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ER membranes tune protein degradation to lipid composition. Using reconstitution approaches, the authors show that the ubiquitin conjugating enzyme UBE2J2 senses lipid packing, modulating its own and partner enzyme activities; together, they integrate lipid saturation and cholesterol signals.

How the brain integrates sensory input and predictions to adapt to change is not fully understood. Here authors build a neural network model to show how prediction-error neurons compute uncertainty of sensory signals & predictions, revealing mechanisms behind adaptive behavior.

Long-term effects of fetal SSRI exposure—commonly prescribed to pregnant mothers who suffer from depression and anxiety—are unknown. Here, authors finds increased fear-related behaviors and matching brain circuit activation in both mice and humans.

The molecular characteristics and therapeutic vulnerabilities of TFCP2-rearranged rhabdomyosarcomas (RMS) require further exploration. Here, the authors use multi-omics analyses and functional and mechanistic investigations to characterize TFCP2-rearranged RMS – including cases with FUS/EWSR1-TFCP2 fusions – across two precision oncology programs.

Here, using ex-vivo human adult cortical tissue and a mouse model, the authors investigate the functional consequences of Zika virus (ZIKV) infection in the adult brain, and show that ZIKV causes synapse damage and altered brain function that impacts cognition via activation of innate and inflammatory factors.

A study identifies a new bacterial ribosome hibernation factor, Balon, and describes its association with EF-Tu and its initiation of mRNA-independent hibernation during protein synthesis.

Derailed differentiation of human-specific progenitors of the developing cerebellar rhombic lip is the cause of group 4 medulloblastoma, the most common childhood brain tumour. 

A multi-ancestry genome-wide association meta-analysis of kidney cancer identifies 63 regions associated with disease susceptibility including one locus that was associated with increased risk in individuals with African ancestry.

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.

Single-cell and spatial transcriptomic analysis of eight human heart tissues reveals the cellular profiles and tissue architecture of niches including the cardiac conduction system, and a new tool, drug2cell, identifies drug target expression.

A global field survey of 383 sites with different vegetation types spanning an environmental gradient reveals that soil biodiversity and functions exhibit pervasive nonlinear behaviours worldwide and are mainly governed by water availability.

Neural population activity in the medial entorhinal cortex of mice can be organized into ultraslow oscillatory sequences, with periods extending up to the minute range.

The potent antibacterial compound albicidin is synthesized by the plant-pathogenic bacterium Xanthomonas albilineans. Here the authors employ a multidisciplinary approach and provide structural and mechanistic insights into how the drug-binding protein AlbA confers albicidin resistance to Klebsiella oxytoca.

The surfactant-like protein Ki-67 mediates the clustering of chromosomes during mitotic exit, which displaces large cytoplasmic molecules from the future nuclear space and thus enables the separation of cytoplasmic and nuclear components before the nuclear envelope reforms.

This study shows that a subpopulation of astrocytes in the central amygdala (CeA) expresses the oxytocin receptor (OTR) and that OTR activation in astrocytes underlies the anxiolytic and positive reinforcement effects of oxytocin in the CeA.

Super-resolution microscopy demonstrates how changes in the 3D organization of chromatin protect DNA against excessive degradation following damage.

An epidural spinal cord stimulation system regulates blood pressure in the acute and chronic phases of spinal cord injury.

The underlying mechanisms structuring dissolved organic matter (DOM) composition and reactivity in rivers remain poorly quantified. Here, the authors pair mass spectrometry and fluorescence spectroscopy to show that hydrology and river geomorphology both shape molecular patterns in DOM composition.

Optogenetics is applied to the entire mouse spinal cord.

γδ T cells are known to recognize phosphoantigen in the context of butyrophilins (BTN), yet the molecular rules underlying this phenomenon are unclear. Here, the authors demonstrate that a distinct topology of B30.2 and IgV domains within BTN3A complexes promotes antigen sensing and that the juxtamembrane region controls BTN complex formation.

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.

Histone deacetylation at the onset of mitosis induces a chromatin-intrinsic phase transition that endows chromosomes with the physical characteristics necessary for their precise movement during cell division.

An ab initio study suggests that a known oxide superconductor, BaBiO₃, can be doped into a topological insulating state. This would simplify topological insulator–superconductor structures for applications.

Input decorrelation, expansion recoding and sparse activity have been proposed to separate overlapping activity patterns in feedforward networks. Here the authors use reduced and detailed spiking models to elucidate how synaptic connectivity affects the contribution of these mechanisms to pattern separation in cerebellar cortex.

Cytosolic ion gradients in growing pollen tubes are thought to be required for polar growth. Here the authors show that the Arabidopsis plasma membrane H⁺ ATPases, AHA6, AHA8, and AHA9, maintain tip-to-shank proton gradients, oscillations in cytosolic pH and actin organization to enable pollen tube elongation.

The synthesis of atomically precise gold nanoclusters is highly desired for fundamental studies and applications. Here, the authors report the formation of a superfluorinated gold nanocluster stabilized by a multi-branched highly fluorinated thiol ligand, and characterize its crystal structure and molecule-like spectroscopic properties.

Human behaviour is complex and multifaceted, and is studied by a broad range of disciplines across the social and natural sciences. To mark our 5th anniversary, we asked leading scientists in some of the key disciplines that we cover to share their vision of the future of research in their disciplines. Our contributors underscore how important it is to broaden the scope of their disciplines to increase ecological validity and diversity of representation, in order to address pressing societal challenges that range from new technologies, modes of interaction and sociopolitical upheaval to disease, poverty, hunger, inequality and climate change. Taken together, these contributions highlight how achieving progress in each discipline will require incorporating insights and methods from others, breaking down disciplinary silos.

Activating mutations in the Wnt signalling pathway are associated with colon cancer. Here the authors show that tumour cells carrying mutations in APC and β-catenin are still regulated by Wnt ligands, suggesting that Wnt secretion and receptor signalling remains important to control downstream signalling.

The canonical DNA methylation maintenance enzyme Dnmt1 displays global de novo methylation activity with greater targeting towards IAP transposons, which may contribute to their stable repression during early development.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

The discovery of an alternative squalene epoxidase (AltSQE) belonging to the fatty acid hydroxylase superfamily in the diatom Phaeodactylum tricornutum and other eukaryotic lineages solves the mystery of the existence of a steroid biosynthesis pathway in eukaryotes that lack the canonical flavoprotein SQE.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

The tumour suppressor complex BRCA1–BARD1, which facilitates the generation of a single-stranded DNA template during homologous recombination, also binds to the recombinase RAD51 and enhances its function.

How neural stem cells can transition between states of proliferation and quiescence is unclear. Here, the authors identify Lrig1 as a specific marker for the primed quiescent state and demonstrate that Lrig1 maintains cells in a quiescent state via modulation of the EGFR pathway.

Biochemical and biophysical analyses of eye lenses from mouse strains that develop cataract due to mutations in α-, β-, or γ-crystallin proteins reveal that the mutant protein levels are largely reduced, but other crystallin proteins, including α-crystallins, precipitate.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Hanno Glimm, Jan Korbel and colleagues present a computational framework called cis expression structural alteration mapping (CESAM), which they use to identify somatic copy-number alterations affecting cis-regulatory elements in cancer. They find that enhancer hijacking leads to overexpression of IRS4 and IGF2 in cancer.

A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.