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Deployed optical clocks will improve positioning for navigational autonomy1, provide remote time standards for geophysical monitoring2and distributed coherent sensing3, allow time synchronization of remote quantum networks4,5and provide operational redundancy for national time standards. Although laboratory optical clocks now reach fractional inaccuracies below 10−18(refs. 6,7), transportable versions of these high-performing clocks8,9have limited utility because of their size, environmental sensitivity and cost10. Here we report the development of optical clocks with the requisite combination of size, performance and environmental insensitivity for operation on mobile platforms. The 35 l clock combines a molecular iodine spectrometer, fibre frequency comb and control electronics. Three of these clocks operated continuously aboard a naval ship in the Pacific Ocean for 20 days while accruing timing errors below 300 ps per day. The clocks have comparable performance to active hydrogen masers in one-tenth the volume. Operating high-performance clocks at sea has been historically challenging and continues to be critical for navigation. This demonstration marks a significant technological advancement that heralds the arrival of future optical timekeeping networks.

Severe influenza A virus (IAV) infections can result in hyper-inflammation, lung injury and acute respiratory distress syndrome1–5(ARDS), for which there are no effective pharmacological therapies. Necroptosis is an attractive entry point for therapeutic intervention in ARDS and related inflammatory conditions because it drives pathogenic lung inflammation and lethality during severe IAV infection6–8and can potentially be targeted by receptor interacting protein kinase 3 (RIPK3) inhibitors. Here we show that a newly developed RIPK3 inhibitor, UH15-38, potently and selectively blocked IAV-triggered necroptosis in alveolar epithelial cells in vivo. UH15-38 ameliorated lung inflammation and prevented mortality following infection with laboratory-adapted and pandemic strains of IAV, without compromising antiviral adaptive immune responses or impeding viral clearance. UH15-38 displayed robust therapeutic efficacy even when administered late in the course of infection, suggesting that RIPK3 blockade may provide clinical benefit in patients with IAV-driven ARDS and other hyper-inflammatory pathologies.

The standard quantum limit bounds the precision of measurements that can be achieved by ensembles of uncorrelated particles. Fundamentally, this limit arises from the non-commuting nature of quantum mechanics, leading to the presence of fluctuations often referred to as quantum projection noise. Quantum metrology relies on the use of non-classical states of many-body systems to enhance the precision of measurements beyond the standard quantum limit1,2. To do so, one can reshape the quantum projection noise—a strategy known as squeezing3,4. In the context of many-body spin systems, one typically uses all-to-all interactions (for example, the one-axis twisting model4) between the constituents to generate the structured entanglement characteristic of spin squeezing5. Here we explore the prediction, motivated by recent theoretical work6–10, that short-range interactions—and in particular, the two-dimensional dipolar XY model—can also enable the realization of scalable spin squeezing. Working with a dipolar Rydberg quantum simulator of up to N= 100 atoms, we demonstrate that quench dynamics from a polarized initial state lead to spin squeezing that improves with increasing system size up to a maximum of −3.5 ± 0.3 dB (before correcting for detection errors, or roughly −5 ± 0.3 dB after correction). Finally, we present two independent refinements: first, using a multistep spin-squeezing protocol allows us to further enhance the squeezing by roughly 1 dB, and second, leveraging Floquet engineering to realize Heisenberg interactions, we demonstrate the ability to extend the lifetime of the squeezed state by freezing its dynamics.

