapidly when the thickness of free-standing sheets becomes small.

Cryo-EM structures of the full-length Junin virus and Machupo virus spike glycoprotein complexes stabilized in the prefusion conformation. Analyses reveal features that regulate glycoprotein pH-dependent membrane fusion activity.

Epichaperomes are chaperone assemblies that reorganize protein networks under stress. Here, authors reveal how HSP90 phosphorylation drives epichaperome formation, linking this process to cancer cell behaviors and pluripotent stem cell functions.

Vapour-deposited glasses show high stability compared to that of aged glasses, but a structural understanding remains elusive. Here, Reid et al. find that vapour deposited and liquid-cooled glasses show identical structures, suggesting these two classes of films lie on the same path to equilibrium.

Gasdermin-A3 pore formation propagates along diverse pathways. It begins with membrane attachment and oligomeric pre-assembly. Once inserted in the membrane, the oligomers re-assemble into various shapes and sizes, which open their lytic pores.

An integrated approach combing solution and solid-state NMR, molecular dynamics simulations and neutron reflectometry is applied to characterize dynamic membrane bound forms of ADP-ribosylation factor 1 (Arf1).

Here authors use calorimetry to quantify chemical short-range order (CSRO) experimentally, in good agreement with atomistic simulations. Synchrotron in-situ tensile testing showed no effect of varied CSRO levels on mechanical properties.

Prismatic dislocation loops (PDLs) form during the elastic-to-plastic transition of a dislocation-free volume under nanoindentation. Here the authors observe the initial plasticity and burst-like emission of PDLs in Au nanowires by in-situ transmission electron microscopy, elucidating fundamental aspects of the formation process.

Effective anti-PD-1 immunotherapy is associated with the presence of polyclonal CD8⁺ T cells in the tumour and blood specific for a limited number of immunodominant mutations, which are recurrently recognized over time.

Determining dynamic ensembles of biomolecules is still challenging. Here the authors present an approach for rapid RNA ensemble determination that combines RNA structure prediction tools and NMR residual dipolar coupling data and use it to determine atomistic ensemble models for a variety of RNAs.

P-type ATPases adopt different conformations during their transport cycle, including autophosphorylated forms. The structure of type IB P-type ATPase CopA is now solved in its E2P state. Comparison with a previous E2Pi structure indicates that dephosphorylation is not coupled to ion extrusion, in contrast to mechanisms in type IIA SERCA. The findings explain the effect of disease-related mutations in human Cu⁺ transporters.

Neural Networks are known to perform poorly outside of their training domain. Here the authors propose an inverse sampling strategy to train neural network potentials enabling to drive atomistic systems towards high-likelihood and high-uncertainty configurations without the need for molecular dynamics simulations.

A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.

Prostate cancer (PrCa) involves a large heritable genetic component. Here, the authors perform multivariate fine-mapping of known PrCa GWAS loci, identifying variants enriched for biological function, explaining more familial relative risk, and with potential application in clinical risk profiling.

Therapeutic modulation of the complement system has gained interest over the past two decades. Here, the authors provide molecular-level insight into the mode-of-action, target selectivity and species specificity of the compstatin family of complement inhibitors, which entered the clinic in 2021.

Roger Milne and colleagues conduct a genome-wide association study for estrogen receptor (ER)-negative breast cancer combined with BRCA1 mutation carriers in a large cohort. They identify ten new risk variants and find high genetic correlation between breast cancer risk for BRCA1 mutation carriers and risk of ER-negative breast cancer in the general population.

Bacterial hairs called pili become highly-conductive electric wires upon addition of both natural and synthetic amino acids conjugated with gold nanoparticles. Here the authors use computationally-guided ordering further increasing their conductivity, thus yielding genetically-programmable materials.

A transcriptome-wide association study identifies associations of genetically predicted gene expression with breast cancer risk. This analysis finds 48 candidate genes implicated in breast cancer susceptibility, including 14 at novel loci.

The model archaeon Sulfolobus acidocaldarius produces several protein filaments with specialised functions, including flagellum-like archaella, Aap pili, and adhesive threads. Here, the authors describe high-resolution structures and distinct glycosylation patterns for the three filaments, and present an integrated model of the filaments in the context of the S-layer.

Terminal bd oxidases endow bacterial pathogens with resistance to cellular stressors. The authors report the structure of E. coli bd-II type oxidase with the bound inhibitor aurachin D, providing a structural basis for the design of specifically binding antibiotics.

Here, Li et al. perform a genome-wide CRISPR screen to identify host dependency factors for influenza A virus infection and show that the host mRNA cap methyltransferase CMTR1 is important for viral cap snatching and that it affects expression of antiviral genes.

Crystallographic dislocation has proven harmful to the carrier dynamics in conventional semiconductors but it is unexplored in metal halide perovskites. Here Jiang et al. grow remote epitaxial perovskite films on graphene with density-controlled dislocations and confirm their negative impact.

Oestrogen negative breast cancer is associated with a poor prognosis. In this study, the authors perform a meta-analysis of 11 breast cancer genome-wide association studies and identify four new loci associated with oestrogen negative breast cancer risk. These findings may aid in stratifying patients in the clinic.

NLRP3 is a critical intracellular inflammasome sensor and an important clinical target against inflammation-driven human diseases. Here, the authors determined Cryo-EM structures of human NLRP3 in its closed and open states, elucidating the mechanism of NLRP3 inflammasome activation.

Over 170 susceptibility loci have been identified by genome-wide association studies in breast cancer. Here, the authors interrogated the role of risk-associated variants from non-breast tissue, and using expression quantitative trait loci, identify potential target genes of known breast cancer susceptibility variants, as well as 11 regions not previously known to be associated with breast cancer risk.

Calmodulin (CaM) regulates a variety of membrane channels in response to Ca2+, but the precise mechanisms are still unclear. Now a combination of single-particle EM, molecular dynamics simulations and functional assays is used to elucidate the structure of Ca2+–CaM bound to the full-length aquaporin AQP0, revealing a cytoplasmic gate that is closed upon CaM binding to control channel permeability in an allosteric manner.

Modification of the internal and external surface chemistry of microporous zeolite and metal–organic framework nanocrystals leads to a generalizable strategy to aqueous porous liquids and impart high gas-carrying capacities to liquid water.

In situstudies of deformation in metal nanowires have yielded interesting results. Here, the authors perform cyclic loading on gold nanowires and observe twinning and detwinning phenomena, respectively caused by tensile and compressive loading, and elucidate the underpinning mechanism by molecular dynamics simulations.