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Understanding the nanoscopic chemical and structural changes that drive instabilities in emerging energy materials is essential for mitigating device degradation. The power conversion efficiency of halide perovskite photovoltaic devices has reached 25.7 per cent in single-junction and 29.8 per cent in tandem perovskite/silicon cells1,2, yet retaining such performance under continuous operation has remained elusive3. Here we develop a multimodal microscopy toolkit to reveal that in leading formamidinium-rich perovskite absorbers, nanoscale phase impurities, including hexagonal polytype and lead iodide inclusions, are not only traps for photoexcited carriers, which themselves reduce performance4,5, but also, through the same trapping process, are sites at which photochemical degradation of the absorber layer is seeded. We visualize illumination-induced structural changes at phase impurities associated with trap clusters, revealing that even trace amounts of these phases, otherwise undetected with bulk measurements, compromise device longevity. The type and distribution of these unwanted phase inclusions depends on the film composition and processing, with the presence of polytypes being most detrimental for film photo-stability. Importantly, we reveal that both performance losses and intrinsic degradation processes can be mitigated by modulating these defective phase impurities, and demonstrate that this requires careful tuning of local structural and chemical properties. This multimodal workflow to correlate the nanoscopic landscape of beam-sensitive energy materials will be applicable to a wide range of semiconductors for which a local picture of performance and operational stability has yet to be established.

The Omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was initially identified in November 2021 in South Africa and Botswana, as well as in a sample from a traveller from South Africa in Hong Kong1,2. Since then, Omicron has been detected globally. This variant appears to be at least as infectious as Delta (B.1.617.2), has already caused superspreader events3, and has outcompeted Delta within weeks in several countries and metropolitan areas. Omicron hosts an unprecedented number of mutations in its spike gene and early reports have provided evidence for extensive immune escape and reduced vaccine effectiveness2,4–6. Here we investigated the virus-neutralizing and spike protein-binding activity of sera from convalescent, double mRNA-vaccinated, mRNA-boosted, convalescent double-vaccinated and convalescent boosted individuals against wild-type, Beta (B.1.351) and Omicron SARS-CoV-2 isolates and spike proteins. Neutralizing activity of sera from convalescent and double-vaccinated participants was undetectable or very low against Omicron compared with the wild-type virus, whereas neutralizing activity of sera from individuals who had been exposed to spike three or four times through infection and vaccination was maintained, although at significantly reduced levels. Binding to the receptor-binding and N-terminal domains of the Omicron spike protein was reduced compared with binding to the wild type in convalescent unvaccinated individuals, but was mostly retained in vaccinated individuals.

Malaria has had a major effect on the human genome, with many protective polymorphisms—such as the sickle-cell trait—having been selected to high frequencies in malaria-endemic regions1,2. The blood group variant Dantu provides 74% protection against all forms of severe malaria in homozygous individuals3–5, a similar degree of protection to that afforded by the sickle-cell trait and considerably greater than that offered by the best malaria vaccine. Until now, however, the protective mechanism has been unknown. Here we demonstrate the effect of Dantu on the ability of the merozoite form of the malaria parasite Plasmodium falciparumto invade red blood cells (RBCs). We find that Dantu is associated with extensive changes to the repertoire of proteins found on the RBC surface, but, unexpectedly, inhibition of invasion does not correlate with specific RBC–parasite receptor–ligand interactions. By following invasion using video microscopy, we find a strong link between RBC tension and merozoite invasion, and identify a tension threshold above which invasion rarely occurs, even in non-Dantu RBCs. Dantu RBCs have higher average tension than non-Dantu RBCs, meaning that a greater proportion resist invasion. These findings provide both an explanation for the protective effect of Dantu, and fresh insight into why the efficiency of P. falciparuminvasion might vary across the heterogenous populations of RBCs found both within and between individuals.

