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A common immune signature in the blood of patients with COVID-19, who are otherwise clinically heterogeneous, sheds light into the pathogenesis and clinical progression of the disease.

Analysis of 5hmC in tumor tissues and cfDNA reveals concordant cancer signatures that show potential for tissue origin prediction via liquid biopsy

Streptococcus pneumoniae is a common cause of lower respiratory tract infection. Here, Klabunde et al. present a transcriptomic, metabolomic and proteomic characterisation of the bronchial epithelial cell response to infection and show that NAD⁺ has a role in controlling bacterial replication.

Wireless sensing devices placed on the skin can capture a wide spectrum of acoustic and mechanical signals at several body locations simultaneously for monitoring of internal body processes such as cardiorespiratory function, gastrointestinal activity, swallowing and respiration.

Chini et al. demonstrate that CD38⁺ expression in immune cells increases during aging, owing to the senescence-associated secretory phenotype of senescent cells, and the ecto-enzymatic activity of CD38⁺ affects intracellular NAD⁺ levels in vivo by hydrolyzing the NAD⁺ intermediate nicotinamide mononucleotide extracellularly.

An extensive phylogenomics study based on hundreds of genomes and transcriptomes provides a new interpretation of the evolution of different types of symbiotic associations in land plants, and reveals a conserved ancestral symbiosis pathway.

The biology of Alzheimer’s disease (AD) remains unknown. We propose AD is a protein connectivity-based dysfunction disorder whereby a switch of the chaperome into epichaperomes rewires proteome-wide connectivity, leading to brain circuitry malfunction that can be corrected by novel therapeutics.

This study resolves a long-standing mystery of why t haplotypes, an example of selfish genes, have persisted at unexpectedly low frequencies in wild mouse populations. It shows that multiple mating by females, which is more common at higher mouse population densities, decreases the frequency of driving t haplotypes.

Circulating DNA detected in plasma can be used for diagnostic purposes. Here, the authors show that the 5-hydroxymethyl cytosine biomarker from plasma-derived cell free DNA can be used to detect early stage pancreatic cancer.

FLT3 is commonly mutated in acute myeloid leukaemia and treatment with FLT3 inhibitors often ends with relapse. Here, the authors perform exome sequencing of samples from patients treated with the FLT3 inhibitor, crenolanib, to show that resistance occurs due to diverse molecular mechanisms, not primarily due to secondary FLT3 mutations.

Anecdotal reports suggest potential severity and outcome differences between sexes following infection by SARS-CoV-2. Here, the authors perform meta-analyses of more than 3 million cases collected from global public data to demonstrate that male patients with COVID-19 are 3 times more likely to require intensive care, and have ~40% higher death rate.

Spatial control of auxin signaling maintains a balance between stem-cell self-renewal and differentiation at the plant shoot apex. Here Ma et al. show that rheostatic control of auxin response by the WUSCHEL transcription factor maintains stem cells by conferring resistance to auxin mediated differentiation.

The immunogen RC1 facilitates recognition of the V3-glycan patch on the envelope of HIV-1 and elicits specific serological responses in mice and macaques, making it a possible priming immunogen for sequential vaccination strategies in humans.

Long-term selective breeding has produced strains of the red fox (Vulpes vulpes) with different behaviours. Here, the authors sequence the genomes of tame and aggressive strains to uncover the genetic regions that have responded to selection for behaviour.

A procedure is established to image the entire human eye with light sheet fluorescence microscopy.

The kinase RAF1 usually exerts pro-tumorigenic functions promoting proliferation in RAS-driven cancers. Here, the authors using a mouse model of HCC and clinical data describe an unexpected oncosuppressor role of RAF1 in hepatocarcinoma development linked to a gp130-dependent Stat3 activation and YAP1 regulation.

CDKN2A loss and p53 mutations are rare in MYC-driven Group 3 medulloblastomas (MBs). Here the authors generated a transgenic mouse model of Group 3 MB by MYC overexpression and show that MYC suppresses ARF to drive tumorigenesis.

A phase I clinical trial of an adjuvant personalized mRNA neoantigen vaccine, autogene cevumeran, in patients with pancreatic ductal carcinoma demonstrates that the vaccine can induce T cell activity that may correlate with delayed recurrence of disease.

Exciton-polaritons present opportunities for quantum photonics, next generation qubits, and tuning material photophysics. Here Laitz et al. study the temperature dependence of 2D perovskite microcavity polaritons, revealing material-specific relaxation mechanisms towards the control of polariton momentum.

Knapp and colleagues show that elevated heme levels following hemolysis impair the control of bacterial proliferation by inhibiting phagocytosis and migration of human and mouse phagocytes independently of heme-iron acquisition by bacteria as a source of nutrients.

Human pluripotent stem cells with one copy of the BRCA2 gene deleted can be used to annotate variants of the gene and to test their sensitivities to inhibition by the poly(ADP-ribose) polymerase.

Single-cell profiling studies of the human gastrointestinal tract are increasing, offering an excellent opportunity to generate the first Human Gut Cell Atlas. This Roadmap presents a structured direction towards this goal and provides a detailed overview of the major challenges.

