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Structural classification of mutations in the epidermal growth factor receptor causing non-small cell lung cancer is a better predictor of patient outcomes following drug treatment than traditional exon-based classification.

Analysing camera-trap data of 163 mammal species before and after the onset of COVID-19 lockdowns, the authors show that responses to human activity are dependent on the degree to which the landscape is modified by humans, with carnivores being especially sensitive.

High-fidelity convergent total synthesis is used to produce Escherichia coli with a 61-codon synthetic genome that uses 59 codons to encode all of the canonical amino acids.

Drp1 is the master regulator of mitochondrial and peroxisomal fission. Here, the authors show that a C-terminal intrinsically disordered motif, named the CT-SLiM, constitutes an allosteric switch that controls Drp1 structure, assembly, and function.

The contribution of oligodendrocytes to remyelination in functional recovery after spinal cord injury is not fully understood. Here, the authors show that oligodendrocyte progenitor cell differentiation is not required for functional recovery after spinal cord injury in mice.

Korobkina et al. show that ACLY in brown fat prevents metabolic overload in the tricarboxylic acid cycle, thus ensuring adequate thermogenesis by avoiding cellular stress.

Trapped in rock fractures miles below the surface are saline waters that have been isolated for millions of years. In these most remote environments exists an active turnover of dissolved organic molecules, an active carbon cycle.

Holo-acyl carrier protein synthase (AcpS) is an enzyme that catalyses the first step in lipid synthesis and is essential for bacterial survival, but no current antibiotics targeting AcpS are known. Here, the authors use computer-aided drug design to develop a structurally unique antibiotic family targeting AcpS.

A report from the Australian Acute Care Genomics programme shows that the integration of rapid whole-genome sequencing and multi-omic analyses informs diagnoses and treatment decisions in a prospective cohort of 290 critically ill infants and children.

Rifaximin use, particularly in patients with liver cirrhosis, may be compromising the clinical use of daptomycin.

Plastic reweighting of parallel fiber synaptic strength is a mechanism for the acquisition of cerebellum-dependent motor learning. Here, the authors found that optogenetic activation of PCs generates dendritic Ca2+ signals that induce plasticity in vitro and instruct learned changes to coincident eye movements in vivo.

Seven leading geneticists express their views about where the unidentified components of the heritability for complex human diseases might lie and how this could affect the underlying genetic architecture, as well as offering suggestions of how genomic research could be targeted to address this key issue.

Time-resolved crystallography (TRX) is used for monitoring only small conformational changes of biomacromolecules within the same lattice. Here, the authors report the interplay between synchronous molecular rearrangements and lattice phase transitions in RNA crystals, providing the basis for the investigation of large conformational changes using TRX.

UBE3A gene dysregulation is associated with neurodevelopmental disorders, but predicting the function of UBE3A variants remains difficult. The authors use a high-throughput assay to categorize variants by functional activity, and show that UBE3A hyperactivity increases the risk of neurodevelopmental disease.

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.

Salisbury et al. show that hepatic lipogenic mRNA is regulated by m⁶A modifications in a sex-dependent and dietary-dependent manner, contributing to sex-specific differences in hepatic lipid metabolism.

Unlike Amazonian forests, African forests have maintained their carbon sink until recently but by 2030 the African carbon sink will have shrunk by 14 per cent and the Amazonian sink will reach almost zero.

The molecular basis underlying infection infection-mediated lung pathology is not fully revealed. Here the authors report that SPARCL1 expressed in pulmonary capillary endothelial cells contributes to immune pathology in mouse model via pro-inflammatory macrophage induction, while circulating SPARCL1 levels corelate with COVID-19 lethality.

Genome-wide comparative analysis of DNA binding for 200 transcription factors in two maize inbred lines reveals prevalent genotype-specific variation that is associated with gene expression differences and agronomic traits.

Inflammatory bowel diseases (IBD) are associated with increased faecal N-acylethanolamines (NAEs), which are primarily host-produced signalling lipids, in patients and a mouse model of colitis. These metabolites can enhance the growth of bacterial species enriched in IBD faecal samples and are associated with the expression of respiratory chain genes necessary for microbial metabolism of NAEs.

The molecular determinants of differential responses of different cancer cells to methionine restriction are poorly understood. Here the authors show that hepatocyte nuclear factor 4α regulates sulfur amino acid metabolism and dictates the sensitivity of liver cancer to this dietary manipulation.

Neuronal development is tightly controlled by nutrients and antioxidants. Here, authors show that ferroptosis, a cell death modality driven by lipid peroxidation, is required to be suppressed by vitamin A or antioxidants to ensure proper neuronal development.

Here the authors describe a 3D genomic strategy that uncovers novel enhancer hijacking events, including a MYC-ERBB2 chimeric ecDNA, providing new insights into oncogene activation and potential therapeutic targets.

A screen for compounds that alter fat content in C. elegans identifies a novel agonist of an AMP-activated kinase pathway that reduces fat storage as well as implicates the transcription factor K08F8.2 as a regulator of fat metabolism.

Federated learning (FL) has emerged as a potential solution to train machine learning models in multiple clinical datasets while preserving patient privacy. Here, the authors develop an MRI-based FL platform for pediatric posterior fossa brain tumors—FL-PedBrain—and evaluate it on a diverse multi-center cohort.

Analysing the regulatory consequences of mutations and splice variants at large scale in cancer requires efficient computational tools. Here, the authors develop RegTools, a software package that can identify splice-associated variants from large-scale genomics and transcriptomics data with efficiency and flexibility.