Halide perovskite materials have promising performance characteristics for low-cost optoelectronic applications. Photovoltaic devices fabricated from perovskite absorbers have reached power conversion efficiencies above 25 per cent in single-junction devices and 28 per cent in tandem devices1,2. This strong performance (albeit below the practical limits of about 30 per cent and 35 per cent, respectively3) is surprising in thin films processed from solution at low-temperature, a method that generally produces abundant crystalline defects4. Although point defects often induce only shallow electronic states in the perovskite bandgap that do not affect performance5, perovskite devices still have many states deep within the bandgap that trap charge carriers and cause them to recombine non-radiatively. These deep trap states thus induce local variations in photoluminescence and limit the device performance6. The origin and distribution of these trap states are unknown, but they have been associated with light-induced halide segregation in mixed-halide perovskite compositions7and with local strain8, both of which make devices less stable9. Here we use photoemission electron microscopy to image the trap distribution in state-of-the-art halide perovskite films. Instead of a relatively uniform distribution within regions of poor photoluminescence efficiency, we observe discrete, nanoscale trap clusters. By correlating microscopy measurements with scanning electron analytical techniques, we find that these trap clusters appear at the interfaces between crystallographically and compositionally distinct entities. Finally, by generating time-resolved photoemission sequences of the photo-excited carrier trapping process10,11, we reveal a hole-trapping character with the kinetics limited by diffusion of holes to the local trap clusters. Our approach shows that managing structure and composition on the nanoscale will be essential for optimal performance of halide perovskite devices.

Epigenetic aberrations are widespread in cancer, yet the underlying mechanisms and causality remain poorly understood1–3. A subset of gastrointestinal stromal tumours (GISTs) lack canonical kinase mutations but instead have succinate dehydrogenase (SDH) deficiency and global DNA hyper-methylation4,5. Here, we associate this hyper-methylation with changes in genome topology that activate oncogenic programs. To investigate epigenetic alterations systematically, we mapped DNA methylation, CTCF insulators, enhancers, and chromosome topology in KIT-mutant, PDGFRA-mutant and SDH-deficient GISTs. Although these respective subtypes shared similar enhancer landscapes, we identified hundreds of putative insulators where DNA methylation replaced CTCF binding in SDH-deficient GISTs. We focused on a disrupted insulator that normally partitions a core GIST super-enhancer from the FGF4oncogene. Recurrent loss of this insulator alters locus topology in SDH-deficient GISTs, allowing aberrant physical interaction between enhancer and oncogene. CRISPR-mediated excision of the corresponding CTCF motifs in an SDH-intact GIST model disrupted the boundary between enhancer and oncogene, and strongly upregulated FGF4expression. We also identified a second recurrent insulator loss event near the KIToncogene, which is also highly expressed across SDH-deficient GISTs. Finally, we established a patient-derived xenograft (PDX) from an SDH-deficient GIST that faithfully maintains the epigenetics of the parental tumour, including hypermethylation and insulator defects. This PDX model is highly sensitive to FGF receptor (FGFR) inhibition, and more so to combined FGFR and KIT inhibition, validating the functional significance of the underlying epigenetic lesions. Our study reveals how epigenetic alterations can drive oncogenic programs in the absence of canonical kinase mutations, with implications for mechanistic targeting of aberrant pathways in cancers.

Boreal forest fires emit large amounts of carbon into the atmosphere primarily through the combustion of soil organic matter1–3. During each fire, a portion of this soil beneath the burned layer can escape combustion, leading to a net accumulation of carbon in forests over multiple fire events4. Climate warming and drying has led to more severe and frequent forest fires5–7, which threaten to shift the carbon balance of the boreal ecosystem from net accumulation to net loss1, resulting in a positive climate feedback8. This feedback will occur if organic-soil carbon that escaped burning in previous fires, termed ‘legacy carbon’, combusts. Here we use soil radiocarbon dating to quantitatively assess legacy carbon loss in the 2014 wildfires in the Northwest Territories of Canada2. We found no evidence for the combustion of legacy carbon in forests that were older than the historic fire-return interval of northwestern boreal forests9. In forests that were in dry landscapes and less than 60 years old at the time of the fire, legacy carbon that had escaped burning in the previous fire cycle was combusted. We estimate that 0.34 million hectares of young forests (<60 years) that burned in the 2014 fires could have experienced legacy carbon combustion. This implies a shift to a domain of carbon cycling in which these forests become a net source—instead of a sink—of carbon to the atmosphere over consecutive fires. As boreal wildfires continue to increase in size, frequency and intensity7, the area of young forests that experience legacy carbon combustion will probably increase and have a key role in shifting the boreal carbon balance.

