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Hepatitis C virus remains a health burden due to the lack of an effective vaccine, hindered by difficulties in replicating the native E1E2 antigen structure. Here, the authors engineer a stabilized E1E2 heterodimer using cryo-EM-guided modifications, enhancing immunogenicity and paving the way for future HCV vaccine development.

Analyses of snRNA genes in a French cohort of people with rare disorders, with validation through international collaboration, identify monoallelic and biallelic variants in RNU2-2 as frequent causes of neurodevelopmental disorders with epilepsy.

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.

When 100 social and behavioural science claims were examined, 34% of reanalyses closely matched the original results, with 74% reaching the same conclusion, revealing limited robustness of single-path analyses and the need to address analytical uncertainty.

Robustness checks and reproduction of analyses with existing and updated data based on 110 articles in economics and political science journals with data and code-sharing requirements found high levels of robustness and reproducibility and determined that robustness was not dependent on author characteristics or data availability.

INSTALL overcomes fundamental challenges for DNA delivery and integration methods by synergizing immune-stealth nucleic acids with recombinases to enable kilobase-scale integration strategies without viral vectors.

The authors present a comprehensive plant-specific modelling framework for CRISPR gene drives: dormant seed banks can slow spread and require larger releases but can also ease weed elimination and limit unintended spread to nearby populations.

MAU2’s role in Cornelia de Lange syndrome was unclear. Here, the authors identify pathogenic MAU2 variants that disrupt NIPBL–MAU2 function, define MAU2‑specific episignatures, and show variable CdLS‑related phenotypes, supported by a Mau2 knockout mouse model.

Manipulating chemical interactions is crucial in protein assembly. Here, the authors highlight the importance of accounting for solvent forces mediated by interfacial hydration structures when designing protein assemblies at liquid-crystal interfaces.

A technique called condense-seq has been developed to measure nucleosome condensability and used to show that mononucleosomes contain sufficient information to condense into large-scale compartments without requiring any external factors.

Brown adipocytes are embedded within an intricate network of blood vessels and sympathetic nerves that support their development and thermogenic function. This study shows that adipocyte progenitor cells control blood vessel growth and nerve wiring in brown fat during cold exposure. They do so by releasing Slit3, which is cleaved into fragments that coordinate angiogenesis and sympathetic innervation.

Natural Killer cells are key mediators of anti-tumour immunosurveillance and anti-viral immunity. Here, the authors map regulatory genetic variation in primary Natural Killer cells, providing new insights into their role in human health and disease.

Insulin signaling plays a crucial role in coordinating skeletal development with whole‑body energy metabolism. Here, the authors use phosphoproteomics to show insulin-signaling rewiring in aged, insulin-resistant bone and identify defective phosphorylation of AFF4 as a key mechanism for regulating gene-specific transcriptional activation.

Using efficacy estimates from a previous cluster randomized trial in Senegal and accounting for differences in weather, vegetation and population density between trial and non-trial areas, a machine learning-enabled method estimates intervention efficacy for mass drug administration against malaria at a granular scale and beyond the trial period.

JWST phase-curve observations reveal that the two innermost TRAPPIST-1 planets emit thermal radiation consistent with bare rocky surfaces, indicating that both lack thick atmospheres.

Element-element bonded multiply charged cationic species are well known as dimers or small cyclic oligomers in the condensed phase but the smallest acyclic version, a trinuclear unit possessing greater than a monocationic charge, has remained elusive. Here the authors report a bis(phosphine) supported low valent triantimony-based tricationic compound.

Parsimonious deep neural network models can be used for prediction of visual neuron responses.

ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

Single-nucleus chromatin and RNA sequencing identifies epigenetic chromatin domains that confer vulnerability to paediatric brain tumours such as ependymomas, providing insight into the development of such tumours despite ‘quiet’ genomes.

Encoding quantum information in qudits instead of qubits allows for several advantages, but scalable native entangling techniques would be needed. Here, the authors show how to use light-shift gates to perform entangling operations on trapped ion systems, with a calibration overhead which is independent on the qudit dimension.

The production of high-value chemicals can involve energy-intensive processes, necessitating sustainable production strategies. Here the authors present a circular bioeconomy approach, upcycling plastic waste through microbial conversion into levodopa, a medicine for Parkinson’s disease.

This study presents an organ-wide spatial transcriptomic analysis of human skin from different anatomical sites using a combination of MERFISH technology and existing datasets from healthy and diseased skin.

Aird et al. report that promyelocytic leukaemia (PML)-localized speckled protein 110 (SP110) controls SP100 oligomerization, which then regulates the mitotic dissolution of nuclear PML bodies.

An analysis of whole-exome sequencing data linked to longitudinal electronic health records from 44,028 British South Asians finds new gene–phenotype associations and identifies 2,991 genes with rare biallelic predicted loss-of-function genotypes.