Iron is important in regulating the ocean carbon cycle1. Although several dissolved and particulate species participate in oceanic iron cycling, current understanding emphasizes the importance of complexation by organic ligands in stabilizing oceanic dissolved iron concentrations2–6. However, it is difficult to reconcile this view of ligands as a primary control on dissolved iron cycling with the observed size partitioning of dissolved iron species, inefficient dissolved iron regeneration at depth or the potential importance of authigenic iron phases in particulate iron observational datasets7–12. Here we present a new dissolved iron, ligand and particulate iron seasonal dataset from the Bermuda Atlantic Time-series Study (BATS) region. We find that upper-ocean dissolved iron dynamics were decoupled from those of ligands, which necessitates a process by which dissolved iron escapes ligand stabilization to generate a reservoir of authigenic iron particles that settle to depth. When this ‘colloidal shunt’ mechanism was implemented in a global-scale biogeochemical model, it reproduced both seasonal iron-cycle dynamics observations and independent global datasets when previous models failed13–15. Overall, we argue that the turnover of authigenic particulate iron phases must be considered alongside biological activity and ligands in controlling ocean-dissolved iron distributions and the coupling between dissolved and particulate iron pools.

Pricing credits according to how much carbon is removed, for how long and how reliably, would direct funding to the most effective climate solutions.

White adipose tissue, once regarded as morphologically and functionally bland, is now recognized to be dynamic, plastic and heterogenous, and is involved in a wide array of biological processes including energy homeostasis, glucose and lipid handling, blood pressure control and host defence1. High-fat feeding and other metabolic stressors cause marked changes in adipose morphology, physiology and cellular composition1, and alterations in adiposity are associated with insulin resistance, dyslipidemia and type 2 diabetes2. Here we provide detailed cellular atlases of human and mouse subcutaneous and visceral white fat at single-cell resolution across a range of body weight. We identify subpopulations of adipocytes, adipose stem and progenitor cells, vascular and immune cells and demonstrate commonalities and differences across species and dietary conditions. We link specific cell types to increased risk of metabolic disease and provide an initial blueprint for a comprehensive set of interactions between individual cell types in the adipose niche in leanness and obesity. These data comprise an extensive resource for the exploration of genes, traits and cell types in the function of white adipose tissue across species, depots and nutritional conditions.

The ocean is warming, losing oxygen and being acidified, primarily as a result of anthropogenic carbon emissions. With ocean warming, acidification and deoxygenation projected to increase for decades, extreme events, such as marine heatwaves, will intensify, occur more often, persist for longer periods of time and extend over larger regions. Nevertheless, our understanding of oceanic extreme events that are associated with warming, low oxygen concentrations or high acidity, as well as their impacts on marine ecosystems, remains limited. Compound events—that is, multiple extreme events that occur simultaneously or in close sequence—are of particular concern, as their individual effects may interact synergistically. Here we assess patterns and trends in open ocean extremes based on the existing literature as well as global and regional model simulations. Furthermore, we discuss the potential impacts of individual and compound extremes on marine organisms and ecosystems. We propose a pathway to improve the understanding of extreme events and the capacity of marine life to respond to them. The conditions exhibited by present extreme events may be a harbinger of what may become normal in the future. As a consequence, pursuing this research effort may also help us to better understand the responses of marine organisms and ecosystems to future climate change.

The emergency use authorization of two mRNA vaccines in less than a year from the emergence of SARS-CoV-2 represents a landmark in vaccinology1,2. Yet, how mRNA vaccines stimulate the immune system to elicit protective immune responses is unknown. Here we used a systems vaccinology approach to comprehensively profile the innate and adaptive immune responses of 56 healthy volunteers who were vaccinated with the Pfizer–BioNTech mRNA vaccine (BNT162b2). Vaccination resulted in the robust production of neutralizing antibodies against the wild-type SARS-CoV-2 (derived from 2019-nCOV/USA_WA1/2020) and, to a lesser extent, the B.1.351 strain, as well as significant increases in antigen-specific polyfunctional CD4 and CD8 T cells after the second dose. Booster vaccination stimulated a notably enhanced innate immune response as compared to primary vaccination, evidenced by (1) a greater frequency of CD14+CD16+inflammatory monocytes; (2) a higher concentration of plasma IFNγ; and (3) a transcriptional signature of innate antiviral immunity. Consistent with these observations, our single-cell transcriptomics analysis demonstrated an approximately 100-fold increase in the frequency of a myeloid cell cluster enriched in interferon-response transcription factors and reduced in AP-1 transcription factors, after secondary immunization. Finally, we identified distinct innate pathways associated with CD8 T cell and neutralizing antibody responses, and show that a monocyte-related signature correlates with the neutralizing antibody response against the B.1.351 variant. Collectively, these data provide insights into the immune responses induced by mRNA vaccination and demonstrate its capacity to prime the innate immune system to mount a more potent response after booster immunization.

