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The number of individuals in a given space influences animal interactions and network dynamics. Here the authors identify general rules underlying density dependence in animal networks and reveal some fundamental differences between spatial and social dynamics.

Proteins in the fungal plasma membrane are key antifungal targets but their native structure and spatial distribution are poorly understood. Here, Jiang et al. use proteomics and cryo-electron tomography to investigate the organisation of membrane proteins in the fungal plasma membrane and how this is affected by antifungal drugs.

Natural variation in hecw-1 encoding an E3 ubiquitin ligase influences the avoidance of pathogenic bacteria by Caenorhabditis elegans and forms a molecular basis for behavioural variation.

The arcuate fascicle connection with the middle temporal gyrus has been considered unique to humans. Using high-resolution diffusion MRI, the authors systematically show this connection in chimpanzees, suggesting a gradual evolution of the language network.

RMC-7977, a compound that exhibits potent inhibition of the active states of mutant and wild-type KRAS, NRAS and HRAS variants has a strong anti-tumour effect on RAS-addicted tumours and is well tolerated in preclinical models.

Wild foods may contribute to food security through different pathways. Using a monthly interval dataset from two rural districts in India, this study elucidates the impact of wild food consumption from forests and common lands on women’s dietary diversity.

Free energy calculations are an essential tool to identify targets for individual proteins. Here, authors describe free energy perturbation (FEP+) calculations to optimise on target and off-target potencies for the discovery of potent Wee1 inhibitors with kinome-wide selectivity.

Patients who express a hyperactive mutant of the kinase PI3K exhibit defective humoral immunity. Preite et al. show that overactive PI3K leads to defective class-switched antigen-specific responses to immunization, despite augmented germinal-center formation and reactivity to commensal microbes and self antigens.

In this study, Kabonick et. al. reveal how high sugar diets disrupt Bacteroides intestinal fitness via a glycolytic pathway that is hierarchically governed to rapidly alter transcription by controlling the global transcription factor, Cur, functionally mimicking carbon catabolite repression. The intimate connection between the catabolism of dietary sugars and dramatic alterations to the Bacteroides transcriptome coordinates the prioritization of intestinal nutrients, a process that is necessary for gut fitness.

Small proteins (<50 kDa) are difficult to resolve by cryo-EM due to low signal-to-noise ratios and alignment challenges. Here, authors engineered conformationally rigid antibody fragments (Rigid Fabs) enabling high-resolution cryo-EM structures of small (~20 kDa) proteins like KRAS.

The authors identify defective viral particles, in people with non-suppressible HIV-1, that can replicate through superinfection and interfere with the wild-type virus. However, they show no evidence of these preventing disease progression in the individuals studied.

In this study, the authors present antimalarial drug resistance surveillance data from Uganda over the period 2019-2024. They measure ex vivo susceptibility to nine standard antimalarials in 1,114 isolates and characterise sequences of markers of drug susceptibility.

Transthyretin amyloid cardiomyopathy is a treatable but often unrecognized cause of heart failure. We derived and validated a machine learning model based on medical diagnostic codes that identifies heart failure patients at risk for wild-type transthyretin amyloid cardiomyopathy.

Consuming microplastics is known to harm marine wildlife in several ways, but effects on the microbiome are understudied. Here the authors demonstrate that two species of wild seabirds with larger amounts of microplastic in their guts had fewer commensal gut microbial species but more pathogens.

A study using Arabidopsis shows that plants can monitor the integrity of their outer barriers by sensing gas diffusion, enabling them to initiate wound repair to prevent water loss and pathogen entry.

The authors in this work identify an in vivo CNS active bifunctional degrader of GSK3. This was discovered via development of orthogonally reactive linker chemistry and a direct-to-biology screen that was able to provide hits of in vivo chemical probe quality.

Inactivating PPP2R1A mutations correlate with better survival after immune checkpoint blockade in patients with ovarian clear cell carcinoma, suggesting that targeting the phosphatase 2A (PP2A) pathway may represent an effective startegy for improving responses to immunotherapy.

High-content protein arrays were used to identify cysteine dioxygenase (CDO1) as a small-molecule glue target for the von Hippel–Lindau (VHL) E3 ubiquitin ligase and induces VHL-dependent proteasomal degradation of CDO1 in cells.

Sweetpotato is an important food security crop providing rich source of macro- and micronutrients including carbohydrates and vitamins. Here, the authors assemble of the two diploid relatives of cultivated sweetpotato and identify genes and alleles associated with carotenoid biosynthesis from breeding lines.

