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Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

The yeast Rad1–Rad10 complex has multiple roles in DNA damage repair. Here the authors uncover mutants that uncouple the roles in UV excision repair and non-NER functions.

Lewis Cantley and colleagues report an integrated metabolic and transcriptomic study of non–small cell lung cancer (NSCLC) cell lines. They show that the activity of the serine/glycine biosynthetic pathway in NSCLC is highly heterogeneous and is regulated by NRF2 and that elevated expression of genes in this pathway confers poor prognosis in human NSCLC.

Telomerase-negative cells maintain their telomeres through an alternative pathway that involves DNA recombination after replication. In this pathway, the recombination endonuclease MUS81 is found to regulate telomeric recombination and maintains the length of telomeres by interacting with the telomere binding protein TRF2.

Prostate cancer is refractory to anti-CTLA-4 therapy, but the reason why is unclear. Padmanee Sharma and colleagues report that the inhibitory molecule VISTA, which negatively regulates T cells, is upregulated on macrophages in prostate tumors that have been treated with anti-CTLA-4 and may play a role in resistance to this immunotherapy.

Understanding how simple chemical mixtures transition into truly emergent systems is essential to create new lifelike materials. Here, the authors show a self-replicating system that can be maintained out-of-equilibrium by an oxidant fuel in analogy to simple metabolic cycles.

The surface area of neurons increases rapidly during neurite extension. Galli and colleagues show that the endoplasmic reticulum (ER)-resident SNARE protein Sec22b bridges the ER and plasma membrane during this process and contributes to plasma membrane expansion, but does not promote membrane fusion.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

A new method to quantify three masting components from individual tree-years has revealed that globally, masting is uncommon in tree species that depend on mutualist dispersers, with its distribution further mediated by climate and nutrient availability.

Establishment of the outer blood-retina barrier is a hallmark of retinal development but the contribution of choroid endothelial cells (ECs) is not known. Here the authors show in the developing mouse retina that ECs remodel the basement membrane and lead to enhanced barrier function of retinal epithelial cells.

The relationships that control seed production in trees are key to understand evolutionary pressures that have shaped forests. A global synthesis of fecundity data reveals that while seed production is not constrained by a strict size-number trade-off, it is influenced by taxonomy and nutrient allocation.

A collection of 1,406 high-quality, immunoprecipitation- and immunoblotting-grade monoclonal antibodies to 737 human transcription factors is made available as a community resource, along with all validation data.

A modelling analysis shows that an unusually long gamma-ray burst gave rise to a lanthanide-rich kilonova following the merger of a neutron star–neutron star or of a neutron star–black hole.

Pineda-Pardo et al. show that focal application of a strong permanent magnet over the supplementary motor area shifts the speed-accuracy tradeoff towards accuracy by modulating both cortical circuits and distant cortical networks. This study suggests the utility of transcranial static magnetic field stimulation for cognitive research.

Kumar et al. show that the lncRNA Malat1 prevents gasdermin D-mediated pyroptosis induction, in turn suppressing inflammatory cell death and mediating immune evasion and metastasis.

Early stellarator designs suffered from high particle losses, an issue that can be addressed by optimization of the coils. Here the authors measure the magnetic field lines in the Wendelstein 7-X stellarator, confirming that the complicated design of the superconducting coils has been realized successfully.

The Blursday database contains repeated measures of subjective time and related processes collected during the COVID-19 pandemic. The more isolated individuals felt, the slower time seemed to pass.

Time-dependent parameters in whole-brain models capture DMT’s transient effects, revealing heightened reactivity in fronto-parietal and visual regions induced by perturbations.

Characterizing the performance of small thermal machines beyond their mean values is a key challenge in the thermodynamics of small systems, where fluctuations often dominate. This work extends Carnot’s result for reversible cycles to arbitrary-order moments of work and heat fluctuations, providing universal bounds in the quasistatic regime.”

STIM proteins sense Ca²⁺ depletion in the ER and activate store-operated Ca²⁺ entry in response, a process associated with dendritic cell (DC) functions. Here, the authors show that optimal antigen cross-presentation in DCs requires the association of the chaperone molecule UNC93B1 with STIM1.

Tumour vasculature influences drug delivery. Here, the authors show that SOD3 re-expression enhances doxorubicin delivery and effects through normalization of tumour vasculature via the HIF-2a/VE-cadherin pathway.

Romero et al. show that the autophagy regulator TP53INP2 represses adipogenesis by promoting GSK3β sequestration and activation of β-catenin through an autophagy-dependent and ESCRT-dependent mechanism.

Bass et al. and Haahr et al. now identify ETAA1 as a critical replication stress response factor that interacts with DNA damage response proteins and activates ATR to maintain genomic stability.

Yofe et al. demonstrate that FcγR engagement early after anti-CTLA-4 blockade induces a rapid remodeling of innate immunity and activation of type I interferon signaling, which are crucial for successful anti-CTLA-4 therapy.

The lineage-specific receptor CSF1R controls macrophage development and homeostasis. Here the authors show that deletion of a conserved Csf1r enhancer (FIRE) selectively depletes brain microglia and resident macrophages in the epidermis, kidney, heart and peritoneum of otherwise healthy mice.

In vivo neural activity recordings in mice reveal that large-scale coupling of the prefrontal cortex with the hippocampus and parietal cortex is modulated by task requirements and navigation strategy during spatial learning.