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MitoCatch is a cell-type-specific mitochondrion-targeting system that links mitochondria and the cell surface by protein binders and delivers mitochondria into the target cell.

Greying with age in horses is caused by an intronic copy number variation in the Syntaxin 17 gene. Here the authors report that the G2 allele with two copies of the duplicated sequence causes slow greying whereas G3 with three copies causes fast greying and a high risk of melanoma.

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.

In-flight observations show that the use of lean-burn combustion succeeds in reducing soot emissions from aircraft—yet contrail ice crystals still form and nucleate on volatile particles.

The predicted increase in frequency of droughts and rising temperatures in Europe will lead core populations of a temperate plant to an evolutionary dead-end unless they acquire genetic alleles that are present only in extreme edge Mediterranean, Scandinavian, or Siberian populations.

Here, the authors leverage stable isotope and peptide analyses to show that some 18th century Māori individuals ate largely plant-based diets. This work aligns with Māori oral history and archaeological evidence, which points to sweet potato and taro cultivation as important for population growth and cultural change at the time.

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.

Longitudinal metatranscriptomics in a prospective cohort of 1,164 adults hospitalized for COVID-19 reveals that azithromycin offered no apparent anti-inflammatory benefit but enriched the respiratory microbiome with potential pathogens and antimicrobial resistance genes.

Twenty years after UK Biobank was established, the incidence of dementia among participants is set to rise rapidly. In this Perspective, Matthews et al. highlight how UK Biobank has advanced dementia research in its first 20 years and consider how future developments will leverage increasing incidence to further advance understanding of dementias.

Here the authors present a compendium of avirulence genotypes for epidemiologically significant strains of wheat stem rust based on nuclear phased genome assemblies and functional assays to inform resistance gene deployment and pathogen surveillance.

Biallelic variants in RNU4-2 cause a recessive neurodevelopmental disorder that is phenotypically and molecularly distinct from dominant ReNU syndrome and associated with reduced RNU4-2 transcript levels, consistent with a loss-of-function mechanism.

Individual supratentorial ependymoma tumour subgroups have two distinct progenitor-like cell states—neuroepithelial-like and embryonic-like—that are reminiscent of early human brain development and diverge in the extent of their neuronal or ependymal differentiation.

Analysis of sequencing data from rare disease cohorts identifies biallelic variants in RNU2-2 underlying a developmental and epileptic encephalopathy associated with reduced U2-2 abundance and clinically distinct from the dominant RNU2-2 disorder.

As soft electronic waste becomes an urgent concern, biodegradable yet high-performance devices are emerging as a promising solution. Here the authors fabricate durable and multifunctional soft robotic fingers in which both polymers and inorganic electronics are fully compostable.

Navigational affordances describe our ability to identify routes of egress within scenes. Here, the authors show that this process likely occurs in early dorsal visual cortex and that such navigational affordances can emerge following brief presentation times.

Three BRAF inhibitors are used to treat melanoma and colorectal cancer. Here, the authors demonstrate that these drugs bind and activate the protein kinase GCN2, a previously unappreciated off-target effect that may modulate tumour cell responses.

The planum temporale is a key structure in the human language network. Here the authors show that planum temporale asymmetry at birth in baboons predicts the development of communicative right-hand use, which suggests some common features in the wiring of communicative properties between species.

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.

A platform using matched patient-derived lung tumouroids and healthy lung organoids enables accurate examination of patient responses to CAR T therapy and offers a faithful framework for improved CAR T design.

Reconstructing microbial genomes from 820 reef-building corals collected at 99 reefs across 32 islands throughout the Pacific Ocean highlights the importance of conserving coral reefs as vital reservoirs of molecular diversity.

Population-level distributions of SARS-CoV-2 viral load can correlate with epidemic trends. Here, the authors use viral loads to nowcast epidemic growth rates over two-week periods and investigate how the relationship varies by peak viral load, viral dynamics, and sampling approaches.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

T-cell acute lymphoblastic leukemia is a highly aggressive disease with varying recurrence rates. Here, the authors build a single cell transcriptomic atlas of childhood T-cell acute lymphoblastic leukaemia (T-ALL). They identified a distinctive cancer cell state that correlates with high risk, treatment refractory T-ALL.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

The authors provide an interactive resource of folate one-carbon metabolism in 37 tissues in germ-free and conventional mice.

