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An allosteric site on the E3 ligase adapter cereblon can be targeted to modulate the efficacy of cereblon in targeted protein degradation applications.

Bohlen and colleagues report that the E3 ubiquitin ligase CBL is necessary for the development, tolerance and activation of B cells in humans, unlike in mice where CBL deficiency results in loss of T cells.

Microhomology-mediated end joining (MMEJ) and mitotic DNA synthesis (MiDAS) are critical DNA repair pathways in mitosis. Here the authors show that CIP2A–TOPBP1 coordinate mitotic DNA repair through the regulation of factors required for MiDAS and MMEJ.

This scenario study investigates how the EU net-zero target can be reached with varying levels of residual fossil fuels. Reducing fossils by only 90% relies on substantial carbon storage, while a full fossil phase-out requires a rapid scale-up of expensive carbon-neutral e-fuels.

Cancer immunotherapy benefits from antibody-lectin chimeras that block glyco-immune checkpoints.

Mirusviruses were detected in metagenomic datasets, but little is known about how they infect their hosts. Here, the authors characterize mirusviruses in the marine protist Aurantiochytrium, detecting virions, viral genes and proteins, and establishing this as a valuable model system.

Researchers use a chimeric approach to reveal the first near-atomic resolution structures the yellow fever virion, showing key differences between vaccine and virulent strains that affect how antibodies recognise and neutralise the virus.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

The BabyScreen+ study offered genomic screening to 1,000 newborns in Australia, and showed that the approach is feasible and positively received by families, leading to molecular diagnoses in 1.6% of babies.

A gene therapy method using AAV can help deliver HIV-fighting antibodies long-term, but the body often rejects them. Here the authors show that a short course of the drug rapamycin helps prevent host anti-drug antibody responses, showing successful antibody delivery in mice and monkeys.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Research on sustainable diets has primarily focused on human and planetary health, neglecting workers in food value chains. This study quantifies the risk of forced labour embedded in five different diets in the USA, underscoring the need to integrate such risk in sustainable diet transition efforts.

Cancer evolutionary dynamics are quantitatively inferred using a method, EVOFLUx, applied to fluctuating DNA methylation.

DNA2 suppresses recombination-restarted replication and checkpoint activation at stalled forks, and its loss triggers recombination-dependent synthesis, checkpoint signalling and cell-cycle exit, highlighting its essential role in proliferation and growth failure in primordial dwarfism.

The authors develop and characterise a selective Greatwall inhibitor, C-604, and show that its cytotoxicity stems from PP2A-B55α hyperactivation. They identify B55α and Greatwall levels as biomarkers of responses to Greatwall-targeted therapy.

Policies that centre principles of justice and human rights, specify inclusive decision-making processes and identify and challenge underlying drivers of injustice are linked to more just food system outcomes.

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.

Current treatment options for ovarian cancer are limited to surgery and chemotherapy, but most patients experience recurrent metastatic diseases. Here, the authors develop an antigen–adjuvant combination immunotherapy for ovarian cancer by coupling tumor antigen loaded liposomes with plant virus adjuvant as a vaccine platform to prevent cancer recurrence and metastatic diseases.

Monolayer semiconductors reveal their crystal quality and valleytronic properties in two-dimensional polarimetric imaging.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Withanolides are plant steroids with potent bioactivities found in many medicinal plants including Withania somnifera, but their biosynthetic pathway is largely unknown. Here, the authors report the genome assembly of W. somnifera and reveal a conserved gene cluster in Solanaceae plants for withanolide biosynthesis.

DNA ligase 1 finalizes nuclear DNA replication by accurately sealing nicks generated during Okazaki Fragment Maturation. Here, Williams et al employ a low fidelity DNA ligase 1 variant to study mutation rates and specificity across the yeast genome

This study presents 11 new hornwort (Anthocerotophyta) genomes that clarify the structure and evolution of sex and accessory chromosomes in bryophytes and shed new light on the early evolution of land plants.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Snaebjornsson et al. explore a selective vulnerability in cancer elicited by targeting aldolase A, which causes energy imbalance and prevents further metabolic adaptations.

Managing power exhaust in fusion reactors is a key challenge, especially in compact designs for cost-effective commercial energy. This study shows how alternative divertor configurations improve exhaust control, enhance stability, absorb transients and enable independent plasma regulation.

A microfluidic valve that amplifies the pressure in a fluid channel enables the realization of static microfluidic digital control logic. This in turn could enable more versatility and integration in the control of flows in ‘lab-on-a-chip’ systems.

On the anniversary of the Boyden et al. (2005) paper that introduced the use of channelrhodopsin in neurons, Nature Neuroscience asks selected members of the community to comment on the utility, impact and future of this important technique.

An oral inulin allergen gel restores the microbiota of allergic mice and suppresses undesired immune responses to achieve allergen-specific oral tolerance, effectively overcoming food allergy.

Externally applied electrical stimulation over the cervical spinal cord improves arm and hand functions in people with chronic tetraplegia due to spinal cord injury.

Conventional microscopy is unable to correlate nanoscale properties of metal halide perovskites with the performance of solar cells. Frohna et al. present a multimodal operando microscopy toolkit as a diagnostic tool to address the issue.

CD4⁺ T cells are known to be important in Plasmodium infection. Here the authors use mouse models to track antigen-experienced TCR transgenic and polyclonal CD4⁺ T cells during Plasmodium re-infection, and show different T cell phenotypes and varied responses in different areas of the spleen.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

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 arcuate fascicle connection with the middle temporal gyrus has been considered unique to humans. Using high-resolution diffusion MRI, the authors systematically show this connection in chimpanzees, suggesting a gradual evolution of the language network.

Meiotic cell division in oocytes is asymmetric and requires microtubule spindle migration after anaphase-onset. Here, the authors show that Nampt, an enzyme of the Nicotinamide adenine dinucleotide (NAD) biosynthetic pathway, contributes to post-anaphase spindle migration and oocyte division asymmetry by controlling spindle length.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

This manuscript evaluates forecasts of laboratory-confirmed influenza hospital admissions, a new target for influenza forecasting in the United States. Across two influenza seasons, the FluSight ensemble is robust compared to submitted models.

Medulloblastoma is one of the most prevalent malignant brain tumors in children and has very poor prognosis. In this study, the authors show, using a mouse model of medulloblastoma, that Gfi1 promotes tumor growth by recruiting Lsd1, that this interaction inhibits genes involved in neuronal differentiation, and that Lsd1 may be a therapeutic target in Gfi1-activated tumors.

Comparing infection routes and subsequent transmission of MPXV in the multimammate rat (Mastomys natalensis) indicates increased susceptibility, shedding and transmission via the genital mucosae.

Plant-parasitic nematodes have the potential to destroy crops globally, and limited options for managing nematode infestation are available. Here, the authors report the 1,3,4-oxadiazole thioether scaffold called Cyprocide that selectively kills nematodes including diverse species of plant-parasitic nematodes.

Light-driven approaches could lower the carbon footprint of chemical production. Here the authors use the perovskite oxide LaMn_1−xCu_xO₃ as a photocatalyst to convert ethane to ethylene and hydrogen.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Here, the authors demonstrate a wafer-scale, low-temperature process using atomic layer deposition, for the synthesis of uniform, conformal amorphous boron nitride (aBN) thin films. They further fabricate aBN-encapsulated monolayer MoS₂ field-effect transistors.

The gut microbiome can influence brain activity and complex behaviours. In this Review, Griffiths et al. discuss microbiome-associated effects on social behaviour in laboratory model organisms, free-living animals and humans, and consider potential mechanistic pathways.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.