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Here the authors compare genetic testing strategies in rare movement disorders, improve diagnostic yield with genome analysis, and establish CD99L2 as an X-linked spastic ataxia gene, showing that CD99L2–CAPN1 signaling disruption likely drives neurodegeneration.

Understanding how each tumor establishes its unique spatial landscape and what factors drive the landscape for tumor fitness remains significantly challenging. Here, the authors employ spatial single-cell imaging and single-cell RNA sequencing to analyze 50 liver cancer biospecimens and find that different tumor cell states may be organized into distinct clusters, or ‘villages’.

Small-scale vorticity dynamics are central to turbulence, but their transient and chaotic nature makes direct measurement and control extremely challenging. By using magnetically driven particles, authors uncover stochastic resonance and a symmetry-breaking mechanism that may enable both control of particle dynamics and a magnetic resonance- based method for probing turbulence at its smallest scales.

Aggregates of misfolded proteins are sequestered in the aggresome via dynein transport in an aggregate size-dependent manner. Here, authors find episodic transport kinetics mediated by aggresome-dynein adapters are central to this size-filter effect.

RFdiffusion2, an extension of the RFdiffusion framework, builds de novo enzyme active sites using atom-level functional group constraints.

Top-down projections from the orbitofrontal cortex carry predictive signals that grow with sound experience and suppress the auditory cortex via inhibitory circuits, revealing a predictive mechanism for sensory habituation.

Several recent publications have attempted to detect novel unannotated microproteins using mass spectrometry proteomics. Here, the authors reassess these claimed microprotein detections, finding that many are poorly supported, while a subset represents likely genuine discoveries of novel proteins.

A suite of tools including positive-going voltage indicators, a high-speed two-photon microscope, and denoising software enables prolonged imaging of electrical activity in neurons with limited toxicity.

Telomerase recruitment to telomeres is a tightly regulated process which is stimulated by replication stress. Here, the authors identify that nuclear filamentous actin is important for interaction between telomerase and telomeres, ultimately facilitating productive telomere extension by telomerase.

Bright electron bunches power particle physics and photon science. Here, reproducible bunches were generated in a plasma with simultaneous high charge per unit energy and low emittance, advancing a scheme to produce ultra-bright bunches in future.

A strongly lensed galaxy at redshift z ≈ 6 is resolved into at least 15 star-forming clumps embedded in a rotating disk. Clump formation in this system, which is not predicted by cosmological zoom-in simulations, may be driven by disk instabilities with weak feedback, rather than past mergers.

Decoherence is anathema to quantum systems, as it reduces their performance and stability. Shulman et al.show that real-time Hamiltonian parameter estimation can significantly increase the coherence time of a qubit by enabling continuous adjustment of its control parameters.

Gap junction channels formed by Cx32 enable intercellular communication, and their disruption causes CMT1X disease. Here, authors use cryo-EM and molecular dynamics simulations to show how specific lipids and sterols may directly control Cx32 channel gating

Transcriptome-scale maps of RNA secondary structure ensembles in living cells detect candidate RNA structural switches.

How do low-mass binaries age? Astronomers have constrained a tight, circular orbit of a close-in companion around a dying giant star, raising new questions about how tidal forces shape binary orbits in the final phases of stellar evolution.

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.

The impact of variants of uncertain significance (VUS) on protein function and cancer risk remain unclear. Here, the authors focus on the functional impact of VUS of the PALB2 gene and identify defects in DNA damage repair by homologous recombination associated with increased risk of breast cancer.

Variants in NOS1AP can cause monogenic nephrotic syndrome. Here, the authors show that disrupting the intergenic NOS1AP splice isoform that is more prevalent in podocytes leads to monogenic kidney disease responsive to RAAS inhibition.

Stone tools illustrate behavioural complexities in Middle Pleistocene hominin populations. Here, the authors present small dimensional flakes and hafted tools from Xigou, central China, dated to ~160–72 thousand years ago that demonstrate early, complex technological advancements.

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.

The physiology and behavioral function of proprioceptors that detect joint limits are not fully understood. In this study, the authors used calcium imaging, optogenetics, behavioral genetics, and the connectome to demonstrate that hair plate proprioceptors on the fly leg detect joint limits and engage circuits to drive the leg away from those limits.

A two-component system, DbfRS, regulates biofilm formation in Vibrio cholerae. Here, Nguyen et al. identify a small periplasmic protein that controls the activity of the system’s receptor, and show that DbfRS responds to membrane stress and regulates additional processes such as metabolism and cell envelope biosynthesis.

Although our nearest neighbour, the Andromeda galaxy, is falling towards us, slightly more distant galaxies all move away with the cosmic expansion because they are being pulled by a giant dark matter sheet.

