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Mycoplanecins show promising activity against tuberculosis. Here, the authors identify and study mycoplanecins’ biosynthesis, antibacterial effects, and binding mechanism to DnaN, suggesting potential for fighting multidrug-resistant tuberculosis.

The authors present a method for the conversion of full-length tau protein into seeding-competent amyloid fibrils without heparin or other negatively charged co-factors, which could be useful for studying the effects of post-translational modifications on Tau aggregation as well as to identify potential inhibitors of tau aggregation. Biochemical experiments and solid-state NMR spectroscopy measurements show that these co-factor-free tau fibrils have similar properties as amyloid fibrils isolated from brain tissue but differ from those of commonly used heparin-induced tau fibrils.

The SARS-CoV-2 viral genome is encapsulated by the nucleocapsid protein (N^SARS-CoV-2) that is essential for viral replication. Here, the authors show that RNA induces liquid-liquid phase separation of N^SARS-CoV-2 and how N^SARS-CoV-2 phosphorylation modulates RNA-binding and phase separation and that these RNA/N^SARS-CoV-2-droplets recruit and concentrate the SARS-CoV-2 RNA-dependent RNA polymerase complex in vitro, which would enable high initiation and elongation rates during viral transcription.

High-resolution imaging is essential for quantum simulation and computation in optical lattices and tweezers. Here, authors achieve fast 2.4-microsecond single-atom imaging with 99.4% fidelity and demonstrate number-resolved imaging without parity projection, advancing quantum readout capabilities.

Gut microbiota factors including IgA coating can predict disease severity in a mouse model of multiple sclerosis.

Epitope tags are widely used in various applications, but often lack versatility. Here, the authors introduce a small, alpha helical tag, which is recognized by a high affinity nanobody and can be used in a range of different applications, from protein purification to super-resolution imaging and in vivo detection of proteins.

Human and mouse cells expressing a redox-insensitive GAPDH mutant that otherwise retains its catalytic activity are shown to be unable to upregulate the oxidative pentose phosphate pathway in response to oxidative stress.

The human heart is composed of distinct regions and cell types, but relatively little is known about their specific protein composition. Here, the authors present a region- and cell type-specific proteomic map of the healthy human heart, revealing functional differences and potential cell type markers.

Accumulating evidence suggests that disruption of autophagy is associated with neurodegeneration. Here the authors show that Plekhg5 acts as a GEF for Rab26, a small GTPase that promotes the autophagy of synaptic vesicles in neurons; mice lacking Plekgh5 develop late-onset motoneuron degeneration.

VVD-133214, a clinical-stage, covalent allosteric inhibitor of the helicase WRN, was well tolerated in mice and led to robust tumour regression in multiple microsatellite-instability-high colorectal cancer cell lines and patient-derived xenograft models.

Chapeau et al. develop a nonallosteric inhibitor of the interaction between YAP and all four TEAD proteins. Treatment with the inhibitor, either as monotherapy or in combination with other treatment modalities, leads to induction of cell death in several in vivo cancer models.

Macrophage-specific genetic ablation of the EMT inducer ZEB1 reveals its pivotal role in intracellular cytokine trafficking, boosting cytotoxic T cell abundance and immune responses, thereby reducing tumor growth and metastatic colonization in mice.

Using microbiome data analysis and a self-establishing metabolically cooperating yeast community model, the authors show that the presence of auxotrophs in a microbial community increases metabolic interactions between cells and fosters antimicrobial drug tolerance.

Base editors are effective and safe for cholesterol reduction in non-human primates.

The authors show that the N-acetyltransferase PamZ acts as a self-resistance factor disabling the antibacterial paenilamicin that is produced by the honey bee larvae pathogen Paenibacillus larvae.

The intensity of UVA light, in addition to the photoperiod, is shown to determine seasonal change in the marine mass spawning annelid Platynereis dumerilii.

Sex differences in fasting glucose and insulin have been identified, but the genetic loci underlying these differences have not. Here, the authors perform a meta-analysis of genome-wide association studies to detect sex-specific and sex-dimorphic loci associated with fasting glucose and insulin.

Here, the authors identify interleukin-3 as a predictive marker for severity and outcome of SARS-CoV-2 infection in a multi-center, prospective study and find that patients with severe COVID-19 have reduced circulating plasmacytoid dendritic cell levels compared to non-severe COVID-19 patients.

A DNA-encoded chemical library based on regio- and stereoisomers of phenylalanine has been synthesized and used for affinity-based selections against multiple target proteins. This approach led to the isolation and validation of potent ligands capable of CAR T-cell activation and tumour targeting.

Zhou et al. investigate the molecular events that follow neoadjuvant treatment in PDAC patients, explore signatures of heterogeneous response and persister phenotypes, identify a CYP3A link to resistance and suggest that it is useful in predicting response.