The development of a portfolio of COVID-19 vaccines to vaccinate the global population remains an urgent public health imperative1. Here we demonstrate the capacity of a subunit vaccine, comprising the SARS-CoV-2 spike protein receptor-binding domain displayed on an I53-50 protein nanoparticle scaffold (hereafter designated RBD–NP), to stimulate robust and durable neutralizing-antibody responses and protection against SARS-CoV-2 in rhesus macaques. We evaluated five adjuvants including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an α-tocopherol-containing oil-in-water emulsion; AS37, a Toll-like receptor 7 (TLR7) agonist adsorbed to alum; CpG1018-alum, a TLR9 agonist formulated in alum; and alum. RBD–NP immunization with AS03, CpG1018-alum, AS37 or alum induced substantial neutralizing-antibody and CD4 T cell responses, and conferred protection against SARS-CoV-2 infection in the pharynges, nares and bronchoalveolar lavage. The neutralizing-antibody response to live virus was maintained up to 180 days after vaccination with RBD–NP in AS03 (RBD–NP-AS03), and correlated with protection from infection. RBD–NP immunization cross-neutralized the B.1.1.7 SARS-CoV-2 variant efficiently but showed a reduced response against the B.1.351 variant. RBD–NP-AS03 produced a 4.5-fold reduction in neutralization of B.1.351 whereas the group immunized with RBD–NP-AS37 produced a 16-fold reduction in neutralization of B.1.351, suggesting differences in the breadth of the neutralizing-antibody response induced by these adjuvants. Furthermore, RBD–NP-AS03 was as immunogenic as a prefusion-stabilized spike immunogen (HexaPro) with AS03 adjuvant. These data highlight the efficacy of the adjuvanted RBD–NP vaccine in promoting protective immunity against SARS-CoV-2 and have led to phase I/II clinical trials of this vaccine (NCT04742738 and NCT04750343).

The SARS-CoV-2 lineage B.1.1.7, designated variant of concern (VOC) 202012/01 by Public Health England1, was first identified in the UK in late summer to early autumn 20202. Whole-genome SARS-CoV-2 sequence data collected from community-based diagnostic testing for COVID-19 show an extremely rapid expansion of the B.1.1.7 lineage during autumn 2020, suggesting that it has a selective advantage. Here we show that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by Sgene target failures (SGTF) in community-based diagnostic PCR testing. Analysis of trends in SGTF and non-SGTF case numbers in local areas across England shows that B.1.1.7 has higher transmissibility than non-VOC lineages, even if it has a different latent period or generation time. The SGTF data indicate a transient shift in the age composition of reported cases, with cases of B.1.1.7 including a larger share of under 20-year-olds than non-VOC cases. We estimated time-varying reproduction numbers for B.1.1.7 and co-circulating lineages using SGTF and genomic data. The best-supported models did not indicate a substantial difference in VOC transmissibility among different age groups, but all analyses agreed that B.1.1.7 has a substantial transmission advantage over other lineages, with a 50% to 100% higher reproduction number.

