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The developmental origin of behavioral individuality is unclear. The authors show that a temporal sequence of genetically encoded stochastic mechanisms explains variation in stereotyped neuronal circuits.

In the second case in which a genetically modified pig heart was transplanted into a living person, the xenografted heart functioned well initially, but antibody-mediated rejection occurred thereafter, pointing to the need for improved strategies to avoid this complication.

In proliferative retinopathies, pathological vessels replace healthy ones, impairing vision. Here, the authors show that reprogramming the metabolic environment of retinal blood vessels from fatty acid oxidation to glycolysis promotes healthy revascularization and improves vision in proliferative retinopathy.

Currently, there is an urgent need to evaluate the strengths and limitations of various probe-based full transcriptome methods for formalin-fixed paraffin-embedded tumor tissues. Here, the authors analyze three commonly used methods and highlight relative advantages and disadvantages of each method in the context of operational challenges, bioinformatic analyses and biological discoveries.

A phase 1/2 clinical trial of a new device-assisted therapy in Parkinson’s disease revealed that intracerebroventricular administration of anaerobic dopamine was safe and significantly reduced l-dopa-related complications.

HistoPlexer, a deep learning model, generates multiplexed protein expression maps from H&E images, capturing tumour–immune cell interactions. It outperforms baselines, enhances immune subtyping and survival prediction and offers a cost-effective tool for precision oncology.

To evaluate the effectiveness of current national policies in achieving global temperature targets is important but a systematic multi-model evaluation is still lacking. Here the authors identified a reduction of 3.5 GtCO₂ eq of current national policies relative to a baseline scenario without climate policies by 2030 due to the increasing low carbon share of final energy and the improving final energy intensity.

Previous work has shown that electronic and structural transitions in VO₂ can be decoupled by realizing an electronic transition within a monoclinic phase. Here, the authors extend this to the rutile phase by demonstrating a photodoping-driven transition from an insulating to a metallic rutile phase.

The study on APOE4 homozygosity indicates a genetic variant of Alzheimer’s disease with early symptom onset and distinct biomarker progression, highlighting the need for specialized treatment approaches.

Cholera continues to cause significant mortality in endemic regions such as Bangladesh where diverse lineages circulate. Here, the authors investigate genomic features that are associated with linage transmission dynamics and disease severity using machine learning, genome-scale metabolic modelling, and 3D structural analysis.

Here the authors use tensile strain imposed by artificial substrates of LaLuO3 to stabilize a pure antiferroelectric phase in epitaxial thin films of PbZrO3.

This study demonstrates the role of non-local exchange and correlation interactions in solid electrolytes (SEs) for lithium-ion batteries. Through analysis of argyrodite SEs, it reveals how non-local interactions influence lithium diffusion and structural stability, guiding future SE design.

A high-resolution, global atlas of mortality of children under five years of age between 2000 and 2017 highlights subnational geographical inequalities in the distribution, rates and absolute counts of child deaths by age.

Wood and colleagues report that the XPO1 inhibitor selinexor activates PI3Ky-dependent AKT signaling in AML via upregulation of P2RY2 and demonstrate a synergistic effect of combining selinexor with inhibition of prosurvival AKT signaling.

SOCS1 is a potent suppressor of JAK-STAT signalling responses to IFNγ and γ-chain cytokines and thereby limits inflammation. Here the authors identify and characterize heterozygous SOCS1 mutations in 10 patients from 5 unrelated families with autoimmune diseases.

The functional organization rules of retinal orientation are not fully understood. Here the authors show that orientation detection, a crucial task for visual perception, is organized in the mouse retina along concentric axes, and that this organization develops even in the absence of visual experience or patterned spontaneous activity.

Tn-seq and live imaging of Pseudomonas aeruginosa during airway epithelial organoid infections reveal metabolic adaptations and trade-offs between growth and antibiotic tolerance in biofilm lifestyle, impacting bacterial spread and cytotoxicity.

Senescence induction is known to induce stable proliferation arrest. Here, the authors show that sustained PARP inhibition promotes a reversible p53-independent senescence, and that PARP inhibition is synthetic lethal when combined with senolytic agents in pre-clinical models of ovarian and breast cancer.

Subthalamic deep brain stimulation produces evoked resonant neural activity (ERNA) which has been linked to therapeutic benefit. Using a multimodal approach, the authors propose that ERNA reflects activation of the basal ganglia indirect pathway network.

Studying the impact of SARS-CoV-2 on organelle dynamics may shed more light on the mechanisms of viral replication. Here, the authors combine label-free holotomographic microscopy with AI to study subcellular changes and organelle dynamics upon SARS-CoV-2 infection.

Naderi et al. show that increasing the dispersion of aromatic residues in intrinsically disordered regions of human transcription factors enhances their activity but reduces their specificity.

The radial-velocity technique could detect a small gas giant orbiting a binary star and determine its mass: 65.2 ± 11.8 Earth masses. The system also hosts a smaller inner planet, making it one of the few known multiplanetary circumbinary systems.