PUF proteins, conserved stem cell regulators, maintain germline stem cells with partner proteins in nematodes. Here, authors discover a complex of two FBF-2 PUF proteins and partner LST-1 that represses target mRNA via adjacent regulatory elements.

Available wheat genomes are annotated by projecting Chinese Spring gene models across the new assemblies. Here, the authors generate de novo gene annotations for the 9 wheat genomes, identify core and dispensable transcriptome, and reveal conservation and divergence of gene expression balance across homoeologous subgenomes.

Panoptes, an anti-phage defence system against virus-mediated immune suppression, is revealed.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Here, the authors link early immune cell hypoxia signatures to typhoid disease development in humans and, using mouse models, show that this immune response is triggered by Salmonella gut invasion, implicating a causal role in typhoid fever pathogenesis.

This study shows that p300/CBP-dependent H2B acetylation is crucial for maintaining transcription of oncogenic gene programs in androgen receptor-driven prostate cancer.

The function of wild-type KRAS in KRAS mutant cancers remains to be explored. Here, the authors show that deletion of the tumour-suppressive wild-type Kras in a KRASG12D driven colon cancer model exacerbates tumour initiation in a MAPK dependent manner, while acting to suppress metastasis through impaired immune suppression.

Sphingolipid desaturases can modify membrane lipids and change cold tolerance. Two of these enzymes have the same function in Arabidopsis and moss, but their evolutionary origins are different.

Experimental deletion of the furin cleavage site of the SARS-CoV-2 spike protein highlights an important role for this site in infection and the need to consider this site when evaluating the neutralization activities of antibodies.

Responsive exocytosis in neutrophil leukocytes involves actin depolymerisation-dependent sequential release of gelatinase granules, then strongly pro-inflammatory azurophilic granules. Here authors show that the actin nucleator protein WASH facilitates the initial step of innate immune activation by gelatinase granules while inhibiting release of pro-inflammatory granules.

ADP-heptose binds to ALPK1, triggering transcriptional reprogramming and NF-κB activation, endowing pre-leukaemic cells with a competitive advantage due to excessive clonal proliferation.

Water plays an essential role in enzyme catalysis, but direct observations linking enzyme catalysis and active-site water pose a significant challenge due to experimental difficulties. Here, the authors employ an ultraviolet photolysis technique with temperature-controlled X-ray crystallography to track the catalytic pathway of carbonic anhydrase II at 1.2 Å resolution.

Clonal hematopoiesis is driven by the selective advantage of mutant hematopoietic stem cells. Here, authors discover that elevated mitochondrial activity is a targetable mechanism by which mutant hematopoietic stem cells gain a selective advantage.

Human enhancers contain a high density of sequence features that are required for their normal in vivo function.

Zhang, Lahry, Cipurko et al. show that the microbial metabolites queuine and preQ₁ modify the same host tRNA. PreQ₁-tRNA reduces cell proliferation, slows tumour growth, decreases the translation of ribosomal proteins and is cleaved by IRE1 on the ER ribosome.

Here, Isaacs, Nieto and Zhang et al. discover a potent nanobody and engineer a dual-action antibody that targets two viral proteins, offering strong protection against Nipah and Hendra viruses while preventing viral escape, potentially contributing to future treatments.

Light-oxygen-voltage (LOV) photoreceptors perceive blue light to elicit spatio-temporally defined cellular responses, and their signalling process has been extensively characterized. Here the authors report that the light signal is still transduced in the absence of a conserved Gln residue, thought to be key.

Dnmt3a mutations in mouse haematopoietic stem and progenitor cells equivalent to R882 mutations in human cause increased mitochondrial respiration, suggesting that this is a mechanism of clonal haematopoiesis and a potential therapeutic target.

Choby et al. show that dynamic increases in the copy number of preexisting β-lactamase genes in heteroresistance enables resistance of continua of cellular subpopulations, flexibly overcoming enhanced β-lactams without new evolution and threatening the β-lactam pipeline.

Dalit, Tan and colleagues provide a multiomic profile of T follicular helper (T_FH) cells responses to diverse pathogens, revealing a blueprint for transcriptional flexibility and new tools to interrogate T_FH heterogeneity in mice and humans.

The native anaplastic lymphoma kinase (ALK) oncofetal protein is expressed in neuroblastoma and in multiple pediatric and adult solid tumors. Here, the authors show an ALK-directed antibody-drug conjugate with therapeutic efficacy in ALK-expressing preclinical models.