Spinal cord injury (SCI) induces haemodynamic instability that threatens survival1–3, impairs neurological recovery4,5, increases the risk of cardiovascular disease6,7, and reduces quality of life8,9. Haemodynamic instability in this context is due to the interruption of supraspinal efferent commands to sympathetic circuits located in the spinal cord10, which prevents the natural baroreflex from controlling these circuits to adjust peripheral vascular resistance. Epidural electrical stimulation (EES) of the spinal cord has been shown to compensate for interrupted supraspinal commands to motor circuits below the injury11, and restored walking after paralysis12. Here, we leveraged these concepts to develop EES protocols that restored haemodynamic stability after SCI. We established a preclinical model that enabled us to dissect the topology and dynamics of the sympathetic circuits, and to understand how EES can engage these circuits. We incorporated these spatial and temporal features into stimulation protocols to conceive a clinical-grade biomimetic haemodynamic regulator that operates in a closed loop. This ‘neuroprosthetic baroreflex’ controlled haemodynamics for extended periods of time in rodents, non-human primates and humans, after both acute and chronic SCI. We will now conduct clinical trials to turn the neuroprosthetic baroreflex into a commonly available therapy for people with SCI.

Up to 20% of people worldwide develop gastrointestinal symptoms following a meal1, leading to decreased quality of life, substantial morbidity and high medical costs. Although the interest of both the scientific and lay communities in this issue has increased markedly in recent years, with the worldwide introduction of gluten-free and other diets, the underlying mechanisms of food-induced abdominal complaints remain largely unknown. Here we show that a bacterial infection and bacterial toxins can trigger an immune response that leads to the production of dietary-antigen-specific IgE antibodies in mice, which are limited to the intestine. Following subsequent oral ingestion of the respective dietary antigen, an IgE- and mast-cell-dependent mechanism induced increased visceral pain. This aberrant pain signalling resulted from histamine receptor H1-mediated sensitization of visceral afferents. Moreover, injection of food antigens (gluten, wheat, soy and milk) into the rectosigmoid mucosa of patients with irritable bowel syndrome induced local oedema and mast cell activation. Our results identify and characterize a peripheral mechanism that underlies food-induced abdominal pain, thereby creating new possibilities for the treatment of irritable bowel syndrome and related abdominal pain disorders.

Severe respiratory infections can result in acute respiratory distress syndrome (ARDS)1. There are no effective pharmacological therapies that have been shown to improve outcomes for patients with ARDS. Although the host inflammatory response limits spread of and eventually clears the pathogen, immunopathology is a major contributor to tissue damage and ARDS1,2. Here we demonstrate that respiratory viral infection induces distinct fibroblast activation states, which we term extracellular matrix (ECM)-synthesizing, damage-responsive and interferon-responsive states. We provide evidence that excess activity of damage-responsive lung fibroblasts drives lethal immunopathology during severe influenza virus infection. By producing ECM-remodelling enzymes—in particular the ECM protease ADAMTS4—and inflammatory cytokines, damage-responsive fibroblasts modify the lung microenvironment to promote robust immune cell infiltration at the expense of lung function. In three cohorts of human participants, the levels of ADAMTS4 in the lower respiratory tract were associated with the severity of infection with seasonal or avian influenza virus. A therapeutic agent that targets the ECM protease activity of damage-responsive lung fibroblasts could provide a promising approach to preserving lung function and improving clinical outcomes following severe respiratory infections.

Coronaviruses are prone to transmission to new host species, as recently demonstrated by the spread to humans of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) pandemic1. Small animal models that recapitulate SARS-CoV-2 disease are needed urgently for rapid evaluation of medical countermeasures2,3. SARS-CoV-2 cannot infect wild-type laboratory mice owing to inefficient interactions between the viral spike protein and the mouse orthologue of the human receptor, angiotensin-converting enzyme 2 (ACE2)4. Here we used reverse genetics5to remodel the interaction between SARS-CoV-2 spike protein and mouse ACE2 and designed mouse-adapted SARS-CoV-2 (SARS-CoV-2 MA), a recombinant virus that can use mouse ACE2 for entry into cells. SARS-CoV-2 MA was able to replicate in the upper and lower airways of both young adult and aged BALB/c mice. SARS-CoV-2 MA caused more severe disease in aged mice, and exhibited more clinically relevant phenotypes than those seen in Hfh4-ACE2transgenic mice, which express human ACE2 under the control of the Hfh4(also known as Foxj1) promoter. We demonstrate the utility of this model using vaccine-challenge studies in immune-competent mice with native expression of mouse ACE2. Finally, we show that the clinical candidate interferon-?1a (IFN-?1a) potently inhibits SARS-CoV-2 replication in primary human airway epithelial cells in vitro—both prophylactic and therapeutic administration of IFN-?1a diminished SARS-CoV-2 replication in mice. In summary, the mouse-adapted SARS-CoV-2 MA model demonstrates age-related disease pathogenesis and supports the clinical use of pegylated IFN-?1a as a treatment for human COVID-196.

