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Preventing SARS-CoV-2 infection by modulating viral host receptors, such as angiotensin-converting enzyme 2 (ACE2)1, could represent a new chemoprophylactic approach for COVID-19 that complements vaccination2,3. However, the mechanisms that control the expression of ACE2 remain unclear. Here we show that the farnesoid X receptor (FXR) is a direct regulator of ACE2 transcription in several tissues affected by COVID-19, including the gastrointestinal and respiratory systems. We then use the over-the-counter compound z-guggulsterone and the off-patent drug ursodeoxycholic acid (UDCA) to reduce FXR signalling and downregulate ACE2 in human lung, cholangiocyte and intestinal organoids and in the corresponding tissues in mice and hamsters. We show that the UDCA-mediated downregulation of ACE2 reduces susceptibility to SARS-CoV-2 infection in vitro, in vivo and in human lungs and livers perfused ex situ. Furthermore, we reveal that UDCA reduces the expression of ACE2 in the nasal epithelium in humans. Finally, we identify a correlation between UDCA treatment and positive clinical outcomes after SARS-CoV-2 infection using retrospective registry data, and confirm these findings in an independent validation cohort of recipients of liver transplants. In conclusion, we show that FXR has a role in controlling ACE2 expression and provide evidence that modulation of this pathway could be beneficial for reducing SARS-CoV-2 infection, paving the way for future clinical trials.

An assessment of the contribution of plant physiological effects to future changes in continental water runoff suggests that flooding risk under future global warming scenarios may be greater than was assumed. The stomatal pores that allow CO2 to enter plants and water to escape open less widely when CO2 concentrations are high, reducing water loss from the plant and thus leaving more water at the land surface. This effect may have contributed to the increase in continental runoff observed during the twentieth century, but most predictions of future changes in runoff don't account for it. The concept of 'CO2 equivalent', widely used to compare the effects of greenhouse gases on climate, does not account for this effect, so it may need to be revisited in light of these findings. An ensemble of experiments is used with a global climate model to assess the contribution of plant 'physiological forcing' to future changes in continental runoff. It is found that the effect increases simulated global mean runoff by 6 per cent when the concentration of carbon dioxide is doubled relative to pre-industrial levels; an increase that is comparable to that simulated in response to climate change caused by radiative forcing. This finding suggests that the risk of flooding may be greater than previously assumed under future global warming scenarios. In addition to influencing climatic conditions directly through radiative forcing, increasing carbon dioxide concentration influences the climate system through its effects on plant physiology1. Plant stomata generally open less widely under increased carbon dioxide concentration2, which reduces transpiration1,3,4,5,6 and thus leaves more water at the land surface7. This driver of change in the climate system, which we term ‘physiological forcing’, has been detected in observational records of increasing average continental runoff over the twentieth century8. Here we use an ensemble of experiments with a global climate model that includes a vegetation component to assess the contribution of physiological forcing to future changes in continental runoff, in the context of uncertainties in future precipitation. We find that the physiological effect of doubled carbon dioxide concentrations on plant transpiration increases simulated global mean runoff by 6 per cent relative to pre-industrial levels; an increase that is comparable to that simulated in response to radiatively forced climate change (11 ± 6 per cent). Assessments of the effect of increasing carbon dioxide concentrations on the hydrological cycle that only consider radiative forcing9,10,11 will therefore tend to underestimate future increases in runoff and overestimate decreases. This suggests that freshwater resources may be less limited than previously assumed under scenarios of future global warming, although there is still an increased risk of drought. Moreover, our results highlight that the practice of assessing the climate-forcing potential of all greenhouse gases in terms of their radiative forcing potential relative to carbon dioxide does not accurately reflect the relative effects of different greenhouse gases on freshwater resources.

Comprehensive global climate models1 are the only tools that account for the complex set of processes which will determine future climate change at both a global and regional level. Planners are typically faced with a wide range of predicted changes from different models of unknown relative quality2,3, owing to large but unquantified uncertainties in the modelling process4. Here we report a systematic attempt to determine the range of climate changes consistent with these uncertainties, based on a 53-member ensemble of model versions constructed by varying model parameters. We estimate a probability density function for the sensitivity of climate to a doubling of atmospheric carbon dioxide levels, and obtain a 5–95 per cent probability range of 2.4–5.4 °C. Our probability density function is constrained by objective estimates of the relative reliability of different model versions, the choice of model parameters that are varied and their uncertainty ranges, specified on the basis of expert advice. Our ensemble produces a range of regional changes much wider than indicated by traditional methods based on scaling the response patterns of an individual simulation5,6.

The thermohaline circulation of the ocean results primarily from downwelling at sites in the Nordic and Labrador Seas and upwelling throughout the rest of the ocean. The latter is often described as being due to breaking internal waves. Here we reconcile the difference between theoretical and observed estimates of vertical mixing in the deep ocean by presenting a revised view of the thermohaline circulation, which allows for additional upwelling in the Southern Ocean and the separation of the North Atlantic Deep Water cell from the Antarctic Bottom Water cell. The changes also mean that much less wind and tidal energy needs to be dissipated in the deep ocean than was originally thought.

