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Semaphorin 5A (Sema5A) forms complexes with heparan and chondroitin sulfate proteoglycans to regulate neuronal migration. Here, the authors show that the thrombospondin-like repeat 4 (TSR4) of Sema5A enables glycosaminoglycan association, multimerization, and neural progenitor cell distribution.

Checking the quality of operations of quantum computers in a reliable and scalable way is still an open challenge. Here, the authors show how to characterise multi-qubit operations in a way that scales favourably with the system’s size, and demonstrate it on a 10-qubit ion-trap device.

Transmission spectroscopy observations from the James Webb Space Telescope show the detection of carbon dioxide in the atmosphere of the gas giant exoplanet WASP-39b.

Metabolism can influence gene expression through histone modifications. Using a mouse model of the inborn error of metabolism propionic acidaemia, Park et al. show how raised propionate levels produce epigenetic actions that impact cardiac function.

Coronary artery calcium is an accurate predictor of cardiovascular events but this information is not routinely quantified. Here the authors show a robust and time-efficient deep learning system to automatically quantify coronary calcium on CT scans and predict cardiovascular events in a large, multicentre study.

In semiconductors, accessing nonlinear interactions between excitons strongly coupled to light will be key for quantum technologies. Here, in atomic bilayers of MoS₂, new types of excitons are discovered showing strong inter-excitonic interactions.

Assisted migration is the artificial movement of species and populations to increase forest resilience. Here the authors model how targeted assisted migration can preserve or enhance the European forest carbon sink under future climate scenarios.

Genome-wide ancient DNA data from 225 individuals who lived in southeastern Europe between 12000 and 500 bc reveals that the region acted as a genetic crossroads before and after the arrival of farming.

Protein-protein interactions (PPIs) are crucial for biological functions and have applications ranging from drug design to synthetic cell circuits. Here the authors develop an assay and computational methods to identify more orthogonal coiled-coil pairs, critical for biological processes and drug design.

Thomas Bugge and colleagues report that the matriptase protease initiates an epidermal kallikrein proteolytic cascade in mice lacking Spink5, which encodes the serine protease inhibitor LEKTI. Loss of matriptase rescued some features of excessive proteolytic degradation of corneodesmosomes and inflammatory activation in LEKTI-deficient mice, which are a model of human Netherton syndrome.

Neoantigen prediction from clinical samples is improved using a neural network model trained on a large HLA peptide and genomic tumor dataset.

Nucleocytoplasmic Large DNA Viruses (NCLDV) that infect algae encode two distinct families of microbial rhodopsins. Here, the authors characterise two proteins form the viral rhodopsin group 1 OLPVR1 and VirChR1, present the 1.4 Å crystal structure of OLPVR1 and show that viral rhodopsins 1 are light-gated cation channels.

Germany is paving the way toward genomics-based personalized healthcare and translational research.

Characterizing surfaces by Raman spectroscopy is limited by the competition of surface and bulk Raman responses. Here the authors use nanoporous plasmonic membranes to enhance surface Raman signals while suppressing bulk contributions.

Hodgkin's lymphoma has become a curable disease successfully treated using dose-escalated BEACOPP chemotherapy regimens pioneered by the German Hodgkin's Lymphoma Study Group. However, the unacceptable side effects of chemotherapy have propagated new therapeutic concepts based on biological characteristics of the disease to be explored. This viewpoint discusses the promises and pitfalls of targeted therapy.

Reforestation has been recently identified as a promising climate mitigation option. In Southeast Asia, 120 million ha of land are biophysically suitable for reforestation. However, financial, land-use and operational factors constrain mitigation potential to a fraction of its total possible value.

The authors discovered that proinflammatory senescent myeloid cells may recruit peripheral immune cells in the aged mouse brain. Their findings implicate senescent cell clearance as a strategy to counter aged brain inflammation and cognitive decline.

Current approaches possibly cannot unambiguously distinguish the unique contributions of feedback inhibition versus feedforward inhibition to oscillatory events. Here authors show that a loss of CA1 pyramidal cell transmission, resulting in feedback inhibition reduction, leads to spatially triggered high-frequency oscillatory events; these events were like place cells in their spatial extent and localized to small regions in CA1.

Analyses of the proportions of individuals who have completed key levels of schooling across all low- and middle-income countries from 2000 to 2017 reveal inequalities across countries as well as within populations.

Morphogen gradients encode positional information during development. Here the authors use theory and simulations to suggest a positional accuracy of single gradients that directly explains the observed precision of progenitor domain boundaries.

The first lasing results at SwissFEL, an X-ray free-electron laser, are presented, highlighting the facility’s unique capabilities. A general comparison to other major facilities is also provided.

Synthesis of atomically precise zigzag edges in graphene nanoribbons is demonstrated using a bottom-up strategy based on surface-assisted arrangement and reaction of precursor monomers; these nanoribbons have edge-localized states with large energy splittings.

