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Peroxisome Proliferator Activated Receptor alpha (PPARα) drives fatty acid catabolism. Here, the authors show that in liver of autophagy deficient class 3 phosphoinositide 3-kinase mutant mice PPARα transcriptional repressors fail to degrade in lysosomes and accumulate leading to PPARα inhibition and blunted transcriptional responses during fasting.

Perturbed B cell responses have been associated with Crohn’s disease. Here, the authors sequence the B cell receptor repertoire in patients with Crohn’s disease and identify shared B cell clones, thus implicating the presence of common Crohn’s disease-associated antigens driving a pathogenic B cell response.

Diatoms dominate the oceans, yet sexual reproduction - key to bloom dynamics and species evolvability - is rarely observed. Using a lab-to-field approach, this study presents conserved markers applicable across datasets, revealing widespread sex in both abundant and rare taxa in diatom natural populations.

This study maps the connections of layer 5 pyramidal neurons in the mouse cortex, revealing distinct local and intercortical wiring patterns, and provides an open framework for exploring the connectivity of cell types.

The standard method for identifying active brown adipose tissue is costly and exposes patients to radiation. Here, the authors show that convolutional neural networks can predict [¹⁸F]-FDG uptake by BAT from unenhanced CT scans and improve the segmentation accuracy compared to conventional CT thresholding.

Animals must distinguish between signals from sensory stimuli and action-generated signals. This paper shows that the ventral lateral geniculate nucleus acts as a corollary discharge center to suppress motion-induced visual signals, orchestrating accurate perception and motor control.

How sensory maps are formed in the brain is only partially understood. Here the authors describe spontaneous calcium waves that propagate across different sensory nuclei in the embryonic thalamus; disrupting the wave pattern triggers thalamic gene expression changes and eventually alters the size of cortical areas.

Cluster states are a key resource in quantum technologies, but generation of large-scale 2D cluster states faces several difficulties. Here, the authors show how to generate a 2 × n ladder-like cluster state via sequential emission of time- and frequency multiplexed photonic qubits from a transmon-based device.

Results from a phase 3 randomized controlled trial suggest that escitalopram is not effective in treating agitation in Alzheimer’s dementia and is associated with cardiac conduction delays.

Understanding gene expression involves studying the transcriptional effects of perturbations. Here, the authors monitor RNA transcripts after applying 83 epigenetic compounds, identifying responsive genes enriched with chromatin marks and regulators in line with their mechanisms of action.

A comparative analysis of morphological data across 149 species of Drosophilidae shows that sperm length in males has co-evolved with the length of the sperm-storage organ in females. Combining a genome-wide association study of these traits in Drosophila melanogaster with molecular evolutionary analyses of the genomes of 15 Drosophila species, the authors find that the genetic architecture underlying sperm length is associated with indirect genetic benefits in females, providing support for the ‘good genes’ hypothesis.

The clustered regularly interspaced short palindromic repeats (CRISPR) system protects prokaryotes from foreign DNA. Here, bacteriophage DNA containing mutations that can circumvent this response are shown to be incorporated into the CRISPR locus, allowing bacteria to remember previous infections in an adaptive manner.

The development of active solids based on centimetre-scale building blocks incorporating odd elasticity shows that they can spontaneously undergo limit cycles of shape changes, leading to adaptive locomotion such as rolling and crawling.

Analysis of a large cohort of metastatic breast cancer samples shows that APOBEC mutational signatures are enriched in post-treatment samples. APOBEC activity was also associated with mutations known to drive drug resistance.

This study uses single-cell sequencing to investigate the diversification of cortical cell types during evolution. Comparisons across brain regions and species identify molecular signatures of ancestral cell types in the mammalian olfactory cortex.

KDM4C regulates cathepsin L-mediated histone H3 N-terminal tail clipping through grainyhead-like 2 (GRHL2) methylation in breast cancer. This link between the cellular redox state and chromatin remodeling might represent a therapeutic target in KDM4C-amplified tumors.

Leukapheresis is prohibitive in newborns due to the large extracorporeal volume. Here, the authors develop a microfluidic device to perform leukapheresis on whole blood at clinically relevant flow rates and show its safety and efficacy in animals.

A bioengineered cornea made of collagen restores vision in a pilot clinical study.

The metal-organic framework TAMOF-1 offers high performance for CO₂ capture and purification from model biogas streams, thanks to its high CO₂ adsorption potential, good stability in humid conditions, and energy-efficient regeneration.

Inflammatory monocytes in the brain meninges promote stress-induced fear behaviour, and the pathways involved can be modulated using psychedelic compounds.

Previous studies suggest that rates of gorge formation are controlled by bedrock erodibility, erosion mechanism and hillslope processes. Here, the authors show evidence of rapid gorge formation in granite bedrock and report no relationship with flood size or bedload, attributing the rate to pre-existing jointing.

Using a combination of bioinformatics, biochemistry, genetics, genomics and cell-based approaches, this study shows that the H3–H4 binding capacity of the histone chaperone SPT2 is required to preserve chromatin structure and function in Metazoa.