When water is removed from DNA by semi-dehydration there is a pronounced effect on its in vivo activity, and the effect may be more severe in some regions of the chromosome than others. The effects of dehydration on the ability of cells to take part in recombination have been studied in three non-lysogenic strains of Escherichia coli K12.

The addition of inositol to the yeast Saccharomyces cerevisiae protects the yeast—when suspended in air—against death from desiccation, ultra-violet light and X-rays.

PREVIOUS work has established reasonably well that the reorientation or removal of water molecules bound to macromolecules may result in the loss of viability and infectivity of bacterial cells and virus particles1. During the above studies when auxotrophic cells were held at certain levels of relative humidity (RH), prototrophic mutants were found, apparently produced as a direct result of desiccation. Later the mutation of bacterial cells by ultra-violet light was found to be more easily achieved if the cells were partially desiccated at 40 per cent RH (ref. 2), indicating that bound water molecules played some part in the mechanisms responsible for mutation. Cells or virus particles held at RH levels between 80 and 30 per cent contain from 35 g water/100 g of cell solids (35 per cent water) to 3 per cent water1. Because 30–40 g water/100 g of solid is just sufficient to hydrate fully protein RNA and DNA, desiccation below 80 per cent RH affects only the quantity of bound water in the cell. The apparent mutation of cells from desiccation suggested that water molecules were, in part, responsible for maintaining the biological integrity of DNA, and therefore further studies were warranted. It is the purpose of this paper to present the results of preliminary investigations.

WAVELENGTHS of light between 320 and 400 nm are lethal to many microorganisms1, especially to airborne cells held in a semi-dehydrated state2–4. In addition, this waveband of light produces a few drug5 and phage6 resistant cells when growing cultures are continuously irradiated, and its mutagenic action is enhanced by cell semi-dehydration in aerosols3,4. We report here results which suggest that the irradiation of semi-dehydrated airborne cells with 320–400 nm light produces specific mutations.

IT has been shown1–7 that inositol will preserve the viability of bacterial cells and virus particles subjected to partial desiccation in aerosols. Previous experiments have shown also that the protective action of this compound relies on its ability to replace the water molecules removed from the microbe during desiccation. Since the microbe was found to die only when the water ‘bound’ to cell components was removed, it was suggested that hydrogen bonds formed between the cell components and water were largely responsible for maintaining the integrity of these components. Because of its structure, inositol was assumed to act as water during periods of desiccation and hence maintain the essential configuration of the cell components. Later investigations indicated that the cell component destroyed by desiccation was the ribonucleic acid and experiments with Rous sarcoma virus showed that inositol could protect this virus against inactivation during desiccation in aerosols.

ALUMINIUM succinate has been found as a massive deposit in a cavity in the heartwood of Cardwellia sublimis F. Muell. (Proteaceae), commonly known as northern silky oak or bull oak. This is a commercial timber tree restricted to the rain forests of tropical Queensland. The deposit occurred in a so-called ‘wind shake’ in a log from Jarra Creek near Tully, North Queensland. Inquiries from foresters and saw-millers indicate that such occurrences are rare. The log was about 10 ft. in girth, and the deposit apparently extended from the base to at least 25 ft. up the stem of the tree. A similar occurrence of aluminium succinate has been previously recorded1 in Orites excelsa R. Br. (Proteaceae), popularly known as silky oak or prickly ash, a timber tree of the subtropical rain forests of New South Wales. Basic aluminium succinate was also identified as a white deposit in the galleries of a longhorn beetle in timber of Qualea sp. (Vochysiaceae) from South America2.

IN recent years there has been a considerable interest in analytical methods for the determination of gases in metals, and there are numerous techniques available for this purpose, for example, vacuum fusion and hot-extraction methods; systems involving the 16O(n p)16N reaction, and others dependent on the liberation of the gases by means of a d.c. arc followed by gas chromatographic or spectrographic measurements.

RECENTLY S. J. W. and Dodds reported that 136 GHz microwaves interfere with the growth of Escherichia coli cells1. Here we report further investigations of the absorption of 65 to 75 GHz microwaves by cells of E. coli BR as well as isolated protein, RNA and DNA, and its effect on some metabolic processes. Our equipment has been described1,2. Cells were grown for 24 h at 37° C in nutrient broth (NB) and either (a) washed twice in 0.85 per cent NaCl and deposited as a pellet by centrifugation or (b) resuspended after washing to a cell concentration of 1 × 106 cells/ml. in 0.5 per cent glucose + 0.5 per cent casamino-acids + 50 µg/ml. thymine in 0.1 M phosphate buffer, pH 6.9 (GCT). To examine the effect of microwaves on cell growth, 0.5 ml. aliquots of cells suspended in GCT were placed in vials 1.5 cm in diameter. Some vials were put on top of microwave horns and others incubated at the same temperature (25° C) out of the radiation field. At various times the vials were removed and the number of cells/ml. determined by dilution and plating on nutrient agar. The effect of microwave absorption on metabolic processes was investigated by resuspending the washed cells to a concentration of 1 × 108 cells/ml. in 1.0 per cent glucose in 0.1 M phosphate buffer, pH 6.9. Aliquots of 0.2 ml. of this suspension were placed in the vials and after positioning on the microwave apparatus 0.3 ml. of a solution was added, which contained 0.8 µCi/ml. of one of the following: thymine-2-14C, uracil-2-14C or algal 14C protein hydrolysateplus two of the following: unlabelled thymine, 50 µg/ml.; uracil, 100 µg/ml.; or casamino-acids, 500 µg/ml. After various times the cells from each vial were deposited onto a Millipore filter and washed with 100 ml. of 1 N HCl; the filter was dried and radioactivity counted. The microwave absorption spectra of the cells, H2O, protein, RNA and DNA were obtained by making films of the material on a thin mica window. The films were dried at 80 per cent relative humidity and covered with a second thin piece of mica. The difference between the microwave absorption of a blank and the film gave the absorption spectrum of the film of cells or biological material.