Acetylation of histones by lysine acetyltransferases (KATs) is essential for chromatin organization and function1. Among the genes coding for the MYST family of KATs (KAT5–KAT8) are the oncogenes KAT6A(also known as MOZ) and KAT6B(also known as MORFand QKF)2,3. KAT6Ahas essential roles in normal haematopoietic stem cells4–6and is the target of recurrent chromosomal translocations, causing acute myeloid leukaemia7,8. Similarly, chromosomal translocations in KAT6Bhave been identified in diverse cancers8. KAT6A suppresses cellular senescence through the regulation of suppressors of the CDKN2Alocus9,10, a function that requires its KAT activity10. Loss of one allele of KAT6Aextends the median survival of mice with MYC-induced lymphoma from 105 to 413 days11. These findings suggest that inhibition of KAT6A and KAT6B may provide a therapeutic benefit in cancer. Here we present highly potent, selective inhibitors of KAT6A and KAT6B, denoted WM-8014 and WM-1119. Biochemical and structural studies demonstrate that these compounds are reversible competitors of acetyl coenzyme A and inhibit MYST-catalysed histone acetylation. WM-8014 and WM-1119 induce cell cycle exit and cellular senescence without causing DNA damage. Senescence is INK4A/ARF-dependent and is accompanied by changes in gene expression that are typical of loss of KAT6A function. WM-8014 potentiates oncogene-induced senescence in vitro and in a zebrafish model of hepatocellular carcinoma. WM-1119, which has increased bioavailability, arrests the progression of lymphoma in mice. We anticipate that this class of inhibitors will help to accelerate the development of therapeutics that target gene transcription regulated by histone acetylation. Selective inhibitors of KAT6A and KAT6B inhibit MYST-catalysed histone acetylation, induce cell cycle exit and cellular senescence without causing DNA damage, and arrest lymphoma progression in mouse models.

The tropical forests of Borneo and Amazonia may each contain more tree species diversity in half a square kilometre than do all the temperate forests of Europe, North America, and Asia combined. Biologists have long been fascinated by this disparity, using it to investigate potential drivers of biodiversity. Latitudinal variation in many of these drivers is expected to create geographic differences in ecological and evolutionary processes, and evidence increasingly shows that tropical ecosystems have higher rates of diversification, clade origination, and clade dispersal. However, there is currently no evidence to link gradients in ecological processes within communities at a local scale directly to the geographic gradient in biodiversity. Here, we show geographic variation in the storage effect, an ecological mechanism that reduces the potential for competitive exclusion more strongly in the tropics than it does in temperate and boreal zones, decreasing the ratio of interspecific-to-intraspecific competition by 0.25% for each degree of latitude that an ecosystem is located closer to the Equator. Additionally, we find evidence that latitudinal variation in climate underpins these differences; longer growing seasons in the tropics reduce constraints on the seasonal timing of reproduction, permitting lower recruitment synchrony between species and thereby enhancing niche partitioning through the storage effect. Our results demonstrate that the strength of the storage effect, and therefore its impact on diversity within communities, varies latitudinally in association with climate. This finding highlights the importance of biotic interactions in shaping geographic diversity patterns, and emphasizes the need to understand the mechanisms underpinning ecological processes in greater detail than has previously been appreciated.

It is widely accepted that complex interactions between cancer cells and their surrounding microenvironment contribute to disease development, chemo-resistance and disease relapse. In light of this observed interdependency, novel therapeutic interventions that target specific cancer stroma cell lineages and their interactions are being sought. Here we studied a mouse model of human T-cell acute lymphoblastic leukaemia (T-ALL) and used intravital microscopy to monitor the progression of disease within the bone marrow at both the tissue-wide and single-cell level over time, from bone marrow seeding to development/selection of chemo-resistance. We observed highly dynamic cellular interactions and promiscuous distribution of leukaemia cells that migrated across the bone marrow, without showing any preferential association with bone marrow sub-compartments. Unexpectedly, this behaviour was maintained throughout disease development, from the earliest bone marrow seeding to response and resistance to chemotherapy. Our results reveal that T-ALL cells do not depend on specific bone marrow microenvironments for propagation of disease, nor for the selection of chemo-resistant clones, suggesting that a stochastic mechanism underlies these processes. Yet, although T-ALL infiltration and progression are independent of the stroma, accumulated disease burden leads to rapid, selective remodelling of the endosteal space, resulting in a complete loss of mature osteoblastic cells while perivascular cells are maintained. This outcome leads to a shift in the balance of endogenous bone marrow stroma, towards a composition associated with less efficient haematopoietic stem cell function. This novel, dynamic analysis of T-ALL interactions with the bone marrow microenvironment in vivo, supported by evidence from human T-ALL samples, highlights that future therapeutic interventions should target the migration and promiscuous interactions of cancer cells with the surrounding microenvironment, rather than specific bone marrow stroma, to combat the invasion by and survival of chemo-resistant T-ALL cells.

