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The human mitochondrial helicase Twinkle is essential for maintaining mitochondrial DNA. Here, the authors combine biochemical and single-molecule approaches to show how Twinkle’s real-time kinetics are regulated by its amino and carboxyl terminal domains, revealing a key auto-regulatory mechanism.

Engineering motif-specific 'hot spots' into an antibody scaffold yields antibodies with high affinity to targets containing phosphoserine, phosphothreonine or phosphotyrosine.

In this study, the authors model the current mechanical properties of the seafloor of Jupiter’s icy moon Europa, and find those rocks to be too strong to allow the kind of fracturing that, on Earth, enables rock–water chemical reactions on which chemosynthetic life relies.

Structural, genetic, functional and biochemical analyses of the complex flagellar motor of Campylobacter jejuni reveal structural adaptations with an ancient origin also found more widely across bacterial species, including elements exapted from the type IV pilus machinery.

Bessler et al. developed a human organoid model for H3.3K27M-altered diffuse midline glioma that recapitulates key tumor features and demonstrated its utility for modeling CAR T cell and microglia functions.

Targeting FSP1 in lymph nodes has considerable potential for blocking melanoma progression.

Lipid phosphate phosphatases (LPPs) catalyze the dephosphorylation of bioactive lipid phosphates. In this study, the authors employ structural and biochemical investigations on human LPP1, elucidating its catalytic mechanism and suggesting a potential regulatory role for PIP₂.

The microbiota influences the cytotoxicity of chemotherapy in patients with colorectal cancer but the impact on metastatic relapse is less clear. Here, the authors report that chemotherapy-induced intestinal mucositis induces systemic immune changes via production the microbial metabolite, indole-3-propionic acid (IPA), preventing metastases.

CELSR1 is a core component of the tissue/planar cell polarity pathway. Here, the authors report a CELSR1-related disorder featuring brain malformations, neurodevelopmental delay and epilepsy, and use mice to explore the pathophysiological mechanisms.

A technique called LICONN (light-microscopy-based connectomics) allows mapping of brain tissue at synapse level and simultaneous measurement of molecular information, thus enabling quantification of cellular properties and multimodal analysis of brain tissue.

Block copolymer self-assembly enables complex nanostructures including spherical micelles, continuous cubic gyroids and Frank-Kasper phases. Here, the authors show how film surface self-assemblies of binary and ternary block copolymer micelle alloys pave a path to controlled multicomponent assemblies.

AvrPm4 is a chimeric powdery mildew effector that is recognized by the wheat kinase fusion resistance protein Pm4. The pathogen can evade Pm4 recognition by expressing the suppressor SvrPm4, an RNase-like effector with multiple roles.

Promoter escape is a key step in bacterial transcription and a target of the antibiotic rifampicin. Here, the authors use cryo-EM to explore this step, finding seven structural intermediates of M. tuberculosis RNA polymerase during promoter escape.

LSFM imaging revealed 3D islet maps: GADA+ cases mirrored controls, while short-duration T1D showed loss of small INS + GCG– islets but preserved larger mixed INS + GCG+ ones, highlighting islet size- and composition-dependent vulnerability

Nuclear biomolecular condensates are functional sub-compartments within the cell nucleus. Here, the authors develop a synthetic DNA protonucleus that enables RNA transcription and condensation into diverse nuclear patterns, revealing insights into phase separation in nucleus-mimetic environments.

How site-specific tumor microenvironment (TME) drives the metastasis of high-grade serous ovarian cancer (HGSOC) remains unclear. Here, the authors employ an integrated single cell multi-omics approach to map the spatiotemporal heterogeneity of HGSOC metastasis TME and identify an interaction network within the TME driven by SELENOP⁺ macrophages and pre-exhausted CD8⁺ T cells.

Auditory stereocilia are mechanosensitive protrusions with precise dimensions that are formed around a core of long actin filaments. Here, the authors discover that stereocilia widening requires a population of myosin-regulated short actin filaments.

Crystal structures of HIV Env trimer with native glycosylation in complex with neutralizing antibodies reveal a glycan shield of high-mannose and complex-type N-glycan and indicate a path for germline-targeting vaccine design.

Liu et al. show that SPIN90 dimerizes and binds two Arp2/3 complexes to nucleate two bidirectional actin filaments and the dimerization domain is conserved in multicellular animals, suggesting that the mechanism of bidirectional actin filament nucleation is conserved.

Development of morphine tolerance is a critical medical and social issue. Here, the authors use single-molecule imaging to identify interaction sites of opioid receptor heterodimers and demonstrate that a soluble µ-δ heterodimer blocker peptide reduces tolerance in mice.

Yan et al. elucidated how the airway and the esophagus split from the foregut tube during embryonic development. They showed that collective migration of mesenchymal cells generates a constricting biomechanical force critical for splitting the epithelial tube.

Miyoshi and colleagues propose STELLA-SPIM microscopy to visualise single MYO7A molecules in live murine inner ear hair cells. Their data suggest that MYO7A traffics as a dimer within stereocilia to assemble the mechanoelectrical transduction machinery.

Foamy macrophages are key to atherosclerosis but poorly understood. Here, the authors show that GPNMB regulates lipoprotein processing in macrophages, exacerbating pathological lipid accumulation, and revealing it as a therapeutic target whose inhibition reduces atherosclerosis in mice.

Cadherin-based junctions connect cells to support tissue architecture. Here, the authors show that the condensation of core component β-catenin organizes cadherin complexes into clusters to promote formation of new adhesions.

