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

How synaptic plasticity rules lead to diverse neural responses in a spiking neural network model remains poorly understood. Here, the authors show how a diversity of response types contributes to network function and task performance.

Plant traits drive ecosystem dynamics yet are challenging to map globally due to sparse measurements. Here, the authors combine crowdsourced biodiversity observations with Earth observation data to accurately map 31 plant traits at 1 km² resolution.

The neural mechanisms underlying the diversity of hippocampal replay dynamics remain unclear. Here, using computational modelling, the authors show that modulation of firing-rate adaptation accounts for distinct replay modes and their relationships to behavioral state and oscillatory activity.

The anterior cingulate cortex encodes affective pain behaviours modulated by opioids; targeting opioid-sensitive neurons through a new chemogenetic gene therapy replicates the analgesic effects of morphine, providing precise chronic pain relief without affecting sensory detection.

Cytosolic CHMP5 is known for its primary function in membrane remodelling. Here the authors report that nuclear CHMP5 promotes T cell acute lymphoblastic leukemia initiation and maintenance in part through regulating epigenetic and transcriptional events.

Thendral et al. describe a mitophagic programme that removes deleterious mtDNA during the oocyte-to-zygote transition in Caenorhabditis elegans, promoting mitochondrial health and offspring survival. Loss of this mitophagy leads to mutant mtDNA accumulation.

Here they combine in vivo imaging with proteomics to characterize a protein complex comprised of Ccdc78 and Ccdc33 that acts at the extreme distal tip of 9 + 2 motile cilia to control tip architecture, cilia length, and cilia beating.

The prelimbic region of the prefrontal cortex is involved in goal-directed action. Here the authors investigate the function of the prelimbic pathways projecting along the anterior posterior striatal axis in value based decision making in male mice.

How the feedforward information from the nose and feedback from the cortex interact in the olfactory bulb is not fully understood. Here, by imaging olfactory sensory neurons and cortical projections to the olfactory bulb, the authors show that sensory transformations contained within both streams.

The efficiency of protein transfer by extracellular vesicles (EVs) remains unclear. Here, authors show that EVs from cell protrusions deliver functional Rac1 and genome-editing enzymes more efficiently than well-studied endosome-derived EVs, highlighting their potential as delivery tools.

The STAR experiment at the Relativistic Heavy Ion Collider at Brookhaven National Laboratory demonstrates evidence of spin correlations in \(\Lambda \bar{\Lambda }\) hyperon pairs inherited from virtual spin-correlated strange quark–antiquark pairs during QCD confinement.

The visual callosal pathway reciprocally connects mammalian visual cortices and is proposed to facilitate activation of binocular neurons. Here, the authors show that this pathway facilitates responses in both monocular and binocular neurons but these responses are gated by the ipsilateral lateral geniculate nucleus.

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.

Reproduction in numerous marine organisms is timed to specific moon phases, but the mechanisms for sensing moon phases are incompletely understood. Here the authors report that an ancient, light-sensitive protein L-Cryptochrome in a marine bristle worm can discriminate between sun- and moonlight, enabling the animals to properly decode moon phases.

CaBLAM is a bioluminescent genetically encoded calcium indicator that delivers high-contrast signals as shown in cell culture, in the in vivo mouse brain and in zebrafish larvae.

Weaver and colleagues report that enrichment of the extracellular matrix with tenascin C promotes aggressiveness of IDH1-mutant glioblastoma by activating a HIF1α-controlled mechanosignalling feedback loop.

Zheng et al. show neural evidence for a functional role of phase precession in human episodic memory.

A lightweight three-photon miniature microscope allows imaging neuronal activity throughout the cortex in freely moving mice.

The authors investigated the neocortical representations that mediate sensory–motor transformations in active sensing behavior. Layer 5 of vibrissae cortex generates a diverse, distributed network representation via active dendritic integration.

Engineering of local Anopheles gambiae under containment enables the generation of a transgenic strain equipped with non-autonomous gene drive capabilities that robustly inhibits genetically diverse Plasmodium falciparum isolates obtained from naturally infected children.

Gain-of-function mutations in CTNNB1 (encoding for b-catenin) leading to deregulated Wnt/β-catenin signaling are frequently observed in patients with hepatocellular carcinoma (HCC). Here the authors show that inhibiting b-catenin with lipid nanoparticles encapsulating siRNA targeting CTNNB1 impairs tumor growth and promotes anti-tumor immunity in preclinical HCC models.

The active zone is a brain signaling hub critical for synaptic information transfer and the encoding of behaviors. The authors identify Blobby as an assembly factor required for proper active zone nanoscale protein architecture and memory formation.