Using a haplotype-based approach, David-Alexandre Trégouët and colleagues report that the SLC22A3-LPAL2-LPA gene cluster is associated with risk of coronary artery disease.

Deep brain stimulation programming for Parkinson’s disease entails the assessment of a large number of possible simulation settings, requiring numerous clinic visits after surgery. Here, the authors show that patterns of functional MRI can predict the optimal stimulation settings.

Inadequate processing characteristics and performance are major obstacles to the broader adoption of sustainable polymer materials. Here, the authors show that co-assembly of oligopeptide-based polymer end groups and a corresponding low molar mass additive leads to a hierarchical structure, resulting in materials with improved processability and mechanical properties.

This study estimates the reproductive potential of fish in globally distributed coral reef sites. The results show substantial gains in reproductive potential can be achieved through the 30 × 30 conservation target, particularly for the important fisheries family, Serranidae, demonstrating the possible benefit of protection to population replenishment.

Analysing >1,700 inventory plots from the Amazon Tree Diversity Network, the authors show that the majority of Amazon tree species can occupy floodplains and that patterns of species turnover are closely linked to regional flood patterns.

Over time, paralogous genes accumulate changes in their sequences that do not affect their function, which is called cryptic variation. Using paralogous myosins, this study shows how cryptic variation modulates the functional effect of mutations and biases duplicates to distinct evolutionary fates.

Hypothalamic melanocortin neurons control energy homoeostasis by modulating appetite. Here, the authors reveal a role for the transcription factor Tbx3 as a regulator of the peptidergic identity and function of immature and mature mouse melanocortin neurons.

Deregulation of the Phosphoinositide 3-kinase (PI3K) pathway is associated with metabolic flexibility leading to cancer poor prognosis. Here, the authors show that targeting both glutamine degradation and mTOR inhibition effectively kills PI3K-altered cancer cells in pre-clinical and clinical settings for T-cell acute lymphoblastic leukemia and solid cancer.

The modelling of human-like behaviours is one of the challenges in the field of Artificial Intelligence. Inspired by experimental studies of cultural evolution, the authors propose a reinforcement learning approach to generate agents capable of real-time  third-person imitation.

Bayesian Flow Networks generate diverse, novel, and coherent protein sequences, surpassing prior unconditional generation methods. They also permit flexible conditional generation during inference, which is demonstrated on antibody inpainting tasks.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

Myelofibrosis is a form of myeloproliferative neoplasm with few treatment options available. Here, the authors profiled drug responses and proteomics ex vivo and identify molecularly-guided treatment strategies, including HDAC and BET inhibitors for CALR mutant myelofibrosis patients.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Human cortical maturation is organized along the sensorimotor-association axis. Here, the authors investigate in multiple cohorts if the development of functional connectivity during adolescence conforms to this hierarchy.

Inventory data from more than 1 million trees across African, Amazonian and Southeast Asian tropical forests suggests that, despite their high diversity, just 1,053 species, representing a consistent ~2.2% of tropical tree species in each region, constitute half of Earth’s 800 billion tropical trees.

Coquand, Brunet Avalos et al. develop an imaging method to map basal radial glial cell division in human fetal tissue and cerebral organoids and detect abundant symmetric amplifying, but also direct neurogenic divisions bypassing intermediate progenitors.

Models of perceptual decision making typically take into account either reactive responses to external stimuli or proactive aspects to decision making. Here the authors found that rat perceptual responses are generated by a combination of the standard evidence accumulation process with a fixed decision boundary, and a separate stochastic boundary collapse triggered by a parallel proactive process.

Relevant features of T cell repertoire in human cancer remain to be delineated. Here the authors show, by TCR sequencing in a large cohort of lung cancer patients, that while a majority of T cell clones are shared between tumor and adjacent lung tissue, less frequent tumor-unique T cell clones correlate with worse prognosis.

Combined intraocular injection of an adeno-associated viral vector, encoding an optogenetic sensor, with light stimulation via engineered goggles enables partial recovery of visual function in a blind patient.

Observations from the Labrador Coast indicate the presence of subsea permafrost landforms outside of the Arctic, suggesting a potential underestimation of subsea permafrost in the world’s oceans.

Bacteria in the same environment can share genetic material but the extent to which this influences development of antimicrobial resistance is unclear. Here, the authors investigate the evidence for co-evolution of antimicrobial resistance in bacteria found coexisting in animals and the environment in chicken farms and slaughterhouses in China.

Optical aberrations can hinder fluorescence imaging of thick samples, reducing image signal, contrast, and resolution. Here, the authors introduce a deep learning-based strategy for aberration compensation, improving image quality without slowing image acquisition or introducing more optics.

A Homo aff. erectus individual dated to 1.4 million to 1.1 million years ago found at Sima del Elefante (Sierra de Atapuerca, Spain) does not display the modern-human-like aspect of Homo antecessor found at the neighbouring Gran Dolina site (900,000–800,000 years ago).