Cystinosis is a lysosomal storage disease that affects the kidney. Here, the authors use preclinical models and advanced profiling techniques to discover the mechanism by which defective cystine mobilization from lysosomes disrupts kidney cell function, offering insights into potential therapies.

Recognition memory for other individuals forms quickly. Here the authors show that such memories are enabled by oxytocin and can be retrieved from reinforced and more distinct neural representations even when only limited sensory information is available.

The evolution of non-recombining chromosomes is poorly understood. Here, the authors sequence the collared flycatcher female-specific W chromosome and show nonrandom survival of genes during W chromosome degeneration which is due to selection for maintaining gene dose and expression levels of essential genes.

The high expression of the DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT) often confers resistance to chemotherapy in several cancers. In this study, the authors propose the inhibition of the Wnt signalling pathway as an alternative strategy to modulate MGMT expression and sensitize tumours to chemotherapy.

The mesoSPIM is an open hardware axially scanned light-sheet microscope for the rapid imaging of large cleared samples with isotropic resolution.

Immune receptor FLS2 perceives flagellin epitopes from many bacterial pathogens, but not from well-known Agrobacterium tumefaciens. The authors find a natural FLS2 in a wild grape species that can perceive this modified flagellin.

Lasry and Nadorp et al. use single-cell RNA sequencing and CITE sequencing to reveal inflammatory gene expression in a subset of pediatric and adult patients with acute myeloid leukemia that associates with changes in the immune microenvironment and generate an inflammatory score with prognostic potential.

DeePiCt (deep picker in context) is a versatile, open-source deep-learning framework for supervised segmentation and localization of subcellular organelles and biomolecular complexes in cryo-electron tomography.

Neumüller and colleagues identify and characterize potent HER2 exon 20 insertion-selective inhibitors with efficacy, which preserve wild-type epidermal growth factor receptor signaling in preclinical models of non-small cell lung cancer in vivo.

Multiple alternative splicing events in CD19 mRNA have been associated with resistance/relapse to CD19 CAR-T therapy in patients with B cell malignancies. Here, by combining patient data and a high-throughput mutagenesis screen, the authors identify single point mutations and RNA-binding proteins that can control CD19 splicing and be associated with CD19 CAR-T therapy resistance.

Phosphorylation of the essential myosin light chain (ELC) influence actin-myosin crossbridge cycling in the heart. Here, the authors show upregulated ELC-phosphorylation in systolic heart failure and identify NIMArelated kinase 9 to bind to ELC mediating its calcium-dependent phosphorylation.

Dysregulation of the post-translational modification neddylation has been implicated in liver diseases such as fibrosis and hepatocellular carcinoma. Here the authors report that hepatic neddylation deficiency via genetic deletion of NEDD8 Activating Enzyme E1 Subunit 1 (NAE1) causes acute liver failure due to mitochondrial dysfunction and aberrant activation of NF-κB-inducing kinase in mice.

Gollwitzer et al. and Figlia et al. establish that the different Rag GTPase genes and isoforms differentially regulate mTORC1 activity and distinctly modulate the responsiveness of mammalian cells to amino acid availability.

A nanoscale rotary motor made of DNA origami, driven by ratcheting and powered by an external electric field, shows the ability to wind up a spring and has mechanical capabilities approaching those of biological motors.

Changes in glycoprotein expression are correlates of disease, but secreted glycoproteins cannot be accurately traced to their cell line of origin. Here, the authors develop a strategy to chemically tag and profile glycoproteins in a cell line-specific manner in co-culture systems and in vivo.

A repeating fast radio burst co-located with a persistent radio source and associated with a dwarf host galaxy of a high star-formation rate has been detected.

An isolated butterfly population that became dependent on a plant introduced to their habitat by cattle ranchers went extinct after the plant’s dominance decreased.

Machine learning tools are used to greatly accelerate chip layout design, by posing chip floorplanning as a reinforcement learning problem and using neural networks to generate high-performance chip layouts.

Permafrost peatlands are thawing, yet the timing and spatial dynamics of thaw are not well constrained. Under moderate and high warming scenarios, permafrost peatlands in Europe and Western Siberia will cross a tipping point where the climate becomes unsuitable, putting their carbon stores at risk.

Heterologous expression of recombinant proteins often results in misfolding, aggregation and degradation. Here, we show an in vivo dual-biosensor system that simultaneously assesses protein translation and protein folding, thereby enabling rapid screening of expression strains as well as mutant libraries.

The hippocampus is known to 'replay' experiences and memories during rest periods, but it is unclear how particular memories are prioritized for replay. Here, the authors show that information that is remembered less well is replayed more often, suggesting that weaker memories are selected for replay.

Single-species antibiotic dose response is a poor predictor of multi-species community dynamics because it cannot foresee the tipping points that cause irreversible changes in resistance that persist even when treatment stops.

Chinese government has implemented regulations to reduce mining-related methane emission since 2010. Here the authors estimated methane emissions in China using GOSAT satellite observation and results reveal a business-as-usual increase in methane emissions since 2010 despite those ambitious targets.

Analysis of evolutionary dynamics of colorectal cancers and paired distant brain or liver metastases provides evidence that early disseminated cancer cells seed metastases before the carcinoma is clinically detectable.