Over half the world’s rivers dry periodically, yet little is known about the biological communities in dry riverbeds. This study examines biodiversity across 84 non-perennial rivers in 19 countries using DNA metabarcoding. It finds that nutrient availability, climate and biotic interactions influence the biodiversity of these dry environments.

Progressive diseases tend to be heterogeneous in their underlying aetiology mechanism, disease manifestation, and disease time course. Here, Young and colleagues devise a computational method to account for both phenotypic heterogeneity and temporal heterogeneity, and demonstrate it using two neurodegenerative disease cohorts.

GWAS have identified risk loci for osteoarthritis (OA), but the causal variants still have to be determined. Here, the authors apply a massively-parallel reporter assay to screen 1,605 candidate SNPs in 35 OA loci, which prioritizes six SNPs in four loci, one of which, rs4730222, is characterized in more detail.

Koh et al. show that loci active in differentiated effector T cells are poised in early T precursors before the expression of T cell antigen receptors in a manner dependent on the chromatin remodeling complex mammalian SWItch/Sucrose Non-Fermentable and the PU.1–RUNX1 and BCL11B–RUNX1 complexes.

Extracellular microinterfaces provide cells with migration tracks in vivo. Here, the authors introduce these microtracks into bicontinuous hydrogels to elicit rapid cell migration in 3-dimensional contexts.

Foliar application of different forms of nanoscale copper to plant seedlings induces material-specific biochemical and molecular changes in root tissue that stimulate plant defence against soybean sudden death syndrome.

Trials in rhesus macaques show that a subunit vaccine against SARS-CoV-2, comprising the spike protein receptor-binding domain displayed on a nanoparticle protein scaffold, produces a robust protective response against the virus.

Nanoparticle-based ‘microgauges’ are developed for in vivo force sensing and deployed in C. elegans to investigate how mechanical force correlates with electrical signalling in neuromuscular organs.

Genetics implicate microglia in Alzheimer’s disease pathogenesis, but their roles remain unclear. Here, the authors find that microglial depletion in a mouse model of Alzheimer’s disease impairs plaque formation and that Aβ-induced changes in neuronal gene expression are microglia-mediated.

Gammaherpesviruses are DNA viruses that result in lifelong latent infections. Here Owens and colleagues show that intrinsic activation of p53 restricts gammaherpesvirus-linked germinal centre B cell expansion during the establishment of latency in a murine model.

A multifaceted approach was used to shed light on the genetic factors behind the heterogeneity that is observed in vitro and in vivo in the colony morphology of Aspergillus fumigatus isolates and on the impact of such morphological variation on fungal fitness and pathogenesis.

Elucidation of the mechanism by which zeta inhibitory peptide erases memories, involving endocytosis of AMPA receptors on potentiated synapses, provides insight into more general mechanisms of memory maintenance and response to traumatic brain injury.

Coastal ecosystems are sensitive to changes in the quantity and lability of terrigenous dissolved organic matter (DOM) delivered by rivers. The lability of DOM is thought to decrease with age, but this view stems from work in watersheds where terrestrial plant and soil sources dominate streamwater DOM. Here, glaciated watersheds on the Gulf of Alaska are shown to be a source of old but labile dissolved organic matter, suggesting that glacial runoff is an important source of labile reduced carbon to marine ecosystems.

C−H bond functionalization methodologies usually rely on substrate-controlled directing-group chemistries to facilitate regioselective activation. Now, chemobiocatalytic cascades are reported that enable catalyst-controlled regioselective access to aryl nitriles, primary amides and carboxylic acids.

A bulky residue in the stem domain of the influenza virus H2 hemagglutinin appears pivotal in eliciting broadly cross-reactive antibodies capable of recognizing diverse group 1 influenza subtypes and is informative for universal influenza vaccine development.

When an extrasolar planet passes in front of its star (transits), its radius can be measured from the decrease in starlight and its orbital period from the time between transits. This study reports Kepler spacecraft observations of a single Sun-like star that reveal six transiting planets, five with orbital periods between 10 and 47 days plus a sixth one with a longer period. The five inner planets are among the smallest for which mass and size have both been measured, and these measurements imply substantial envelopes of light gases.

This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the molecular basis of human disease.

Kyle Gaulton, Mark McCarthy, Andrew Morris and colleagues report fine mapping and genomic annotation of 39 established type 2 diabetes susceptibility loci. They find that the set of potential causal variants is enriched for overlap with FOXA2 binding sites in human islet and liver cells, and they show that a likely causal variant near MTNR1B increases FOXA2-bound enhancer activity, providing a molecular mechanism to explain the effect of this locus on disease risk.

EBV (Epstein-Barr virus)-targeted therapy is limited by efficient agents inducing lytic cycle in cancer cells. Here they report a transcriptional activator incorporated into lipid nanoparticles that could specifically activate endogenous BZLF1 and induce lytic reactivation in EBV-positive cancer cells thereby suppress tumor progression.

Current guidelines recommend stereotactic radiosurgery for brain metastasis measuring less than 3 cm but there is significant variability in outcomes following treatment. This study shows that in treatment naïve brain metastasis less than 3 cm, intrinsic biological differences across multiple histologies may influence response to stereotactic radiosurgery.

Phytoplankton are important primary producers. Here the authors investigate phytoplankton physiological changes associated with bloom phases and mixing regimes in the North Atlantic, finding that stratification and deep mixing shape accumulation rates by altering physiology and viral production.