Comprehensive analyses of 178 lung squamous cell carcinomas by The Cancer Genome Atlas project show that the tumour type is characterized by complex genomic alterations, with statistically recurrent mutations in 11 genes, including TP53 in nearly all samples; a potential therapeutic target is identified in most of the samples studied.

The expression of oncogenic MYC paralogs in small cell lung cancer is mutually exclusive. In this study, the authors show that MYC, but not MYCN or MYCL, represses BCL2, resulting in cells that are uniquely sensitive to apoptosis, and find that CHK1 and AURKA inhibitors may be useful for treating these cancers.

The CTLA-4–Ig fusion protein (abatacept) can have beneficial effects in autoimmune disease. Walker and colleagues show in mouse and human type 1 diabetes that abatacept targets pathogenic follicular helper T cells, and the frequencies of these cells at baseline can be used to stratify treatment responses in patients.

Rhodopsin genes have been identified in some large double-stranded DNA viruses, but the structure and functions of viral rhodopsins remain unknown. Here authors present crystal structure and characterization of an Organic Lake Phycodnavirus rhodopsin II (OLPVRII) which forms a pentamer and is a weak proton pump.

Two-photon calcium imaging reveals that the mouse retina contains more than 30 functionally distinct retinal ganglion cells, including some that have not been described before, exceeding current estimates and suggesting that the functional diversity of retinal ganglion cells may be much larger than previously thought.

The molecular nature of large-cell neuroendocrine lung carcinomas (LCNEC) has remained unclear. Here, the authors show LCNECs represent a distinct transcriptional subgroup among lung cancers and comprise two molecular subgroups, type I (TP53 and STK11/KEAP1 alterations) and type II (TP53 and RB1 inactivation).

Small-cell lung cancer (SCLC) is an aggressive disease with limited therapeutic options. Here the authors perform an immunogenomic analysis of limited-stage SCLC, revealing a homogeneous mutational landscape, but limited T-cell infiltration and a cold and heterogeneous T cell repertoire.

Building crystal structures into the electron density is an important step in protein structure solution. Here, the authors recruit online game players, students, and experienced crystallographers to compete in a competition to solve a new structure, and find that crowdsourcing model-building works.

Ji and colleagues demonstrate that metabolic reprogramming in SCLC underlies chemotherapy resistance, resulting in an actionable dependency on the mevalonate pathway in tumor cells, which can be targeted using statins to revert chemoresistance.

A genomic analysis of ductal carcinoma in situ (DCIS) samples with matched ipsilateral invasive breast cancer recurring later shows that around 18% of tumors were unrelated to the DCIS, and had distinct clonal origins.

AtEH/Pan1 proteins contain two N-terminal Eps15 homology (EH) domains and are subunits of the endocytic TPLATE complex present in plants. Here, the authors combine X-ray crystallography, NMR and MD simulations with biochemical and in planta analysis to characterize the two AtEH1/Pan1 EH domains and reveal their structural differences and complementary functional roles.

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.

Mirrors that demonstrate 98% reflectivity and withstand 10 kilowatts of focused continuous-wave laser light are created by nanoscale fabrication of single-crystal diamond. The work finds applications in medicine, defence, industry, and communications.

CRISPR/Cas9 technology has been used for genome engineering in vivo. Here, the authors use a transfection technique to deliver multiple guide RNAs to the pancreas of adult mice, allowing genetic screening and chromosome engineering in pancreatic cancer.

Graphene nanoribbons (GNRs) have structure-dependent electronic properties that make them attractive for the fabrication of nanoscale electronic devices, but exploiting this potential has been hindered by the lack of precise production methods. Here the authors demonstrate how to reliably produce different GNRs, using precursor monomers that encode the structure of the targeted nanoribbon and are converted into GNRs by means of surface-assisted coupling.

The release of ancient carbon from thawing permafrost is thought to have an important impact on global biogeochemistry through positive feedbacks. Here Dean and colleagues show that in Siberian permafrost, warming could liberate more contemporary carbon relative to aged counterparts.

The supramammillary nucleus in the hypothalamus acts as a novelty hub that selectively directs different types of novelty signals to different subregions of the hippocampus and flexibly modulates the encoding of memory.

The vibrational states emerging at the interface in oxide superlattices are characterized theoretically and at atomic resolution, showing the impact of material length scales on structure and vibrational response.

Multi-omics profiling of effects of SARS-CoV-2 and SARS-CoV on A549, a lung-derived human cell line, produces a dataset enabling identification of common and virus-specific mechanisms of infection.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive hematologic malignancy derived from the precursors of plasmacytoid dendritic cells. Here the authors characterize the anti-tumor activity of allogeneic anti-CD123 CAR-T cells in preclinical models of BPDCN.

Understanding the factors underlying colonization of donor microbes in recipients of fecal microbiota transplantation is a necessary first step to aid development of directed approaches that aim to couple colonization to clinical outcomes.

The neurotransmitter dopamine is an important regulator of brain function. Here the authors describe “dopamine hub synapses”, where dopamine transmission may act in synergy with other neurotransmitters.