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Low oxidation state aluminium complexes have gained wide recognition as discrete and versatile 2-electron reductants, but neutral trimeric structures remain elusive. Here the authors report the synthesis and characterization of two neutral Al(I) trimers whose trimeric structure is retained in solution.

CDK4/6 inhibitors are promising treatments for ER+ breast cancer, however resistance remains a challenge. Here, the authors analyse the NeoPalANA cohort and indicate that a 33 gene signature was predictive of response to neoadjuvant anastrozole and palbociclib.

In social settings, people need to establish how much they contribute to shared outcomes. Here, the authors show that people strategically alter their actions to establish their level of control and identify neural activity underlying this process.

In the nucleus accumbens, acetylcholine boosts dopamine release to promote effortful behaviour.

Vibrio cholerae O1 outbreak strains are classified as Ogawa or Inaba serotypes, but the impact of serotype on pathogenicity is understudied. Here, the authors show that O1 antigen methylation in Ogawa strains promotes colonization and infectivity.

Access to green space has been a critical, and contentious, issue for neighbourhood inequality and health outcomes. This Analysis looks at how the COVID-19 pandemic interacts with availability of nature for urban residents.

Native state proteomics of PV interneurons revealed unique molecular features of high translational and metabolic activity, and enrichment of Alzheimer’s risk genes. Early amyloid pathology exerted unique effects on mitochondria, mTOR signaling and neurotransmission in PV neurons.

Conventional methods for human motion analysis using sensors tightly attached to the body are often uncomfortable. Here, the authors demonstrate motion recognition and prediction using sensors embedded in garments. The results provide guidance for the development of wearable technology integrated into everyday clothing.

Most active particles studied to date lack the ability to undergo controlled shape transformations and control over their propulsion in response to environmental stimuli. Here, the authors present a class of active particles made from stimuli-responsive materials that exhibit fully reversible shape-dependent propulsion.

CD44 expressed by fibroblastic reticular cells in secondary lymphoid organs regulates trafficking of dendritic cells, and thus has an essential role in the priming of T cells and the adaptive immune response.

Muscularis macrophages, housekeepers of enteric nervous system integrity and intestinal homeostasis, modulate α-synuclein pathology and neurodegeneration in models of Parkinson’s disease, and understanding the accompanying mechanisms could pave the way for early-stage biomarkers.

This study shows that non-invasive ultrasound to the human nucleus accumbens can modulate deep brain activity and enhance reward-guided learning, offering a potential alternative to invasive neuromodulation therapies.

The International Brain Laboratory presents a brain-wide electrophysiological map obtained from pooling data from 12 laboratories that performed the same standardized perceptual decision-making task in mice.

Here the authors present NCATS-SM0225, a small molecule that inhibits ERAD and selectively kills cancer cells by binding VDACs, disrupting calcium homeostasis, and triggering the PERK-STIM1 pathway to degrade ERAD regulators.

An in-depth analysis of tissue biopsies from patients with multiple myeloma and CAR T cell therapy-associated immune-related adverse events (CirAEs) after treatment with commercial BCMA-targeted CAR T cell therapy shows that CD4⁺ CAR T cells mediate off-tumor toxicities and that high CD4:CD8 ratio at apheresis, robust early CAR T cell expansion, ICANS and ciltacabtagene autoleuce treatment are independently associated with the development of CirAEs.

Radiation reaction (RR) on particles in strong fields is the subject of intense experimental research, but previous efforts lacked statistical significance due to the extreme regimes required. Here, the authors report a 5σ observation of RR and obtain strong, quantitative evidence favouring quantum models over classical, using an all-optical setup where electrons are accelerated by a laser in a gas jet before colliding with a second, intense pulse.

Geminin regulates DNA replication by binding CDT1 and preventing MCM helicase loading. Using a reconstituted system and structural modelling, the authors find geminin inhibits via steric clash with MCM, not by blocking the CDT1–MCM interface. Combined with CDK activity, it fully halts licensing.

Matthew L. Jockers, Matthew Sag and Jason Schultz explain why humanities scholars have pitched in to the Authors Guild v. Google lawsuit.

Rathmell and colleagues show that metabolic reprograming of regulatory T cells is associated with severity of critical illness in patients with and without sepsis.

Brain-wide recordings in mice reveal that prior expectations are distributed through recurrent loops across all levels of cortical and subcortical processing.

Here they demonstrate a therapeutic intervention elevating levels of CYP450-derived lipids to control the expansion of intermediate monocytes in tissue and peripheral blood, presenting a first in class therapeutic approach for treating chronic inflammatory disease.

DBiTplus represents an integrated experimental and computational workflow that unifies sequencing-based and imaging-based spatial omics, demonstrated by combining transcriptomic profiling and multiplexed protein imaging on the same tissue section.

Mitochondria that are transported from satellite glial cells in dorsal root ganglia to peripheral sensory neurons through tunneling nanotube-like structures provide protection against peripheral neuropathy.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

MK-7762 is a new oxazolidinone antitubercular agent that is structurally similar to linezolid, and demonstrated in vivo efficacy, lesion penetration and limited toxicity compared to linezolid, indicating it could be used in broad tuberculosis regimens.