The interaction of comets with the solar wind depends on the ionization of the heavy cometary neutrals (mostly H2O and its dissociation products O, OH) which flow out from the nucleus, and the coupling of these newly produced cometary ions with the solar wind through its embedded magnetic field. The 'pick-up' of these heavy ions slows the solar wind such that a shock may form. As expected, the structure of such a shock transition is highly complex because the gyroradius of a heavy cometary ion is much larger than that of a solar wind proton. Here we present a comparative study of the solar wind electrons and protons and the cometary pick-up ions measured by Giotto at the inbound crossing of the bow shock at comet Halley. We find a highly structured shock transition starting with a cometary ion 'foot' seen at a distance on the order of the cometary ion gyroradius upstream from a sharp decrease in the solar wind proton speed. The total solar wind thermal and magnetic pressure is dominated by the relatively small population of cometary ions throughout the shock region.

The aurora is caused by showers of atomic particles in the upper atmosphere, but there are uncertainties about the particles' movements just before they strike the atmosphere. The mechanism responsible for the pulsating aurora would help us to understand what happens in those last few seconds.

UKS observations of the ionized barium and disturbed natural plasmas 170 km from the centre of the artificial comet release of 27 December 1984 lasted over 4 minutes. During this disturbance, solar-wind ions were retarded and deflected southwards and dawnwards, while barium was accelerated northwards. Substantial electron energization was seen throughout, varying with time and with the energy of the source electrons. Rapid electron and ion density changes were observed in later stages

The supersonic solar wind possesses a variety of simple small scale (<10-min observation duration) phenomena, including discontinuities1–3and magnetic holes4,5. We report here recent AMPTE-UKS6(Active Magnetospheric Particle Tracer Explorer–UK Satellite) observations, however, which reveal a dramatic new complex structure within the solar wind flow. In the plasma and field observations of this magnetic hole/current sheet system, the layers surrounding the strong rotation in the magnetic field contain compressed and heated solar wind, an enhanced field strength and considerable wave activity. The interior region shows strong ion heating but with ambient densities and a fluctuating magnetic field which dips to low values. The bulk flow velocity inside is deflected sharply from the anti-sunward direction, but not in the direction predicted by magnetic stresses across the boundary. The structure is expanding in thickness and is relatively young. The source of momentum and energy for this event remains unclear, and could even be magnetospheric.

ADP–ribosyl transferase (ADPRT) is a DNA-dependent nuclear enzyme which covalently attaches ADP–ribose moieties derived from NAD to proteins to form mono- or poly-ADP–ribosyl derivatives1,2. ADPRT activity is strongly stimulated by breaks in DNA3,4and the enzyme is required for efficient DNA repair5–7. Several reports have suggested that the metabolism of poly- or mono-(ADP–ribose) might also be involved in differentiation in various eukaryotes1,2,8–12. In the most convincing of these, inhibitors of ADPRT were shown to block the differentiation of chick myoblasts in vitro11,12, and differentiation was accompanied by the appearance of single-strand breaks in DNA. We present here evidence that ADPRT activity is obligatory early in the mitogen-induced activation of human peripheral blood lymphocytes. The requirement for this enzyme coincides with a rapid (1–8 h) rejoining of single-strand breaks present in the DNA of quiescent lymphocytes. Hence, DNA breaking and rejoining, regulated by ADPRT, may be involved in a general mechanism of differentiation.

