Search

A defining pathological feature of most neurodegenerative diseases is the assembly of proteins into amyloid that form disease-specific structures1. In Alzheimer’s disease, this is characterized by the deposition of β-amyloid and tau with disease-specific conformations. The in situ structure of amyloid in the human brain is unknown. Here, using cryo-fluorescence microscopy-targeted cryo-sectioning, cryo-focused ion beam-scanning electron microscopy lift-out and cryo-electron tomography, we determined in-tissue architectures of β-amyloid and tau pathology in a postmortem Alzheimer’s disease donor brain. β-amyloid plaques contained a mixture of fibrils, some of which were branched, and protofilaments, arranged in parallel arrays and lattice-like structures. Extracellular vesicles and cuboidal particles defined the non-amyloid constituents of β-amyloid plaques. By contrast, tau inclusions formed parallel clusters of unbranched filaments. Subtomogram averaging a cluster of 136 tau filaments in a single tomogram revealed the polypeptide backbone conformation and filament polarity orientation of paired helical filaments within tissue. Filaments within most clusters were similar to each other, but were different between clusters, showing amyloid heterogeneity that is spatially organized by subcellular location. The in situ structural approaches outlined here for human donor tissues have applications to a broad range of neurodegenerative diseases.

Hospital-based transmission had a dominant role in Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV) epidemics1,2, but large-scale studies of its role in the SARS-CoV-2 pandemic are lacking. Such transmission risks spreading the virus to the most vulnerable individuals and can have wider-scale impacts through hospital–community interactions. Using data from acute hospitals in England, we quantify within-hospital transmission, evaluate likely pathways of spread and factors associated with heightened transmission risk, and explore the wider dynamical consequences. We estimate that between June 2020 and March 2021 between 95,000 and 167,000 inpatients acquired SARS-CoV-2 in hospitals (1% to 2% of all hospital admissions in this period). Analysis of time series data provided evidence that patients who themselves acquired SARS-CoV-2 infection in hospital were the main sources of transmission to other patients. Increased transmission to inpatients was associated with hospitals having fewer single rooms and lower heated volume per bed. Moreover, we show that reducing hospital transmission could substantially enhance the efficiency of punctuated lockdown measures in suppressing community transmission. These findings reveal the previously unrecognized scale of hospital transmission, have direct implications for targeting of hospital control measures and highlight the need to design hospitals better equipped to limit the transmission of future high-consequence pathogens.

The history of the British Isles and Ireland is characterized by multiple periods of major cultural change, including the influential transformation after the end of Roman rule, which precipitated shifts in language, settlement patterns and material culture1. The extent to which migration from continental Europe mediated these transitions is a matter of long-standing debate2–4. Here we study genome-wide ancient DNA from 460 medieval northwestern Europeans—including 278 individuals from England—alongside archaeological data, to infer contemporary population dynamics. We identify a substantial increase of continental northern European ancestry in early medieval England, which is closely related to the early medieval and present-day inhabitants of Germany and Denmark, implying large-scale substantial migration across the North Sea into Britain during the Early Middle Ages. As a result, the individuals who we analysed from eastern England derived up to 76% of their ancestry from the continental North Sea zone, albeit with substantial regional variation and heterogeneity within sites. We show that women with immigrant ancestry were more often furnished with grave goods than women with local ancestry, whereas men with weapons were as likely not to be of immigrant ancestry. A comparison with present-day Britain indicates that subsequent demographic events reduced the fraction of continental northern European ancestry while introducing further ancestry components into the English gene pool, including substantial southwestern European ancestry most closely related to that seen in Iron Age France5,6.