DURING investigations into the effects of dehydration on airborne cells, a millimetre microwave spectrometer, built to measure the quantity of water present in airborne cells, revealed that microwaves had an effect on cell metabolism. We report here some preliminary findings.

FAILURE of Araucaria cunninghamii Sweet, to regenerate in secondary rain-forest dominated by Backhousia angustifolia F. Muell. has been observed near Maryborough, Queensland. A plausible explanation of this observation appeared to lie in the widely discussed possibility1 that a plant may interfere with the establishment of adjacent species in a natural community by releasing ‘antibiotics’, either from living roots or from decomposing surface debris.

IN certain tribes of the family Rutaceae a relatively high proportion of species has been found to contain alkaloids. Moreover, these alkaloids vary widely in character and include representatives of several of the principal structural groups, for example, quinoline, iso-quinoline, carboline and imidazole derivatives.

TSETSE have been successfully marked, so that they can be located at night, with paints which fluoresce in ultra-violet light1 (see Jewell, preceding communication), but the method had the disadvantage that the equipment required to produce ultra-violet light in the field was cumbersome. It was considered that the reflecting paints, nowadays widely used for road signs, might be equally effective for marking the insects and require only light in the ordinary visual range, such as can be provided by an electric torch.

IT would be difficult to find two books more unlike than these in method and, as it appears to us, in value. We may, though we very seldom do, disagree with Sir Thomas Heaths interpretation of the evidence that he produces, but there is no denying that the evidence exists. Mr. Menons brilliant imaginative work we can only regard as a fabric of guess-work erected upon a substructure of dreams. (1) Greek Astronomy. By Sir Thomas L. Heath. (The Library of Greek Thought.) Pp. lvii + 192. (London and Toronto: J. M. Dent and Sons, Ltd.; New York: E. P. Dutton and Co., 1932.) 5s. net. (2) Early Astronomy and Cosmology: a Reconstruction of the Earliest Cosmic System. By C. P. S. Menon. Pp. 192. (London: George Allen and Unwin, Ltd., 1932.) 10s. net.

The Dynamics of the Upper Ocean. (Second edition.) By O. M. Phillips. Pp. 336. (Cambridge University: Cambridge, London and New York, 1977.) £16.

Diospyros hebecarpa A. Cunn. is a small or medium tree which is common on the tropical coast of Queensland and has been suspected of poisoning livestock1. As other Diospyros species are reported to contain plumbagin2, it seemed possible that this is the toxic substance in D. hebecarpa. We have found that plumbagin is present in the leaves and bark of this species, and in addition we have isolated from the fresh leaves and immature fruits a new colourless crystalline compound, melting point 112−113° C., with the composition C11H10O3. In chemical properties and absorption spectrum this substance closely resembles β-hydrojuglone and β-hydroplumbagin, which are also colourless when pure. On oxidation with ferric chloride it gives a quinone, melting point 125–126° C. (‘Pyrex’), which is an isomer of plumbagin. (This quinone melts with decomposition at a much lower temperature in soda glass. Juglone behaves similarly, and its melting point may be raised to 164–165° C. in ‘Pyrex’ glass.)

THE “age of the tide” is a measure of the time lag between new or full Moon and the following spring tide. In the Coral Sea, the age of the tide is negative1. This behaviour is rare in the ocean. In terms of the tidal response function this means that there is a negative phase change in the R−22 (ω) response function2, between the frequencies of the dominant M2 and S2 constituents.

A SYSTEMATIC survey of Australian plants for alkaloids, begun in 1944 by the Division of Plant Industry, Commonwealth Scientific and Industrial Research Organisation, has already involved the testing of several thousand species for alkaloids and other compounds of possible chemical or pharmacological interest. Most of these tests were done in the field on fresh samples of bark, leaves, roots, wood or fruits.

MAY I point out that your reviewer of “Ptolemy's Catalogue of Stars” (June 1, p. 282) is mistaken in suggesting that a mere confusion between the uncial alpha (=1) and the uncial delta (=4) will account for Ptolemy's assignment of the first magnitude to what is now the third-magnitude star,θ Eridani?