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EGFR inhibitors are standard of care in patients with EGFR-mutant non-small cell lung cancer (NSCLC) but resistance often develops. Here the authors report that the evolution of EGFR inhibitor resistance in EGFR-mutant NSCLC results in a sensitivity to the compound, MCB-613, and investigate the underlying mechanism of action.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

Climate change is altering how plants balance carbon gain and water loss. This study maps global leaf-level water-use efficiency over the past two decades, showing it is highest in regions that are cold or dry, increasing worldwide, and strongly influenced by atmospheric dryness.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

The Atlantic Meridional Overturning Circulation (AMOC) is predicted to slow with climate change. Sea surface temperature data and climate model analysis show that since 1900 natural variability has been dominant in AMOC changes; anthropogenic forcing is not yet reliably detectable by this method.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

A population genomic analysis of 1,854 Listeria soil isolates collected across the contiguous United States identifies geographically prevalent phylogroups with increased pangenome openness and recombination, as a result of adaptation to variable environments.

Niche conservatism is a key assumption when planning non-native species management, but it is not always met. This study suggests that regional differences in niche conservatism are primarily transient and thus a matter of time.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

A prospective nationwide genomic screening pilot for ten genes in young adults in Australia detected pathogenic variants in 2% of the population, most of whom were ineligible for government-funded genomic testing.

Synovial sarcoma (SyS) is a cancer driven by a fusion oncoprotein, SS18::SSX, but the mechanism underlying the oncoprotein-mediated tumorigenesis remains unclear. Here, the authors employ transgenic mouse models and multi-omics to show how SS18:SSX modifies the activity and recruitment of BAF-family chromatin remodeling complexes to drive SyS tumorigenesis.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

A tension-modulated DNA origami-based nanosensor, compatible with bulk biochemical analysis in cell lysates, is used to assess the force-induced interaction of proteins involved in cellular mechanotransduction.

The [1,2]-Wittig rearrangement of allylic ethers is traditionally considered to proceed via formation and recombination of radical pairs. Now it has been shown that an alternative reaction cascade, involving initial enantioselective [2,3]-rearrangement followed by base-promoted anionic fragmentation–recombination that proceeds with high enantiospecificity, allows a catalytic enantioselective [1,2]-Wittig process.

Translation initiation and elongation factors can be targets for cancer treatment. Here, the authors show that inhibiting translation elongation through eIF5A impairs mitochondrial function, slowing the proliferation of tumour cells.

This Perspective considers the addition of ACKR1 genetic testing for identifying ACKR1/DARC-associated neutropenia in patients receiving clozapine, recommending eligibility criteria and testing strategies while estimating substantial cost savings for the UK healthcare system and enhancing equitable treatment access.

TCR-engineered T cells have shown limited efficacy in part due to the absence of co-stimulation leading to limited accumulation in solid tumors. The authors here show engineering the CD8β coreceptor with an intracellular CD28 domain enhances cytokine production, persistence, and tumor control in vivo independent of tumor-associated co-stimulatory ligand encounter.

Accurate projections of heating and cooling needs are vital for planning energy use and achieving the sustainable development goals. A global dataset now maps global heating and cooling degree days, finding future hotspots, rising cooling demand and early shifts in energy needs with major global impacts.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Graphics processing unit-accelerated MMseqs2 offers tremendous speedups for homology retrieval from metagenomic databases, query-centered multiple sequence alignment generation for structure prediction, and structural searches with Foldseek.

Pseudomonas aeruginosa survives extreme acidity by importing lysine through the LysP transporter to regulate acid-resistance genes. Here, authors reveal the cryo-EM structure of LysP and show how specific hydrogen bonds enable lysine recognition.

This study demonstrates that the extracellular matrix (ECM) of the developing brain stabilizes recently born synapses. The authors identify a microglial metalloprotease that digests the ECM to increase the plasticity of these newborn synapses.

The cellular origin of soft-tissue cancers, such as synovial sarcoma (SyS), is unknown. Here, expression of the oncoprotein, SS18::SSX, in fibroblasts was sufficient to produce human-like SyS tumours, thereby identifying a cell of origin for SyS.

There is a need for an easy-to-use clinical tool, that could predict favorable early PSA response and subsequently enhance early risk stratification, as well as guide treatment planning. Here, the authors show that based on patient data from four phase III randomized trials, Nadir androgen receptor pathway inhibitor (APRI)- Derived Integrative Response (NADIR) model predicts favorable early PSA response to ≤0.2 ng/mL by 6 months in metastatic hormone sensitive prostate cancer (mHSPC) patients initiating treatment with an APRI.

MCL1 is an anti-apoptotic protein associated with cancer and therapy resistance. Here, the authors show that MCL1 regulates mTORC1 signalling and metabolism, explaining MCL1-inhibition reported cardiotoxicity, which can be mitigated by dietary leucine supplementation.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

RNA-binding proteins (RBPs) considerably expand the information content of the genome and can determine the lifespan, localization and function of RNA, thereby controlling when, where and how much protein is produced. There is a growing body of evidence that links RBPs to specialized functions of immune cells and they can also mediate cell-autonomous immunity to foreign RNA and to misfolded self-RNAs. This Review examines how RBPs regulate the biogenesis and fate of mRNAs to mediate immune cell function and cell-autonomous immunity and their roles in immunodeficiency, autoimmunity and chronic inflammation.