Any system of coupled oscillators may be characterized by its spectrum of resonance frequencies (or eigenfrequencies), which can be tuned by varying the system’s parameters. The relationship between control parameters and the eigenfrequency spectrum is central to a range of applications1–3. However, fundamental aspects of this relationship remain poorly understood. For example, if the controls are varied along a path that returns to its starting point (that is, around a ‘loop’), the system’s spectrum must return to itself. In systems that are Hermitian (that is, lossless and reciprocal), this process is trivial and each resonance frequency returns to its original value. However, in non-Hermitian systems, where the eigenfrequencies are complex, the spectrum may return to itself in a topologically non-trivial manner, a phenomenon known as spectral flow. The spectral flow is determined by how the control loop encircles degeneracies, and this relationship is well understood for N=2(where Nis the number of oscillators in the system)4,5. Here we extend this description to arbitrary N. We show that control loops generically produce braids of eigenfrequencies, and for N>2these braids form a non-Abelian group that reflects the non-trivial geometry of the space of degeneracies. We demonstrate these features experimentally for N=3using a cavity optomechanical system.

In the past two decades, high-amplitude electromagnetic outbursts have been detected from dormant galaxies and often attributed to the tidal disruption of a star by the central black hole1,2. X-ray emission from the Seyfert 2 galaxy GSN 069 (2MASX J01190869-3411305) at a redshift of z= 0.018 was first detected in July 2010 and implies an X-ray brightening by a factor of more than 240 over ROSAT observations performed 16 years earlier3,4. The emission has smoothly decayed over time since 2010, possibly indicating a long-lived tidal disruption event5. The X-ray spectrum is ultra-soft and can be described by accretion disk emission with luminosity proportional to the fourth power of the disk temperature during long-term evolution. Here we report observations of quasi-periodic X-ray eruptions from the nucleus of GSN 069 over the course of 54 days, from December 2018 onwards. During these eruptions, the X-ray count rate increases by up to two orders of magnitude with an event duration of just over an hour and a recurrence time of about nine hours. These eruptions are associated with fast spectral transitions between a cold and a warm phase in the accretion flow around a low-mass black hole (of approximately 4 × 105solar masses) with peak X-ray luminosity of about 5 × 1042erg per second. The warm phase has kT(where Tis the temperature and kis the Boltzmann constant) of about 120 electronvolts, reminiscent of the typical soft-X-ray excess, an almost universal thermal-like feature in the X-ray spectra of luminous active nuclei6–8. If the observed properties are not unique to GSN 069, and assuming standard scaling of timescales with black hole mass and accretion properties, typical active galactic nuclei with higher-mass black holes can be expected to exhibit high-amplitude optical to X-ray variability on timescales as short as months or years9.

Visceral leishmaniasis causes considerable mortality and morbidity in many parts of the world. There is an urgent need for the development of new, effective treatments for this disease. Here we describe the development of an anti-leishmanial drug-like chemical series based on a pyrazolopyrimidine scaffold. The leading compound from this series (7, DDD853651/GSK3186899) is efficacious in a mouse model of visceral leishmaniasis, has suitable physicochemical, pharmacokinetic and toxicological properties for further development, and has been declared a preclinical candidate. Detailed mode-of-action studies indicate that compounds from this series act principally by inhibiting the parasite cdc-2-related kinase 12 (CRK12), thus defining a druggable target for visceral leishmaniasis.

We have recently presented evidence1supporting the hypothesis2that the long-lived large oval atmospheric eddies on Jupiter and Saturn, including Jupiter's anticyclonic Great Red Spot (GRS) and White Ovals and the cyclonic ‘barges’, are manifestations of ‘slantwise’ or ‘sloping’ convection in a rotating fluid, implying that they are involved in the horizontal transport of heat towards or away from the edges of the atmospheric zones or belts in which they occur, and that their kinetic energy derives directly from the action of gravity on the density field associated with horizontal gradients of temperature. These eddies would then be dynamically similar to the highly stable closed ‘baroclinic’ eddies produced in certain laboratory experiments on thermal convection in a rotating fluid subject to internal heating or cooling1,3. We now present laboratory findings that bear on the interpretation of the isolated nature of the GRS, including the crucial demonstration that a single intense stable baroclinic disturbance that is strongly localized in azimuth can form readily when the impressed conditions are close to the transition from axisymmetric to non-axisymmetric flow.