Little Red Dots (LRDs) are a high-redshift galaxy population with unclear nature. Here, authors show CANUCS-LRD-z8.6, a spectroscopically confirmed LRD, hosting an active galactic nucleus, and its properties provide insights for early black hole and galaxy formation.

Nonsense variants can disrupt gene function, but regional intolerance is poorly defined. Here, the authors develop a map of regional intolerance to nonsense mutations, improving loss‑of‑function variant interpretation and prioritising novel genes in rare disease.

Gas-phase actinium monofluoride (AcF) has been produced and spectroscopically studied at the CERN-ISOLDE radioactive ion beam facility; the results highlight the potential of ²²⁷AcF for exceptionally sensitive searches of CP violation.

A three-dimensional imaging system which distributes the optical illumination over the full field-of-view is sought after. Here, the authors demonstrate the capability of reconstructing 128 × 128 pixel resolution three-dimensional scenes to an accuracy of 3 mm as well as real-time video with a frame-rate up to 12 Hz.

Lewis et al. identify lamin B receptor (LBR) and lamina-associated polypeptide 2 (LAP2) as major factors that tether heterochromatin to the envelope. Deletion of these proteins causes changes in 3D genome organization, gene expression and cell fate determination.

Optogenetic manipulation of spindle dynamics reveals that microtubule shortening at kinetochores limits spindle elongation rather than moving chromosomes, revealing local chromosome–spindle interactions.

This study explores the complex dynamics of slow laboratory earthquakes, revealing how fault structures evolve and influence slow seismic slip. Using a transparent experimental setup and a high-speed camera, real-time deformation and stress redistribution are observed within simulated fault zones made of clay.

The substantia nigra and all Parkinson’s disease deep-brain stimulation targets are selectively connected to the somato-cognitive action network rather than to effector-specific motor regions.

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.

To express a biosensor in primate cortex, multiple injections of virus carrying the sensor gene are necessary. Here, the authors develop an automated robotic system for multiple, safe injections.

Gravitational lens modelling of a million-solar-mass dark object reveals that it cannot be a free-floating black hole or dark-matter halo as predicted by cold dark matter, instead indicating a peculiar and highly concentrated mass distribution.

How the brain maintains object representations during grasping, when complex sensory input rapidly changes, remains poorly understood. Here the authors show that object-identity signals shift and strengthen across sensorimotor cortex as reaching transitions to grasping.

Molecular core levels are localized around a single atomic site, but for indistinguishable atoms, photoionised core-holes can either be seen as localized or delocalized. Using a prototypical symmetric system, CS₂, Guillemin et al. show that these states can be disentangled by fragmentation dynamics.

R2SP belongs to the R2TPlike quaternary chaperone family and consists of RUVBL1/RUVBL2 AAA+ ATPases, SPAG1 and PIH1D2. Here, authors combined biochemistry, NMR, structural MS and cryo-EM to investigate its 3D organization, mode of assembly and ATPase activity.

An optimal model-experiment integration for testing many complex hypotheses is still lacking. Here authors introduce improv, a modular software platform enabling real-time adaptive neuroscience experiments, orchestrating parallel data collection, modeling, and experimental control. Authors demonstrate various use cases, including online neural analysis and closed-loop optogenetics in zebrafish.

Post-transcriptional regulation of mRNA translation was explored using Ribo-STAMP and single-cell RNA sequencing to reveal cell-type-specific and isoform-specific translation patterns across hippocampal neuronal and non-neuronal cell types, highlighting functional differences between CA1 and CA3.

ALMA has captured exquisitely detailed images of bowshock shells in the outflow of an outbursting protostar. These provide important insights into the variable nature of the ejections from protostars, which play a key role in star and planet formation.

Many single cells rely on beating cilia and flagella to move. Now it is shown that the core of these appendages twists to generate the torsion waves responsible for three-dimensional motion.

The vacuum process is scalable and solvent free, yet all-vacuum-deposited perovskite solar cells still trail solution-processed counterparts. Facet-directed co-evaporation yields (100)-oriented mixed-halide wide-bandgap films for efficient, stable single-junction cells and perovskite–silicon tandem cells.

This study identifies AcuB as a conserved inhibitor of the deacetylase AcuC in bacteria. AcuB directly suppresses AcuC activity, and this inhibition is enhanced the alarmone diadenosine tetraphosphate, linking stress signaling to acetylation control.

The accepted function of hypothalamic retinal input is regulation of daily rhythms in physiology and behaviour. Here authors show it also supports detection of form and motion and regulates visually-guided behaviours, via the lateral hypothalamus.

It is known that liquid drops can be levitated by continuous vapour flow above a liquid surface. Here the authors combine the ultra-low friction provided by the bath with the interaction force between two drops due to interface deformations to study the dynamics of interactions between multiple objects.