The ocean’s ability to sequester carbon away from the atmosphere exerts an important control on global climate. The biological pump drives carbon storage in the deep ocean and is thought to function via gravitational settling of organic particles from surface waters. However, the settling flux alone is often insufficient to balance mesopelagic carbon budgets or to meet the demands of subsurface biota. Here we review additional biological and physical mechanisms that inject suspended and sinking particles to depth. We propose that these ‘particle injection pumps’ probably sequester as much carbon as the gravitational pump, helping to close the carbon budget and motivating further investigation into their environmental control.

Tweaks to treaty that targeted the ozone hole could help to fight powerful greenhouse gasses.

As global temperatures rise, large amounts of carbon sequestered in permafrost are becoming available for microbial degradation. Accurate prediction of carbon gas emissions from thawing permafrost is limited by our understanding of these microbial communities. Here we use metagenomic sequencing of 214 samples from a permafrost thaw gradient to recover 1,529 metagenome-assembled genomes, including many from phyla with poor genomic representation. These genomes reflect the diversity of this complex ecosystem, with genus-level representatives for more than sixty per cent of the community. Meta-omic analysis revealed key populations involved in the degradation of organic matter, including bacteria whose genomes encode a previously undescribed fungal pathway for xylose degradation. Microbial and geochemical data highlight lineages that correlate with the production of greenhouse gases and indicate novel syntrophic relationships. Our findings link changing biogeochemistry to specific microbial lineages involved in carbon processing, and provide key information for predicting the effects of climate change on permafrost systems. Analysis of more than 1,500 microbial genomes sheds light on the processing of carbon released as permafrost thaws.

Reward the creation of analyses for policymakers that are inclusive, rigorous, transparent and accessible, urge Christl A. Donnelly and colleagues. Reward the creation of analyses for policymakers that are inclusive, rigorous, transparent and accessible.

T cell receptor (TCR) sequences are very diverse, with many more possible sequence combinations than T cells in any one individual. Here we define the minimal requirements for TCR antigen specificity, through an analysis of TCR sequences using a panel of peptide and major histocompatibility complex (pMHC)-tetramer-sorted cells and structural data. From this analysis we developed an algorithm that we term GLIPH (grouping of lymphocyte interactions by paratope hotspots) to cluster TCRs with a high probability of sharing specificity owing to both conserved motifs and global similarity of complementarity-determining region 3 (CDR3) sequences. We show that GLIPH can reliably group TCRs of common specificity from different donors, and that conserved CDR3 motifs help to define the TCR clusters that are often contact points with the antigenic peptides. As an independent validation, we analysed 5,711 TCRβ chain sequences from reactive CD4 T cells from 22 individuals with latent Mycobacterium tuberculosis infection. We found 141 TCR specificity groups, including 16 distinct groups containing TCRs from multiple individuals. These TCR groups typically shared HLA alleles, allowing prediction of the likely HLA restriction, and a large number of M. tuberculosis T cell epitopes enabled us to identify pMHC ligands for all five of the groups tested. Mutagenesis and de novo TCR design confirmed that the GLIPH-identified motifs were critical and sufficient for shared-antigen recognition. Thus the GLIPH algorithm can analyse large numbers of TCR sequences and define TCR specificity groups shared by TCRs and individuals, which should greatly accelerate the analysis of T cell responses and expedite the identification of specific ligands.