Mycorrhizal infection of plants in many natural vegetation systems arises when uninfected roots make contact with mycelia spreading from infected roots1,2. The result of the infection is that connections are present between the roots of individual plants. It has been shown by autoradiography that these interconnections provide a direct pathway for the transfer of carbon between ecto-mycorrhizal plants2,3. Inter-plant transfer of carbon4and phosphorus5–7has been reported in plants with vesicular–arbuscular (VA) mycorrhizas, but in the absence of comparable evidence it remains a possibility that in these cases the pathway is indirect, uptake by the fungus of the ‘receiver’ plant occurring only after leakage of the nutrients from roots of the ‘donor’. We now show using autoradiography that transfer of carbon between plants connected by VA mycorrhizal mycelium occurs primarily by the direct hyphal pathway. It is further shown that the magnitude of the transfer is strongly influenced by shading of ‘receiver’ plants indicating that movement is governed by source–sink relationships.

The Great Red Spot (GRS), the three White Ovals, and other long-lived anticyclonic eddies in Jupiter's atmosphere might be dynamically similar1to the closed, stable baroclinic eddies that were first discovered in laboratory studies of thermal convection in a rotating fluid subject to internal heating and sidewall cooling2,3. We outline here results of new laboratory and numerical experiments on the structure, energetics and stability of such eddies, which strongly support the suggestion that these laboratory and atmospheric flows (including similar eddies found on Saturn4) might all be manifestations of the same dynamical process—‘sloping’ or ‘slantwise’ convection. Included in our numerical experiments are cases with internal cooling and sidewall heating, in which stable baroclinic eddies with a cyclonic peripheral jet stream at upper levels surrounding a region of slow descent have been produced and studied. We suggest that these cyclonic eddies are dynamically similar to the ‘barges’ observed in Jupiter's Tropical and Temperate Belts5.

Darwin1proposed that secondary sexual characters, such as the long tails and bright plumage of many birds, evolved because females use them as cues in male choice. The question of why females should prefer males with such apparently deleterious characters is currently the subject of vigorous debate2–7. Hamilton and Zuk8suggest that females use secondary sexual characters to assess a male's ability to resist parasites. A prediction of this hypothesis is that male brightness should correlate positively with parasite load across species, and the only evidence advanced in support of the model is Hamilton and Zuk's8finding that such a correlation exists across North American passerines. But interspecific correlations of this sort can result from phylogenetic associations through common descent or from independent associations with some confounding variable, such as an aspect of behaviour or ecology9–13. Here, I use data on European passerines and an enlarged data set on North American passerines to demonstrate positive relationships between male brightness and parasite prevalence which remain when the effects of taxonomic, behavioural and ecological variables are removed.

Although studies of-the biology of mycorrhizas have repeatedly demonstrated their capacity to enhance nutrient capture in circumstances where essential elements are present in growth limiting quantities1–3, knowledge of their function in environments containing potentially toxic concentrations of metallic elements is lacking. It is known that mycorrhizal infection can increase the uptake of copper and zinc from soil solutions containing low concentrations of these metals4, but any such increase in circumstances of high metal concentration would clearly be disadvantageous. Because of the large number of situations, both natural and man-made, in which heavy metal toxicity can restrict plant growth, it is of great ecological and applied interest to increase our understanding of those factors which permit growth of plants on heavily contaminated soils. One of the most successful colonists of such soils in northern Europe is the strongly mycorrhizal ericaceous plant Calluna vulgaris5. Calluna has a characteristic ‘ericoid’ mycorrhizal infection which, in contrast to the situation found in vesicular-arbuscular (VA) mycorrhizas, has been shown primarily to enhance nitrogen rather than phosphorus uptake6,7. We have examined the possibility that mycorrhizal infection may influence the resistance of Calluna to high levels of heavy metals. The growth, survival and heavy metal content of two races of Calluna, one from a metal-polluted site and one from an unpolluted natural heathland, have been compared when plants were grown in the mycorrhizal (M) and non-mycorrhizal (NM) condition in sand cultures supplemented with different levels of copper and zinc. We report here that whereas NM plants show no tolerance of these metals at high concentrations, mycorrhizal infection provides a major degree of resistance to the toxicity and that infection leads to significant reduction of the heavy metal content of the shoot.