The endosomal retrieval subdomain organizes recycling of endocytosed proteins. Here, using proximity proteomics, the authors reveal that this recycling subdomain regulates switching of specific RAB GTPases, a feature likely important in neuroprotection.

Although progress in the coverage of routine measles vaccination in children in low- and middle-income countries was made during 2000–2019, many countries remain far from the goal of 80% coverage in all districts by 2019.

CD8 T cells can protect the liver from viral infection, but can also result in severe liver damage and organ failure. Here, the authors develop a mouse model reflecting fulminant CD8 T cell mediated viral hepatitis, which occurs in a perforin-dependent manner that is protected by the use of perforin inhibitors.

Adipose manipulation transplantation can reduce tumor growth and proliferation in vitro and in mouse models.

Cancer cells frequently harbour genetic aberrations that protect them from programmed cell death. Here, the authors show in non-small cell lung cancer that the anti-apoptotic gene MCL-1 is subject to copy number gains and that deletion of MCL-1 reduces tumour formation.

Monoclonal antibodies show great promise in treating Covid-19 patients. Here, Maisonnasse, Aldon and colleagues report pre-clinical results for COVA1-18 and demonstrate that it reduces viral infectivity in three animal models with over 95% efficacy in macaques upper respiratory tract.

The antiviral dsRNA sensor PKR is regulated by PACT. This paper shows how PACT prevents aberrant PKR activation by endogenous dsRNAs like Alu. PACT disrupts PKR’s dsRNA scanning without blocking its binding, resetting its activation threshold to tolerate cellular dsRNA and preserve homeostasis.

Tests of the Bell-Kochen-Specker theorem aim at showing that the measurement statistics of a single qutrit are incompatible with noncontextual realism. Here, the authors use a superconducting qutrit with deterministic readouts to violate a noncontextuality inequality, ruling out several loopholes.

Combining conformal prediction machine learning with molecular docking, a method to efficiently screen multi-billion-scale libraries is developed, enabling the discovery of a dual-target ligand modulating the A_2A adenosine and D₂ dopamine receptors.

CD36 drives lymph node metastasis in breast cancer by activating YAP signaling-mediated anoikis resistance via inducing the PPARα-CYP7A1 bile acid biosynthesis pathway.

Observations of a fast X-ray transient reveal that it is a gamma-ray-burst explosion from a very distant galaxy that emits light with the wavelength necessary to drive cosmic reionization, the last major phase change in the history of the Universe.

Primary cilia are essential conveyors of signals underlying major cellular functions but their role in brain development is not completely understood. Here the authors compiled a shRNA library targeting ciliopathy genes known to cause brain disorders, and used it to query how ciliopathy genes affect distinct stages of mouse cortical development.

Ammonia represents a promising fuel resource, but its efficient conversion to dinitrogen faces high energy barriers. Now magnetic domain structures of Co/Pt thin films have been engineered to facilitate N–NH dimerization by cooperative spin alignment, revealing a spin-regulated pathway to enhance activity in catalytic nitrogen chemistry.

JWST data show that the exoplanet WASP-18b has thermally distinct regions of its dayside. The authors mapped the sizes of these regions, measured their temperatures and potentially identify water destruction in the hottest region.

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).

The neural mechanisms setting the lower limit of conscious visual perception in humans is not fully understood. Here the authors show by correlating human vision experiments and non-human primate retina recordings that primates rely on the retinal ON pathway in perception of the dimmest light increments, and that nonlinear thresholding in this pathway eliminates single photons and neural noise thereby allowing perception of minute differences in light intensity.

A versatile cloud-accessible single-photon-based quantum computing machine is developed, which shows a six-photon sampling rate of 4 Hz over weeks. Heralded generation of a three-photon Greenberger–Horne–Zeilinger state—a key milestone toward measurement-based quantum computing—is implemented.

Carramolino et al. show that fibromyocytes and chondromyocytes are selectively depleted, while cap cells are maintained, in regressing mouse plaques.

As the Plasmodium species that cause malaria replicate in the liver, Heath and colleagues designed mRNA vaccines to limit infection by inducing liver-resident memory T cells. Efficacy was observed in mice, including in hosts with previous blood-stage infection.

The wave nature of light and particles is of interest to the fundamental quantum mechanics. Here the authors show the double-slit interference effect in the strong-field ionization of neon dimers by employing COLTRIMS method to record the momentum distribution of the photoelectrons in the molecular frame

Tunable polarization control and a two-colour X-ray pump–X-ray probe operating mode are demonstrated at the Linac Coherent Light Source (LCLS).

The brain cell types of Octopus vulgaris that control their sophisticated behavioral repertoire are still unknown. Here, authors use single-cell transcriptomics to profile neuronal and glial cell types and compare cell type relationships within the octopus brain and across species.

Using seven generations of selected zebrafish (Danio rerio), the authors consider the trade-offs and mechanisms behind evolution of warming tolerance. They show unexpected improvements in cooling tolerance in warming-adapted fish, and highlight mechanistic insights behind warming tolerance.

A near-infrared fluorescent calcium indicator can be combined with other optogenetic tools in vivo without spectral crosstalk.