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A simple yet powerful super-resolution imaging approach based on switching off ordinary fluorophores and localizing those remaining or regaining fluorescence is illustrated using continuous widefield illumination and imaging of fixed and living cells labeled with rhodamine-derived dyes or fluorescent proteins. Biteen et al., also in this issue, describe related work using the ordinary fluorophore of EYFP for super-resolution imaging.

Severe COVID-19 requires immediate and targeted intervention that is efficient against SARS-CoV-2 and its variants. Authors show here the therapeutic potential of engineered natural killer cells that simultaneously express a chimeric antigen receptor targeting the spike protein of SARS-CoV-2, and IL-15, a cytokine that enhances the function and survival of their own.

Here, the authors identify interleukin-3 as a predictive marker for severity and outcome of SARS-CoV-2 infection in a multi-center, prospective study and find that patients with severe COVID-19 have reduced circulating plasmacytoid dendritic cell levels compared to non-severe COVID-19 patients.

Multiplexed imaging of synaptic proteins can provide useful information on the heterogeneity of synaptic architecture and plasticity. Here the authors use high affinity locked nucleic acid probes and low affinity DNA imaging probes to achieve multiplexed confocal and super-resolution imaging of synaptic and cytoskeletal proteins.

Analysis of thousands of historical documents recording floods in Europe shows that flooding characteristics in recent decades are unlike those of previous centuries.

How neurons produce energy to fuel fast axonal transport is only partially understood. Authors here report that most glycolytic enzymes are enriched in motile vesicles, and such glycolytic machinery can produce ATP autonomously to propel vesicle movement along microtubules in a cell-free assay.

Event-based sensors enable super-resolution single-molecule localization microscopy with comparable quality and resolution to traditional scientific cameras, while also overcoming the limitations of high-density imaging.

Staufer et al. provide a protocol for preparation of synthetic minimal virions (MiniV) of SARS-CoV-2, mimicking viral structure and allowing for precise investigation of receptor binding mechanism. They find that the highly conserved free fatty acid binding pocket (FABP) can function as an allosteric regulator, enabling adaptation of immunogenicity via binding of proinflammatory free fatty acids and mediating the spike open to-closed equilibrium.

In contrast to direct-targeting monoclonal antibodies, low affinity confers agonistic monoclonal antibodies with more potency.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Here the authors show that extremes in the summer jet stream position over Europe create a beech forest productivity dipole between northwestern and southeastern Europe and can result in regional anomalies in forest carbon uptake and growth.

Frequency-modulated continuous wave LiDAR has suffered from limited 3D frame rates. Here, the authors combine a grating for beam steering with a compressed time-frequency analysis for depth retrieval, and demonstrate real-time densely sampled 3D imaging of moving objects with submillimetre localization accuracy.

In contrast to future projections, paleoclimate records often find wetter subtropics in tandem with elevated CO₂. Here, a compilation of proxies and simulations are used to reveal the climate dynamics and feedbacks responsible for generating wet subtropics during the mid-Pliocene.

Pulmonary large cell neuroendocrine carcinoma is an aggressive subtype of lung cancer. Here, the authors identify distinct subtypes based on genomic alterations and transcriptomic alterations.

Potential mangrove restoration would necessitate an investment of $40.0–52.1 billion, yielding net gains in ESV of $231–725 billion. An estimated of 19.4 Tg C can be sequestrated in mangrove soils, generating $68.6–$236 million via blue C trading.

High-resolution climate models simulate a more realistic relationship between North Atlantic sea surface temperatures and European summer temperature extremes, because of the reduced surface temperature bias in the subpolar North Atlantic.

MicroRNAs regulate haematopoietic stem cell (HSC) development to ensure the correct generation of blood cells. Haetscher et al. show in mice that miR-193b controls the life-long self-renewal ability of HSCs via AKT and STAT5 pathways, with loss of miR-193b accelerating HSC expansion and reducing differentiation.

Macrophages are critical in limiting replication of herpes simplex virus type 1 (HSV-1). Here the authors show how acid ceramidase and its enzymatic product sphingosine enable multivesicular bodies to function as an anti-viral mechanism.

Widespread loss of coastal marshes will occur in the Mediterranean by 2100, ranging from 8% to 92% of current extent, and even total loss in specific regions depending on climate mitigation policies, according to a comprehensive modelling approach that includes sea-level rise, sediment accretion and potential for marsh migration.