Anastomosing systems of fungal rhizomorphs are found in association with mycorrhizal roots of trees in arid zones1, in soils of temperate deciduous2, coniferous3and humid tropical4forests, and even in mine spoils5. Although it is recognized that the fungus depends on the host for its carbon supply6,7, the functional relationship between the partners has not been investigated fully. Transport of 32P through rhizomorphs has been demonstrated8, but their potential to absorb and transport water is not known. We have synthesized mycorrhizal rhizomorphs in association with pine, and preliminary experiments with tritiated water (3H2O) showed that the cut distal ends could absorb water which was transported to mycorrhizal roots and to seedling needles9. We have since developed a method for feeding 3H2O to the intact terminal portions of rhizomorphs in sealed vessels with negligible disturbance to the mycelial system, and we report here that mycorrhizal rhizomorphs can absorb water and facilitate its transport over ecologically significant distances. Electron microscopy shows that the rhizomorphs are differentiated structures with large central ‘vessel’ hyphae.

Strong SiO masers occur in the inner regions of the stellar envelopes (within a few stellar radii) of variable late-type stars (Miras, semi-regular variables and supergiants), and in the vicinity of IRc2 in Orion, a site of recent star formation. Although linear polarization is a common feature of these masers1–3, previous attempts to detect circular polarization have been inconclusive. Johnson and Clark4claimed detection of 10–20% polarization in Stokes V (left-hand circular minus right-hand circular) spectra of the Orion masers at 86.2 GHz. Troland et al.1failed to confirm this result, while reporting small signals in Stokes V spectra for several sources which they attributed to instrumental effects. Here we report sensitive measurements of circular polarization in SiO masers associated with late-type stars, which reveal significantly polarized features at the several per cent level in five of six stars observed. Under the Zeeman splitting hypothesis, these measurements imply magnetic fields in the masing gas in the range 10–100 G. The masers associated with IRc2 in the Orion-KL region were not detected in circular polarization.

Most investigations of floristic diversity have involved studies1–15of natural vegetation. Progress using these approaches has been limited because some potentially important factors are not amenable to precise field measurement or manipulation. Here we describe an alternative research strategy in which communities were allowed to develop in turf microcosms providing factorial combinations of soil heterogeneity, grazing and mycorrhizal infection, all of which are capable in theory6,10,13,16–19of promoting diversity. Both grazing and mycorrhizas increased diversity markedly by raising the biomass of the subordinate species relative to that of the canopy dominant. The effect of grazing is shown to be due to the differential sensitivity of the canopy dominant to defoliation. Export of assimilate from canopy to subordinate species through a common mycelial network is likely, together with enhancement of mineral nutrient capture, to be involved in the beneficial effect of mycorrhizas. No major effects of soil heterogeneity upon diversity were detected.

TO write an account of the development of chemistry during the last hundred years is a task which might well daunt even the boldest spirit ; for chemistry is a major science advancing rapidly on an ever-widening front, and the period in question begins not long after chemistry had become an exact science capable of mathematical interpretation. The infusion into the body of science of a new spirit—an achievement which, in Liebig's words, constituted the immortal glory of Lavoisier—led rapidly to the formulation of that comprehensive Atomic Theory the ramifications of which form the nervous system of the wonderful body of physical science as we know it to-day.

PROF. SIR DAVID ORME MASSON, who died at Melbourne on August 10, was born at Hampstead, London, on January 13, 1858. He was of mixed English and Scots descent. His father, Prof. David Masson, editor of Milton, Goldsmith and De Quincey, and Historiographer-Royal for Scotland, came of Aberdeenshire stock—there is a saying in the Don valley that "Eassons, Massons an' Kessons a' cam' frae Tarlandside". His mother, Rosaline Orme, had a forbear George Rutt, the father of Joseph Priestley's biographer, John Towill Rutt ; and it may be mentioned, as throwing some light on the family, that the home of the Ormes, in Avenue Road, Hampstead, was a favourite rallying ground of the Pre-Raphaelites. In 1865 David Masson migrated from the chair of English literature at University College, London, to the Regius chair of English in the University of Edinburgh, and so it came about that his son, David Orme Masson, was educated at Edinburgh Academy and afterwards graduated M.A. and B.Sc. at Edinburgh.