The micronutrient iron is now recognized to be important in regulating the magnitude and dynamics of ocean primary productivity, making it an integral component of the ocean’s biogeochemical cycles. In this Review, we discuss how a recent increase in observational data for this trace metal has challenged the prevailing view of the ocean iron cycle. Instead of focusing on dust as the major iron source and emphasizing iron’s tight biogeochemical coupling to major nutrients, a more complex and diverse picture of the sources of iron, its cycling processes and intricate linkages with the ocean carbon and nitrogen cycles has emerged.

The authors test several candidate vaccines for Zika virus in mouse models and show that single-shot DNA vaccines and inactivated virus vaccines provide complete protection against Zika virus isolates from Brazil and Puerto Rico.

Nitrogen is the most abundant trace element in natural1and meteoritic2diamond and finds its way into synthetic diamonds during their manufacture3. In the first study of the isotopic composition in a synthetic diamond, we have found that nitrogen incorporated in a large (∼0.5 cm diameter) cubo-octahedron is isotopically fractionated between the zones of different crystal habit. The cubic {100} sector of the stone, which contains about half the concentration of nitrogen, is enriched by ∼4.5% in the heavy (15N) isotope of the element relative to the octahedral {111} growth region. This is the largest isotopic fractionation yet observed that can be attributed to the influence of crystal structure and demonstrates again the idiosyncratic behaviour of diamond with respect to nitrogen.

The application of laser radiation to the processing of silicon and silicon-based solid state devices has developed in the past two decades. A few of these techniques are becoming established practice in the semiconductor industry, whilst others remain the subject of research and heated debate. Techniques include the solid phase and the liquid phase regrowth of amorphous silicon layers, together with the more novel application of laser photochemistry.

Many biological processes depend on the function of proteins that detect changes in a cell's environment and transmit the information to the cytoplasm, for example, peptide hormone receptors1. In Escherichia coli this class of proteins is exemplified by the sensory transducers (also called signalling proteins or methyl-accepting chemotaxis proteins) which have a central role in mediating chemotactic behaviour2,3. The sensory transducers are the products of four genes: tsr, tar, tap and trg. Each transducer detects changes in the environmental concentration of one or a very few attractants: Tsr, serine; Tar, aspartate and maltose; Tap, unknown; and Trg, ribose and galactose. Tsr and Tar act directly as chemoreceptors for the amino acid attractants4,5and signal changes in their degree of occupancy to the flagellar apparatus. Detection of these changes in occupancy is made possible as the transducers are methylated at multiple glutamate residues6–9such that their level of methylation reflects the most recent chemoeffector concentration. Biochemical10,11and genetic12,13information concerning the serine transducer protein has been accumulating rapidly but little is known about the structure of the molecule. We present here the nucleotide sequence of the tsr gene of E. coli; the amino acid sequence derived from it suggests that the Tsr transducer protein has a relatively simple transmembrane structure that may place limits on the mechanisms available for the transmission of sensory information into the cell.

High-resolution seismic reflection data indicate the presence of huge sub-surface channel networks on the outer Nova Scotian continental shelf. Channel axes extend to over 450 m below present sea level (b.s.l.). Channel walls average 2–3 km in width. Mechanisms capable of producing such channels include fluvial, submarine canyon or glacial erosion. Considerable debate has focused on the positions of the Tertiary/Quaternary (T/Q) and Pleistocene/ Holocene (P/H) boundaries1–4in this region and the relationship of the T/Q boundary to the unconformity at the base of the channel networks. Uncertainty also surrounds the extent of Pleistocene ice sheets on the south-east Canadian continental margin4–7. Here we present a new stratigraphy for the Sable Island region (Fig. 1) based on seismic profiles, with lithologic and biostratigraphic control provided by two strategically placed boreholes. This strati-graphic analysis establishes the positions of the T/Q and P/H boundaries outside the valleys at 51 m and 220 m b.s.l. respectively. Our analysis also implies that the large channel systems are tunnel valleys, cut by a sub-ice meltwater process under a pre- to early Wisconsinan ice sheet which extended close to the shelf edge.