Arya et al. report that migrating neutrophils resolve acute inflammation by releasing exosomes associated with nuclear DNA. This process is distinct from the release of neutrophil extracellular traps, and relies on the lamin B receptor.

An organoid system comprising adult mouse hepatocytes, cholangiocytes and mesenchymal cells recapitulates liver morphology, biliary function and fibrotic pathology, providing a new model for studies of hepatic biology.

pH is a critical regulator of (bio)chemical processes and therefore tightly regulated in nature. Now, proteins have been shown to possess the functionality to drive pH gradients without requiring energy input or membrane enclosure but through condensation. Protein condensates can drive unique pH gradients that modulate biochemical activity in both living and artificial systems.

How animals detect external touch while their sensory organs are in constant motion remains unclear. Here, the authors show that specialized receptors in rat whisker follicles are structurally tuned to ignore self-motion and respond only to touch.

The T-cell receptor (TCR) activation mechanism has remained uncertain. Here, the authors present molecular structures for the apo and ligand-bound human TCR–CD3 complex in lipid nanodiscs, revealing large conformational changes during activation.

Chronic inflammation affects the male reproductive system, contributing to infertility. Using a mouse model of epididymitis, here, the authors report on the formation of tertiary lymphoid structures (TLS) under conditions of chronic inflammation, and show that TLSs sustain immune activation, contributing to anti-sperm autoantibody production and epididymal injury.

Using two-photon microscopy with a panoramic virtual reality setup, how head direction cells in larval zebrafish integrate visual landmarks and optic flow to track orientation is revealed.

Engineering structurally and functionally complex synthetic cells remains a key challenge. Here DNA condensate synthetic cells combine phase separation and DNA nanostructures to reveal how switchable artificial cytoskeletons assemble in viscoelastic confinements. These cytoskeletons improve the mechanical properties of synthetic cells and enable stable mechano-interfaces with mammalian cells.

SWING is a versatile interaction language model that can learn the language of peptide and protein interactions.

Ribosomes convert chemical energy to mechanical work. Here, the authors monitor ribosome binding to the GTPase EF-G and the ensuing mechanical work on mRNA in real time, uncovering a major energetic contribution from EF-G binding, rather than GTP hydrolysis, to the mechanical work.

The flexibility of CRISPR/Cas9 editing is severely constrained by the requirement that the modification site is located in close proximity to the landing sequences. Here, authors develop a universal strategy that allows CRISPR-based editing at any position with high efficiency.

Breakage of both chromosomal DNA strands creates unique problems for DNA repair. Here, Luthman et al. show that for some broken ends, the two strand breaks are repaired in parallel, while for other ends one strand must be repaired before the other.

Errors in oocyte division can cause infertility and birth defects. Here, authors combine a genetic strategy with a novel optochemical tool to show that spindle pole-localized F-actin is essential for proper meiotic spindle assembly and chromosome segregation.

Here, the authors show that a single Lgr5 stem cell population in the posterior tongue produces taste buds, salivary glands, and epithelium, representing unified chemosensory units.

The mechanisms regulating central nervous system remyelination efficiency are poorly understood. Here, the authors show that remyelination is driven by astrocytes supporting oligodendrocyte survival, regulated by the Nrf2 and cholesterol pathways.

The presence of CD8⁺ T cells in the cytoplasm of biliary epithelial cells (BEC) has been associated with primary biliary cholangitis. Here, the authors demonstrate that CD8⁺ T cells invade BEC using a mechanism that is dependent on cytoskeletal rearrangements and E-cadherin:β-catenin interactions.

Machine learning expands quantum chemistry’s reach, but it struggles to generalize to unseen chemistry. Here, the authors develop a real-space learning strategy based on energy densities to build highly transferable quantum-chemical models.

Dinoflagellates and cyanobacteria produce saxitoxin (STX) congeners that block voltage-gated sodium channels. Here authors show how amphibians may sequester STX congeners using a ‘lock and key’ mode, expanding the understanding of toxic sponge action.

Bacteria secrete polysaccharides essential for colonization and infections. Here, the authors reveal the structure and mechanism of WzaB, a Class-3 OPX protein, uncovering a distinct trans-envelope secretion complex driving critical polysaccharide export in diderm bacteria.

MsbA mediates the transport of lipopolysaccharide across the inner membrane. Here, the authors show specific MsbA-lipid interactions can tune the selectivity for binding ATP over ADP and present five structures of MsbA with one bound to lipid.

REEP domain-containing proteins generate membrane curvature, and some are known to shape the endoplasmic reticulum (ER). Here, the authors show that four understudied members, REEPs 1-4, localize to vesicles that appear to bud out of, and fuse back with, ER.

Feng et al. uncover a retrograde trafficking route from the plant vacuole, showing that sorting nexins retrieve the plant-specific SNARE VAMP727 and revealing distinct pathways from the core retromer system.

Research on pain often relies on animals, and there is always a need for more precise and more ethical tools. Here, authors present a light-activatable molecule that induces pain in freely moving animal models in a reversible, non-invasive, and spatiotemporally defined way.

Using pear as a study system, the biosynthetic pathway of acetophenones has been elucidated: naturally impaired side-chain shortening of aromatic 3-ketoacyl-CoAs leads them to undergo hydrolysis, followed by decarboxylation, to yield acetophenones.

Flicker noise limits the performance of electronics. Here, the authors demonstrate in nanowires of charge-density wave materials (TaSe₄)₂I and NbS₃ that low-frequency electronic noise is suppressed below the limit of thermalized charge carriers in passive resistors.