ENGLISH scholars first became interested in the translation of alchemical texts in the twelfth century, when they participated with the celebrated Gerard of Cremona and other continental scholars in making known to western Europe the accumulated wisdom of the Muslim world. Prominent among them were Adelard of Bath, Walcher of Malvern, Roger of Hereford, and Robert of Chester, the last-named of whom, according to tradition, first introduced chemistry into Europe. “Since,” wrote Robert, in the preface to his first translation of an Arabic alchemical treatise, in 1144, “your Latin world does not yet know what alchemy is, I will explain in the present book.” The translations of this period were of course done into Latin, and the same language was the usual medium in which the adepts embodied, or embedded, their observations and ideas throughout the succeeding five centuries.

SEISMIC interpretation at the University of Tasmania has been enhanced by using very-low-speed magnetic tape recordings in conjunction with the normal pen recordings. When played back with a time compression of 250, the outputs from the short period ‘Willmore’ seismometers become audible. By comparing the tape and the pen recordings for earthquakes easily identifiable on the pen recordings it has been found, once the various tones are memorized, that it is not only possible to hear seismic activity which is lost in background noise on the pen records, but also to tell approximately the region from which they originated. Since a 2,400 ft. reel of 0.25 in. magnetic tape lasts approximately 3 months if used continuously, this slow-speed recording also affords an economical way of permanently storing the records in an electrical form.

FOR a long period Alfred Werner's classical “Lehrbuch der Stereochemie”(1904) held undisputed sway as the standard work on this branch of science. With the passage of time, and more particularly during the last few years, the need has become manifest for a fresh and up-to-date treatment of a rapidly expanding field of science which now claims the interested attention of chemist and physicist alike. Accordingly, several books dealing with the subject of spatial chemistry have appeared lately in rapid succession. None of them can be held to be entirely satisfying.A glance at the list of contents of Prof. Gold-schmidt's volume conveys the impression that he has fully covered his extensive field. There are sections on the stereochemistry of carbon, nitrogen and other elements; optical rotatory power and chemical constitution; and spatial configuration and reaction-velocity; while Dr. R. Bloch contributes a concluding section on the relationships existing between stereochemistry and crystallography. It may be said at once that the major part of the book can be read with pleasure and profit, and that it constitutes a useful contribution to the literature of stereochemistry.

PROF. H. RUPE entered the private laboratory at Munich, as assistant to Baeyer, in 1891. At that date the great indigo problem had been solved, but the classical work on the reduction of the phthalic acids was still in full swing. These investigations, so well known in the abstract because of their bearing upon the constitution of benzene, take on at once a rich vesture of human interest to the reader of Prof. Rupe's delightful reminiscences of life in Baeyer's laboratory which have recently been published*. The work was beset with difficulties. At one time, for example, during the intensive search for dihydrophthalic acids, gigantic quantities of sodium amalgam, up to forty kilograms a week, were prepared and used in vain. The author remarks with feeling that the situation became very disagreeable to the assistants. It must have been, indeed, a “schwere, scheussliche und gefahrliche Arbeit”; but no labour was too tedious for the Master and his band of devoted helpers. There was, as Prof.Rupe says, something of the magnificent in this prolonged contest with matter.

COMMUNICATIONS upon the subject of Chinese alchemy have appeared several times in NATURE during the past year by Prof. J. R. Partington and have greatly interested me. The Pent'sao and similar books upon Chinese mineral drugs make repeated reference to the transmutation of metals into gold. However, few of these books have very old editions extant, so I have been looking up the subject of alchemy from other sources.

EXTENSIVE investigations have been carried out on the effects of radiation on various organic polymers assuming that they could be regarded as model compounds for biological materials. Our previous work concerning the effects of gamma-rays on aqueous polymer solutions1–3revealed the existence of new effects resulting from the presence of water. Radiation-induced changes in the polymer may result either from the direct effect of the radiation on the solute molecules or from the indirect effect, that is, reactions of solute with reactive species such as hydrogen atoms, hydroxyl radicals or solvated electrons produced by irradiation of the water. The indirect effect becomes increasingly important as the concentration is reduced4.