Kimberlites are characterized by a high concentration of incompatible elements, including light rare earths. However, Nd isotopic evidence indicates that their source regions do not have a long history of enrichment. If kimberlites can be generated from non-enriched mantle sources by simple partial melting processes, this implies that crystal–liquid partition coefficients for some trace elements are lower for kimberlitic liquids than for basalts or andesites. From a comparison of clinopyroxene megacrysts (regarded as equilibrated with kimberlite at depth) with existing kimberlite data we argue here that low crystal–liquid partition coefficients for the rare earths are plausible.

We propose that, the binding site for the complement subcomponent C1q on immunoglobulin G involves the last two (C-terminal) β-strands of the Cγ2 domain. This region contains a large number of accessible and highly conserved charged residues and charge is postulated as an important component of the C1q–IgG interaction. The conclusions are reached on the basis of accessibility and sequence conservation analyses of Cγ2 amino acid residues, the use of specific inhibitors and chemical modification studies.

Decontamination of hazardous wastes containing dioxins (dibenzo-p-dioxin and its chlorinated analogues) remains a serious problem and new approaches for the degradation or alteration of dioxins are needed. We describe here dibenzo-p-dioxin radical cation formation and polymerization on a simple clay mineral (Cu(II)-smectite) in mild reaction conditions. Existence of the radical species was conclusively demonstrated using electron spin resonance (ESR), ultraviolet-visible, and infrared spectroscopy. The radical cation polymerized to form dimers and trimers as revealed by mass spectroscopy. Radical cations of 1- and 2-chlorodibenzo-p-dioxin were also formed on Cu(II)-smectite. The radical cations are formed by electron transfer from the dioxins to Cu(II). The formation of dioxin radicals may provide the basis for new detoxification methods in which the reactive radical species is coupled to other molecules or degraded by subsequent reactions.

Information can now be read in the form of an extended spatial distribution of charge. The technique involved shows considerable promise for use in spectrometry.

A Correction to this paper has been published: https://doi.org/10.1038/s41586-020-03107-5

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Variation in the degree of methylation of DNA seems to be one mode of regulating gene expression in eukaryotic cells1–7. The relationship between DNA demethylation and gene activation observed in globin4–6and viral2genes, together with evidence that alterations in the degree of DNA methylation of a gene are heritable8, although not with 100% fidelity9, have suggested that this may be a mechanism of control of differentiation. Futhermore, exposure to the demethylating drug 5-azacytidine (5-AC) causes differentiation of 3T3 cells into striated muscle cells, chondrocytes and adipocytes7. Subsequent studies have shown that these effects are due to DNA demethylation10. In view of these observations, we have now attempted to modify several continuous B-cell lines with 5-AC. Following exposure of the pre-B lymphoma ABLS 8.1 to 5-AC, we have derived cloned cell lines which possess macrophage-like characteristics not expressed by ABLS 8.1. Similar macrophage-like cell lines were obtained in two independent experiments; they have been re-cloned and remain stable after 4 months of continuous culture.

THE uptake of amino acids and of some monosaccharides into the intestinal mucosal cell across the brush-border membranes requires sodium in the intestinal lumen1–3. An hypothesis of the existence in brush-border membranes of systems for transport that depend on Na—for example, the ‘Na gradient’ hypothesis4—although necessary, is not sufficient to account for all the effects of Na on epithelial transport. Whereas in in vitro conditions5the accumulation of amino acids and monosaccharides within the epithelium depends markedly on Na in the intestinal lumen, movement of these substances from the lumen into the blood in in vivo conditions is less dependent on Na in the lumen6–9.