Deep learning methods have been used to design proteins that can neutralize the effects of three-finger toxins found in snake venom, which could lead to the development of safer and more accessible antivenom treatments.

Graber et al. characterize biases and data leakage in protein–ligand datasets and show that a cleanly filtered training–test split leads to improved generalization in binding affinity prediction tasks.

The authors optimize an in vitro human epiblast model, which they utilize to show that early TGFβ family inhibition prevents epithelial identity, whereas it is dispensable after epithelium formation. These phenomena are conserved in mice.

An optical detection and analysis platform quantifies aggregate density, distribution and size in fluorescently labelled post-mortem human brain tissue.

In this study, the authors develop a flavivirus vaccine strategy by introducing mutations into envelope glycoproteins resulting in structural changes that conceal the ADE-prone fusion loop epitope. They show that the Zika virus-specific construct protects mice against viral challenge and prevents ADE by Dengue virus.

Using a non-human primate model, the authors identified the tissue sites of initial viral rebound after discontinuation of antiretroviral therapy, demonstrating that such rebound preferentially occurs in the gastrointestinal tract-associated lymphoid tissues.

Pulsed electron-electron double resonance spectroscopy (PELDOR/DEER) and single-molecule Förster resonance energy transfer spectroscopy (smFRET) are used to determine conformational changes and probe distances in biological macromolecules. Here the authors compare the methods on a large set of samples.

Controlling nanoscale colloidal crystallization is not straightforward. Such control is now achieved by leveraging a metastable liquid phase of charged nanocrystals.

A flavin-dependent halogenase with a remarkable preference for iodination has now been discovered. The halogenase (VirX1) was discovered using a bioinformatics-based approach and comes from a cyanophage. Structural characterization and kinetic studies show that VirX1 possesses broad substrate tolerance, making it an attractive tool for synthesis.

Protein citrullination is linked to autoimmunity and inflammation but is challenging to detect globally. Here, the authors report a high-throughput chemical proteomics workflow and demonstrate its utility by quantifying the dynamic citrullinome in human neutrophils.

Cryptococcal meningitis is a common infection in patients with compromised CD4 T cell function. Using a CD4 T cell activation tracking mouse the authors show the localisation and activation of CD4 T cells in the brain after cryptococcus infection and how these cells interact with MHCII expressing microglia which may increase pathologic brain inflammation.

A systematic review including 574 studies extracts information about transmissibility, epidemiological delays and outbreaks for Zika virus disease at global scale.

RH5, which is part of the trimeric RCR-complex essential for invasion, is a vaccine candidate for malaria. Here, Williams et al. show that monoclonal antibodies targeting each of the three proteins in the RCR-complex can work together to more effectively block the invasion of red blood cells by Plasmodium falciparum and design a combination vaccine candidate.

Factors limiting CNS remyelination with age are poorly understood. Here the authors show that aged Treg lose capacity to support CNS remyelination in mice, which can be restored in a young environment.

The neuronal architecture that develops after spinal cord injury and causes autonomic dysreflexia is uncovered.

Together with a companion paper, the generation of a transcriptomic atlas for the mouse lemur and analyses of example cell types establish this animal as a molecularly tractable primate model organism.

Inhibiting insulin-degrading enzyme (IDE) has been proposed as a potential therapeutic strategy for the treatment of patients with diabetes. Here, the authors develop a novel IDE inhibitor but find that, surprisingly, IDE inhibition has negative effects on glucose tolerance in mice.

Radiation reaction (RR) on particles in strong fields is the subject of intense experimental research, but previous efforts lacked statistical significance due to the extreme regimes required. Here, the authors report a 5σ observation of RR and obtain strong, quantitative evidence favouring quantum models over classical, using an all-optical setup where electrons are accelerated by a laser in a gas jet before colliding with a second, intense pulse.

Data collected from more than 2,000 taxa provide an unparalleled opportunity to quantify how extreme wildfires affect biodiversity, revealing that the largest effects on plants and animals were in areas with frequent or recent past fires and within extensively burnt areas.

A single-cell resolution image-based genome-wide CRISPR screen, analysed with deep learning and random forest models, identified host factors regulating Ebola virus infection at distinct stages in the viral life cycle.

GATA2 deficiency is one of the major causes of hereditary pediatric myelodysplastic neoplasms (MDS). Using iPSC-based models, this work recapitulates stepwise mutational trajectories in GATA2-related MDS and reveals their impact on myeloid differentiation.