The development of RECORD, a high-throughput, customizable system offers an alternative model for unveiling the behavioral strategies leveraged by rodents during naturalistic foraging-like decision-making.

The ALICE Collaboration provides details on the microscopic mechanism that ends up creating antideuteron in high-energy proton–proton collisions at the Large Hadron Collider.

Splicing dysfunction has been observed in Alzheimer’s disease but it remains unclear whether splicing defects have a causal role. Here the authors generate a mouse model with perturbed U1 snRNP activity, recapitulating RNA splicing defects, neuron hyperexcitability, neurodegeneration and synergy with the amyloid cascade when crossed with 5xFAD mice.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

DNA replication stress is a driver of genome instability. Here, the authors identify a role of the E3 ligase RNF25 in promoting replication stress tolerance. Mechanistically, RNF25 recruits the fork protection factor REV7 to stalled replication forks and prevents nucleolytic degradation.

MegaDNA, a long-context genomic language model, generates DNA sequences up to 96 K base pairs with annotated proteins and potential regulatory elements. It predicts essential genes, genetic variant effects, and regulatory element activity.

Here, the authors compile a global geochemical database of Neogene-Quaternary intraplate volcanism. By comparing the distribution and composition of these rocks with tomographic models they show that intraplate volcanism can be used to constrain upper-mantle structure at the time of eruption.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

Based on single worm whole genome sequencing, the authors here characterise the global evolution of the gastrointestinal parasite Haemonchus contortus and identify genes that play a role in drug resistance as well as climate-driven adaptations involving an epigenetic regulator.

H9T, an engineered IL-2 partial agonist, promotes the expansion of T cells while maintaining a stem-cell-like state, leading to improved efficacy of adoptive cell therapy in mouse models of melanoma and acute lymphoblastic leukaemia.

The nanoscale organisation of the brain extracellular space can be studied in vivo. Here, the authors investigate how it changes in response to α-synuclein pathology, and identify interactions between microglia and the extracellular matrix.

Detailed mapping of the distribution of water and semiheavy water in the coma of Halley-type comet 12P implies a D/H ratio that is consistent with that of Earth’s water, indicating a common heritage.

Recent studies unexpectedly indicate involvement of ventral tegmental area dopamine neurons in Alzheimer’s disease (AD). Here, the authors identified the enzyme casein kinase 2 as a mechanistic link between abnormal firing activity and AD pathology.

Aberrantly formed microglia due to an adverse prenatal environment affect long-term microglia reactivity and proper striatal circuit development in mice

PINNACLE is a context-specific geometric deep learning model for generating protein representations. Leveraging single-cell transcriptomics combined with networks of protein–protein interactions, cell type-to-cell type interactions and a tissue hierarchy, PINNACLE generates high-resolution protein representations tailored to each cell type.

The reticular activating system (RAS) of the brainstem regulates wakefulness, and stimulation of RAS areas can reverse effects of anaesthesia. Here, the authors show that stimulation of a particular RAS area, the anterior portion of nucleus gigantocellularis, can produce arousal from deep coma.

Understanding asteroid materials is critical for determining deflection methods for planetary defense. Here the authors show, via experiments performed in High-Radiation to Materials facility at CERN, that iron-rich asteroid materials can absorb more energy without structural failure than standard material parameters would suggest.

The architecture of planetary systems is shown to be strongly affected by stellar clustering in position-velocity phase space; hot Jupiters occur preferentially at high density, suggesting that their extreme orbits originate from environmental perturbations.

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.

Haploinsufficiency in three genes associated with risk of autism spectrum disorder—KMT5B, ARID1B and CHD8—in cell lines from multiple donors results in cell-type-specific asynchronous development of GABAergic neurons and cortical deep-layer excitatory projection neurons.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Here, the authors identify the microbiota-derived corisin as a driver of diabetic kidney fibrosis via cellular aging and show that targeting corisin with a monoclonal antibody alleviates disease in mice, suggesting a potential therapeutic avenue.

Proteome analysis of The Cancer Genome Atlas (TCGA) colorectal cancer specimens reveals that DNA- or RNA-level measurements cannot reliably predict protein abundance, colorectal tumours can be separated into distinct proteotypes, and that copy number alterations drive mRNA abundance changes but few extend to protein-level changes.

Enrichment for efferocytic macrophages in the islets of Langerhans promotes the accumulation of anergic-like CD4⁺ T cells and dampens autoimmune diabetes.

Memory B cells need to be reactivated to produce high affinity antibody responses on subsequent antigen encounters. Here the authors show that memory B cells localise to lymph node subcapsular proliferative foci (SPF), which have distinct properties from the germinal centre, for rapid expansion and the induction of B memory responses.