Here, the authors show that early-life high-fat/high-sugar diet induces sex-specific alterations in adult feeding behavior, hypothalamic transcriptome and blood metabolome, with Bifidobacterium longum and prebiotic FOS + GOS administration restoring these effects via distinct mechanisms, highlighting their therapeutic potential.

The development of an in silico typing database for Escherichia coli ABC transporter-dependent capsules enables analysis of capsule epidemiology and evolution for blood stream infection-associated E. coli.

An integrated lithium niobate–semiconductor platform generates topological soliton frequency combs on-chip, enabling turn-key, dispersion-agnostic comb sources without high-Q resonators or complex stabilization.

Machine learning upscaling analyses of global FLUXNET carbon and water flux measurements indicate that dryland vegetation productivity showed a negligible increase between 1982–2000 and 2001–2022, whereas humid-region vegetation productivity exhibited a nearly constant increase.

Myocardial infarction disrupts cardiac repair mechanisms, limiting regeneration. Here, the authors show that extracellular matrix therapies activate spatial and cell-specific pro reparative programs, revealed through spatial transcriptomics and snRNA-seq.

Hepatic glycogenolysis is essential for protein glycosylation and rhythmic secretion by the liver. Disruptions to hepatic glycogenolysis, caused by congenital diseases or physiological factors such as obesity, caloric restriction and changes to meal timing, alter hepatic protein secretion.

Bulk polyadenylation improves the capture of microbial RNA, enabling host–microorganism interactions to be visualized at a high resolution when combined with commercially available spatial transcriptomics platforms.

The cytoplasm can be partitioned into distinct compartments by microtubule structures, which can be stabilized by distinct mechanisms in different species.

Analysis of soundscape data from 139 globally distributed sites reveals that sounds of biological origin exhibit predictable rhythms depending on location and season, whereas sounds of anthropogenic origin are less predictable. Comparisons between paired urban–rural sites show that urban green spaces are noisier and dominated by sounds of technological origin.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Transcription factor osr2 is identified as a specific marker and regulator of mural lymphatic endothelial cell (muLEC) differentiation and maintenance, and muLECs and border-associated macrophages share functional analogies but are not homologous, providing an example of convergent evolution.

Smyth et al. demonstrate that a cellular inhibitor of apoptosis, cIAP2, exacerbates inflammation and cardiac injury after myocardial infarction and that its inhibition, either genetically or via Smac mimetics, offers a promising immunotherapeutic strategy to reduce post-MI damage and progression to heart failure.

Pastoralism spread through cultural diffusion into the Green Sahara, where an isolated, distinct North African ancestry persisted.

The use of harmful solvents to fabricate stable devices hampers the commercialization of perovskite solar cells. Here, the authors introduce a biorenewable solvent system and precursor-phase engineering to realize stable formamidinium lead triiodide-based solar cells.

Plasma p-tau217 tests used to develop clocks that predict when cognitively unimpaired individuals would develop symptoms of Alzheimerʼs disease.

The precise manipulation of unfunctionalized hydrocarbons remains a fundamental challenge in chemical synthesis and catalysis. Here an organocatalytic asymmetric hydroxylation of bicyclobutanes with alcohols is disclosed, enabling efficient access to tertiary cyclopropylcarbinyl ethers with high enantioselectivity (up to 98:2 e.r.).

TREM2 is an important AD risk factor playing essential roles in the microglial response to amyloid pathology. Here, authors show using a TREM2 reporter mouse that TREM2 levels are critical for efficacy of TREM2 agonism informing current clinical efforts.

Allcott et al. conducted an experiment in 2020, removing political ads from the feeds of randomly selected Facebook and Instagram users. There were no statistically significant effects on political outcomes such as knowledge, polarization and turnout.

The chemosensing accuracy of E. coli cells is shown to be limited by internal noise in signal processing, rather than the stochasticity of molecule arrivals at their receptors, contrary to long-held understanding in the field.

Schober and colleagues show that effector CD8⁺ T cells undergo metabolic shutdown, CD8⁺ central memory T cells are the most metabolically active, and naive-like memory T cells are quiescent during the acute phase of the immune response and represent the dominant population of memory CD8⁺ T cells after yellow fever vaccination in humans.

The zebra finch robust nucleus of the arcopallium (RA) directs singing by providing descending projections to brainstem motor neurons. The authors show that electrophysiological characteristics of RA neurons rely on resurgent Na+ currents that emerge early during song development only in males.

Neural mechanisms underlying motivation-driven behaviors are not fully understood. Here authors show that non-cholinergic neurons in rodent basal forebrain link sensory stimuli with motivational states and experience-driven plasticity.