Should engineers be taught at university in the same way as scientists ? In what follows, the author expands on a talk to the Midlands Branch of the Institution of Chemical Engineers at Loughborough University on February 22.

THE analysis of the frequency response to sound of individual nerve fibres in the orthopteran ear indicates that the fibres are most sensitive at a particular frequency (usually between 4 and 6 kHz), but that this frequency tends to be the same for all fibres1,2. The functional significance of this tuning may be associated with the fact that the maximum energy in the mating call lies in the 4.5–5.5 kHz range3. Little is known about the nature of the mechanism that contributes to the tuning curve itself. We have tried to discover if the tuning curve is simply mechanically determined or whether additional sensory/neural elements are involved.

IT is generally recognised that the Earth's magnetic tail and the plasma sheet play a vital role in the processes responsible for the observational phenomenon known as the magnetospheric substorm. Many different models1–5of substorm behaviour have been described with differing degrees of success, and to propose another requires some justification. A new model, if it is to be useful, must do two things. It must be specific enough to make quantitative theoretical analysis possible, and it must fit the morphological features more completely or in a more elegant way than other models. In addition, it should be distinctive enough from other models to be separated from them by observational tests. I believe the model presented here has those properties.

Size constancy is a term used to refer to the fact that objects seem to maintain size as their distance from an observer changes, despite change in image size. it is known that size constancy has limits1,2. People seen from the top of tall buildings look small. By observing objects, including the Moon, and after-images, we demonstrate here that size constancy holds when image size is above half a degree, and breaks down when it is less. In other words, image size is scaled for distance only when image size is above half a degree.

THE translocation hypothesis1,2states that in the process of antibody synthesis any one of a number of immunoglobulin heavy chain V genes is available for union with any of the class-specific C genes. Whereas almost all structural data support the widely held view that all V genes are able to translocate to any of the class-specific C genes, some data suggest that this may not be the case. Wilkinson3found the N-terminal sequence PCA–Ser–Ser (PCA, pyrrolidone carboxylic acid) to be present in a rabbit α chain preparation but absent in pooled rabbit γ chains. Other workers4,5have described an N-terminal heavy chain sequence apparently confined to the IgM class of human immunoglobulins.

IN connection with the clear exposition of the true dimensions of electrical units given by Prof. Rücker in NATURE of the 22nd ult. it is well to bear in mind that Maxwell long before the publication of his book, namely, in the first report to the British Association on electrical standards (see report of the Newcastle meeting of the Association in 1863, p. 160) called attention, in a “Note on the Table of Dimensions,” to the provisional character of the electrostatic and electromagnetic series recommended by the committee, and since widely adopted.

VESPERTILIONID bats produce FM echolocation pulses which sweep through a broad ultrasonic range1,2. Neurophysiological3,4and behavioural5evidence indicates that Myotis lucifugus, the most intensively studied of the vespertilionids, is maximally sensitive to the frequencies of its cries. The small size and mass of the middle ear structures in Microchiroptera6suggest that the transduction system is specialized for the reception of ultrasound. It is obvious that the bat middle ear must respond to high ultrasonic frequencies, but it is not known how efficient the middle ear is, or whether this is achieved by tuned resonances or by a broad-band response. We have used the Mössbauer technique to investigate the contribution of the tympanic membrane to this high-frequency sensitivity. Although our primary interest was in the high-frequency response, we examined a broad range from 1 to 100 kHz.

ALTHOUGH earlier work had suggested that the species methylene, CH2, could participate in “insertion” reactions into C—H and C—Cl bonds1,2, it has recently been shown that in the gas phase reaction of methylene with methyl chloride the course of reaction is best described by a radical abstraction–recombination mechanism3,4. It was shown that both ethane and dichloroethane appeared at rates at least as great as the rate at which ethyl chloride (the true “insertion” product) was formed in the reaction. The electronic state of the methylene may, however, determine the reaction path, and there is some evidence that it is excited singlet methylene which undergoes the insertion reaction5,6. Methylene is most conveniently prepared by the photolysis of ketene7or diazomethane8, and the proportion of triplet (ground state) and singlet methylene formed depends on the precursor and the wave-length of the radiation used for photolysis9,10, more singlet being formed at shorter wavelengths. We wished to investigate the effect of change of excess energy in methylene on the course of reaction, and we present here preliminary results.