Bioinformatic and chemoproteomic approaches resulted in the identification of a homolog of human dipeptidyl peptidase 4 in the gut bacterium Bacteroides thetaiotaomicron that regulates envelope integrity and community fitness.

The mycobacterial ABC transporter IrtAB functions as a siderophore importer despite exhibiting an exporter fold in its structure, and contains a siderophore interaction domain capable of siderophore reduction and iron release inside the cell.

Antimicrobial peptide LL37 can bind nucleic acids and potentiate their sensing by endosomal TLRs. Here the authors show that LL37 binds to RNA from neutrophil extracellular traps (NETs), which amplifies inflammation and production of more LL37 and NETs via TLR8/13, suggesting that LL37 contribution to psoriasis may be fueled by NET-associated RNA.

While the sharp emission lines of microlasers are advantageous for cell tagging, their relatively large size can impede cell migration and behavior. Here, Fikouras et al. develop nano-sized lasers that can readily tag and track various types of cells, including through narrow constrictions.

Infection with SARS-COV-2 can result in self-limited upper airway infection or progress to a more systemic inflammatory condition including pneumonic COVID-19. Here the authors utilise a multi-omics approach to interrogate the immune response of patients with self-limiting upper respiratory SARS-CoV-2 infection and reveal a temporal immune trajectory they associate with viral containment and restriction from pneumonic progressive disease.

Life- and healthspan of organisms can be modulated by dietary, genetic, or pharmacological interventions, which often affect metabolic pathways. Here the authors report that Grainyhead 1 is an evolutionarily conserved, drug-inducible transcription factor that promotes longevity in C. elegans, and thus a potential target for the development of geroprotective drugs.

The authors report here that talin and kindlin, the two key integrin binders and activators, are bridged by paxillin to induce microclustering of integrins to potently bind to multivalent extracellular ligand and trigger rapid cell attachment.

In biological systems, controlled molecular motion along a particular path is realized by protein motors that travel along microtubule filaments. Now, control of motion with light has been achieved in a synthetic supramolecular system, in which anionic porphyrin molecules move along the fibres of a bis-imidazolium gel upon irradiation.

Cytidine base editors delivered to the liver of mice with phenylketonuria via adeno-associated viruses or lipid nanoparticles do not lead to detectable off-target edits in the RNA and DNA of hepatocytes.

Tau forms aggregates in the brains of Alzheimer patients. Here, the authors identify conditions, where the microtubule-binding repeats of Tau undergo a phosphorylation-dependent liquid–liquid phase separation, leading to molecular crowding in the formed Tau liquid droplets and characterize them by NMR and other biophysical methods.

A chemical probe BI-9321 for the PWWP1 domain of NSD3 and its inactive analog were identified. BI-9321 binds to the methyl-lysine binding site, reduces the association of NSD3 with chromatin and inhibits proliferation of acute myeloid leukemia cells.

A negative allosteric modulator of the G-protein-coupled receptor β₂-adrenergic receptor binds to a membrane-facing surface adjacent to a molecular switch for receptor activation, and its binding disrupts a water-mediated polar network stabilizing an inactive switch conformation.

Cell lines in which Nup96 is endogenously tagged with mEGFP, SNAP-tag, HaloTag or mMaple serve as versatile reference samples, enabling 3D resolution calibration, assessment of labeling efficiency and precise molecular counting.

The transcription factor PU.1 is an essential regulator of the pro-fibrotic gene expression program in fibroblasts; PU.1 expression is upregulated in various fibrotic diseases, whereas inactivation of PU.1 induces regression of fibrosis in a number of organs.

The effects of chaperones on the aggregation of different tau variants are examined in a large-scale study. Among other findings, the work reveals that DnaJA2 can inhibit tau aggregation, a role that is supported by analysis of samples from human brains.

A programmable quantum simulator based on Rydberg atom arrays is used to study the collective dynamics of a quantum phase transition and observe the phenomenon of quantum coarsening.

The realization of dipolar quantum solids with an ultracold gas of magnetic atoms in an optical lattice ushers in quantum simulation of many-body systems with long-range anisotropic interactions.

The role of TRPV1 in the CNS is not fully understood. Here the authors show that TRPV1 is expressed specifically in somatostatin-positive OLM interneurons of the hippocampus, where it promotes excitatory innervation of these cells.

Chiea Chuen Khor, Tin Aung, Francesca Pasutto, Janey Wiggs and colleagues report a global genome-wide association study of exfoliation syndrome and a fine-mapping analysis of a previously identified disease-associated locus, LOXL1. They identify a rare protective variant in LOXL1 exclusive to the Japanese population and five new common variant susceptibility loci.

The synthesis of analogues of graphene by two different means provides insight into the origins of massless particles and paves the way for studies of materials with exotic topological properties. See Letters p.302 & p.306