The identification of cellular targets for natural products that potently inhibit the growth of cancer cell lines implicates oxysterol-binding proteins in the growth of cancer cells. These natural products, termed ORPphilins, also affect sphingomyelin biosynthesis.

A plasma lens capable of focusing broadband extreme-ultraviolet attosecond pulses is demonstrated.

How the complex interplay between multiple nutrients within the microenvironment dictates potential sites of metastatic cancer growth is explored.

Elevated levels of IL-33 induce the production of autoantibodies through an unknown mechanism. Here, the authors show that IL-33 disrupts splenic architecture and germinal center organization, causing an expansion of antibody-secreting plasmablasts and plasma cells. In multiple mouse models of inflammation, administration of IL-33 exacerbates the pathology, increasing the production of autoantibodies, whereas IL-33 blockade reverses autoantibody production in a model of lung inflammation.

Inversion of C3 stereochemistry of monoterpenoid indole alkaloids (MIAs) has to occur at some point during their biosynthesis; however, the mechanism has remained unresolved. Here, the authors report an oxidase–reductase enzyme pair encoded within a gene cluster and demonstrate their collaborative role in inverting MIA C3 stereochemistry.

CAR T cell therapies have been developed to treat paediatric diffuse intrinsic pontine glioma (DIPG), however, clinical efficacy remains limited. Here, the authors report that engineering B7-H3-targeting CAR T cells to express the chemokine receptor CXCR3-A enhances their trafficking and efficacy in DIPG preclinical models.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Controlled delivery of small molecule therapeutics is challenging. Here the authors report a simple and effective aptamer-based depot system where the formation of aptamer/drug complexes leads to sustained release, and using this approach demonstrate improved in vivo delivery of channel blockers.

This study explores the impact of mood and individual differences on trading off between possible rewards and checking for the presence for threat and escaping to safety in a gamified foraging task.

The endoplasmic-reticulum (ER) transmembrane protein IRE1 mitigates ER stress through kinase-ribonuclease and scaffolding activities. However, a significant nonenzymatic IRE1 dependency has been shown in cancer. Here, the authors design a proteolysis-targeting chimera (PROTAC) to fully disrupt cellular IRE1 protein, selectively blocking growth of IRE1-dependent cancer cells.

Accurately predicting the optimal pH level for enzyme activity is challenging due to the complex relationship between enzyme structure and function. Gado and colleagues show that a language model can effectively learn the structural and biophysical features to predict the optimal pH for enzyme activity.

De novo design of self-assembling protein nanostructures and materials is of significant interest, however design of complex, multi-component assemblies is challenging. Here, the authors present a stepwise hierarchical approach to build such assemblies using helical repeat and helical bundle proteins as building blocks, and provide an in-depth structural characterization of the resulting assemblies.

Methods enabling the synthesis of diverse collections of nature-inspired compounds with potential medicinal use are sought after in drug design. Here, the authors report a build/couple/pair strategy to efficiently construct chiral polycyclic scaffolds and show their diversification for drug discovery screening.

A combination of pyrimidine biosynthesis inhibitors and antiviral nucleoside analogues can boost the antiviral effect of nucleoside analogues against SARS-CoV-2.

The existing ENCODE registry of candidate human and mouse cis-regulatory elements is expanded with the addition of new ENCODE data, integrating new functional data as well as new cell and tissue types.

A combination of high-resolution spatial imaging, spatial proteomics and transcriptional data reveals sparse and heterogeneous bacterial signals in gliomas and brain metastases.

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.

Whether high-order frontal lobe areas receive raw speech input in parallel with early speech areas in the temporal lobe is unclear. Here, the authors show that frontal lobe areas get fast low-level speech information in parallel with temporal lobe speech areas.

Global regime on benefit-sharing for genetic resources should take account of non-commercial interests, says Matthew Cock.

Our brains constantly detect discrepancies between predicted and observed events to update our knowledge of the world. Here the authors identify a neural signal driving this cognitive update and an inhibitory circuit involved in computing the prediction mismatch.

How DNA Polymerase Epsilon accomplishes continuous leading strand synthesis during DNA replication is not understood. Here, the authors describe a two tiers mechanism required to sustain Pol Epsilon processivity: CHTF18-dependent loading of PCNA at leading strand and dsDNA binding by its POLE3-POLE4 subunits.

Particle fusion is a promising process for constructing nanomaterials, but challenging to control in synthetic systems. Here, the authors report a method for kinetically regulated particle fusion controlled by variation in polymer chain length.

Pulmonary type 2 inflammation is associated with type 2 innate lymphoid cells. Here the authors use the Collaborative Cross mouse panel to show that ILC2 abundance during type 2 lung inflammation is different across the panel and identify free-fatty acid receptor 3 (Ffar3) as a gene responsible and show cytokine and ILC2 functional changes.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

Emerging materials between molecules and materials demand new modeling approaches. Here, the authors present a localized active space approach that enables accurate and efficient band structure calculations to capture long-range charge and energy transfer in correlated materials.