IT is well established that high-purity chromium can be produced by electrolysing an aqueous solution of chromic acid containing a small sulphate addition, and that a significant factor governing the purity of such material is the temperature of the electrolyte1. Oxygen and nitrogen contents of 0.02 and 0.001 weight per cent respectively or better can be attained provided the bath temperature is high, that is, in the vicinity of 80° C. Under optimum conditions the metallic impurity is extremely low.

PHENOL and a number of substituted phenols have strong tumour-promoting properties1, and similar activity has recently been demonstrated in a phenolic fraction of cigarette smoke (Salaman, M. H., and Roe, F. J. C., private communication). It seemed of interest, therefore, to record some results we have obtained in an examination of phenols from the smoke of a variety of British cigarettes.

DR. PRESTON, in his useful article on Zeeman's phenomenon in NATURE of the 5th inst., has expressed the opinion that some of the resolutions of spectral lines obtained by Michelson's interferometer are illusory (see p. 228). I had occasion some months ago to make use of some of Michelson's results, and came to the same conclusion. In fact, an instrumental resolution of what is in reality a single line may cause it to assume appearances, the principal of which are either a central line with faint appendage lines, or a double line with appendages.

THOUGH British workers have made some of the most signal contributions to the morphological aspects of zoology, and names like those of Romanes, Bateson, Doncaster, and Geoffrey Smith will always be distinguished for pioneer discoveries in the experimental field, Great Britain at the present moment compares very unfavourably with other countries in facilities for the publication of researches in experimental biology, especially on the zoological side. There is no single journal devoted wholly or mainly to the subject, with the exception of the Journal of Genetics, which of course only covers a portion of the field. We have in Great Britain nothing to compare, for example, with the Journal of Experimental Zoology, the Biological Bulletin, and the Journal of General Physiologyin America, or with the Archiv für Entwicklungsmechanikin Germany and the French Archives de morphologie expérimentale. Nor have we any biological journal which makes it a regular practice to publish articles of a general nature summarising and discussing critically recent additions to knowledge, as in the American Naturalistand the Referatenof several continental journals.

A SEVERE hailstorm occurred here yesterday evening, between 6 and 7 o'clock, and lasted for about a quarter of an hour. The hailstones being fairly large, I was able, by the aid of a good lens, to examine them somewhat carefully. The result of this examination I give shortly in the following statement.

THE intensities of 10 keV and 4 keV electrons have been measured from a sounding rocket launched into a post-breakup aurora. Pulsations in electron intensity were observed with a period of about 4 sec at both energies. The 10 keV pulsations occurred about half a second earlier than those at 4 keV. These results could have been caused by temporal changes in electron intensity and by a spatial structure in the path of the rocket because the causes are indistinguishable in the data. We treat the observed pulsations as temporal changes; they are similar in shape to pulsations observed in auroral light intensity, and electrons in the range 10 keV to 4 keV are important in the production of auroral light. If the pulsations are temporal in origin, the delay can be explained as a dispersion after simultaneous modulation 55,000 km from the rocket. The source of the modulation is found to be near the point where the local magnetic field line crosses the geomagnetic equator.

GOLDSTEIN1has shown that when two tones of frequency f1and f2(f2>f1) are heard simultaneously, the most prominent distortion product is the combination tone of frequency 2f1−f2. It is observed most strongly when the ratiof2/f1=1.1, when it is typically only 15 dB below the level of the primary tones. The relative amplitude can be measured by cancellation and is substantially independent of input level, that is, it can be considered as an essential non-linearity, but it decreases rapidly as the ratio f2/f1is increased. These features seem to rule out Helmholtz's2explanation based on simple limiting distortion in the middle ear.

AN important method of peptide sequence determination, namely mass spectrometry of N-methylated acyl peptides, has been described recently1,2. We devised the same method during studies of gastrin3, and have found that methylation by methyl iodide and silver oxide in dimethylformamide is not straightforward for residues of methionine, glutamic acid and aspartic acid. These more complex reactions, which involve the peptide backbone, do not prevent the method being used, but understanding of them is a prerequisite for its general application.