Neurons form glutamatergic synapses with glioma cells in mice and humans, and inhibition of AMPA receptors reduces glioma cell invasion and growth.

Forests help to sustain cities and all who live in them. This Review considers barriers to sustaining resilient forests and suggests paths for overcoming them.

A comparison of salt marsh and mangrove channel networks around the world exhibited different network extents. This could be linked to differences in vegetation colonization strategies, with major implications on coastal development.

Nanobodies (Nbs) coupled to organic dyes are increasingly used for super-resolution cell imaging, but producing gene-specific Nbs is time-consuming. Here the authors present a peptide-tag/Nb combination for dSTORM imaging which can be easily adapted to different targets in fixed and live cells.

The Somatic Mosaicism across Human Tissues Network aims to create a reference catalogue of somatic mosaicism across different tissues and cells within individuals.

Mitochondrial cristae organization and ER-mitochondria contact sites are critical structures for cellular function. Here, the authors use super-resolution microscopy to show that Miro GTPases form clusters required for normal ER-mitochondria contact sites formation and to link cristae organization to the mitochondrial transport machinery.

The combination of DNA-PAINT and spinning-disk confocal microscopy makes super-resolution microscopy in whole cells affordable and easy to implement.

Mucosal Associated Invariant T cells have been implicated in response to bacterial pathogens. Here the authors show that in human viral infections, these cells are activated by IL-18 in cooperation with other pro-inflammatory cytokines, producing interferon gamma and granzyme B.

In this Review, the authors describe our current knowledge of the consequences of SARS-CoV-2 infection on the urogenital system, discussing urological symptoms and damage to organs of the genitourinary tract induced by COVID-19 infection. Moreover, the effects of COVID-19 on male fertility and sexual health are discussed.

Patients with cystic fibrosis are not reporting particularly sever outcomes upon SARS-CoV-2 infection. Here, the authors demonstrate decreased ACE2 levels is cystic fibrosis airway epithelia associated with impaired viral entry and replication.

This study uses chromatin tracing to identify alterations in single-cell 3D genome conformation during the progression of Kras-driven mouse lung adenocarcinoma and pancreatic ductal adenocarcinoma, and proposes Rnf2 as a regulator of the 3D genome.

Climate change entails an intensification of extreme weather events that can potentially trigger socioeconomic and energy system disruptions. As we approach 1 °C of global warming we should start learning from historical extremes and explicitly incorporate such events in integrated climate–economy and energy systems models.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

DNA-PAINT is a super-resolution imaging technique which suffers from high background signals and non-specific binding. Here the authors report Repeat DNA-PAINT which is capable of supressing background noise and preventing photoinduced site loss, as well as decreasing the time taken for the sampling process.

Large-scale Mendelian randomization and colocalization analyses using gene expression and soluble protein data for 1,263 actionable druggable genes, which encode protein targets for approved drugs or drugs in clinical development, identify IFNAR2 and ACE2 as the most promising therapeutic targets for early management of COVID-19.

Increased melting is often assumed to cause acceleration of ice sheets and glaciers through basal lubrication, possibly leading to increased rates of sea level rise. Now a physically-based model challenges this view, illustrating that above a critical threshold, increased melt will suppress the dynamic thinning process. Short-term spikes in water delivery, as from lake drainage or precipitation, still have the potential to generate spikes in velocity, but overall increases in melt do not appear likely to cause velocity increases.

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.

Ubiquitination of the receptor FAM134B regulates ER-phagy and remodelling of the endoplasmic reticulum in response to cellular demands.

The relationship between terrestrial carbon sinks and atmospheric modes of variability remains uncertain. Here, the authors show that the coupling of the North Atlantic Oscillation and East-Atlantic patterns explains variations in the European CO₂sink from 1982 to 2012.

Children are less likely to be infected with SARS-CoV-2 and develop less severe disease than adults, which makes estimation of infection rates challenging. Here, the authors conduct seroprevalence surveys of children in Germany, describe changes in prevalence over time, and identify risk factors for infection.

Skyrmions are a special type of particle that has long been predicted to exist in many fields of physics. Direct images of these structures have now been made in a magnetic material.