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The serious threats posed by drug-resistant bacterial infections and recent developments in synthetic biology have fueled a growing interest in genetically engineered phages with therapeutic potential. To date, many investigations on engineered phages have been limited to proof of concept or fundamental studies using phages with relatively small genomes or commercially available “phage display kits”. Moreover, safeguards supporting efficient translation for practical use have not been implemented. Here, we developed a cell-free phage engineering and rebooting platform. We successfully assembled natural, designer, and chemically synthesized genomes and rebooted functional phages infecting gram-negative bacteria and acid-fast mycobacteria. Furthermore, we demonstrated the creation of biologically contained phages for the treatment of bacterial infections. These synthetic biocontained phages exhibited similar properties to those of a parent phage against lethal sepsis in vivo. This efficient, flexible, and rational approach will serve to accelerate phage biology studies and can be used for many practical applications, including phage therapy.

Globally equitable access to safely managed drinking water and sanitation is one of the major aims of the United Nations’ Sustainable Development Goals, specifically SDG goal 6. We assessed global-scale progress toward this goal from 2000 to 2020 with access rates to improved drinking water and sanitation services that are adjusted for socioeconomic, political, and hydrological conditions. We found that the adjusted access rates in 2020 were lower than 2000, although not-adjusted access rates had increased. Access rates improved more slowly in higher-GDP countries than in lower-GDP ones during this period. These show that access rates in lower-income countries improved, but were still lower, compared with those in countries with the same social conditions in 2000. This suggests the recent progress toward this goal has not aligned well with social development, emphasizing need for reflecting national management, international cooperation, and investment in water-related infrastructures to achieve the goal by 2030.

We present distributions of the zonal-mean temperature and static stability in the Venusian atmosphere obtained from Venus Express and Akatsuki radio occultation profiles penetrating down to an altitude of 40 km. At latitudes equatorward of 75°, static stability derived from the observed temperature profiles is consistent with previous in-situ measurements in that there is a low-stability layer at altitudes of 50–58 km and highly and moderately stratified layers above 58 km and below 50 km, respectively. Meanwhile, at latitudes poleward of 75°, a low-stability layer extends down to 42 km, which has been unreported in analyses of previous measurements. The deep low-stability layer in the polar region cannot be explained by vertical convection in the middle/lower cloud layer, and the present result thus introduces new constraints on the dynamics of the sub-cloud atmosphere. The Venusian atmosphere is in striking contrast to the Earth’s troposphere, which generally has a deeper low-stability layer at low latitudes than at mid- and high latitudes.

Key messageThe GAF1 transcription factor is shown to bind to the promoter of the Arabidopsis GA-biosynthetic enzyme GA20ox1 and, in association with DELLA protein, promotes GA20ox1 expression, thereby contributing to its feedback regulation and tissue specificity.Gibberellins (GAs) are phytohormones that promote plant growth and development, including germination, elongation, flowering, and floral development. Homeostasis of endogenous GA levels is controlled by GA feedback regulation. DELLAs are negative regulators of GA signaling that are rapidly degraded in the presence of GAs. DELLAs regulate several target genes, including AtGA20ox2 and AtGA3ox1, encoding the GA-biosynthetic enzymes GA 20-oxidase and GA 3-oxidase, respectively. Previous studies have identified GAI-ASSOCIATED FACTOR 1 (GAF1) as a DELLA interactor, with which DELLAs act as transcriptional coactivators; furthermore, AtGA20ox2, AtGA3ox1, and AtGID1b were identified as target genes of the DELLA-GAF1 complex. Among the five Arabidopsis GA20ox genes, AtGA20ox1 is the most highly expressed gene during vegetative growth; its expression is controlled by GA feedback regulation. Here, we investigated whether AtGA20ox1 is regulated by the DELLA-GAF1 complex. The electrophoretic mobility shift and transactivation assays showed that three GAF1-binding sites exist in the AtGA20ox1 promoter. Using transgenic plants, we further evaluated the contribution of the DELLA-GAF1 complex to GA feedback regulation and tissue-specific expression. Mutations in two GAF1-binding sites obliterated the negative feedback regulation and tissue-specific expression of AtGA20ox1 in transgenic plants. Thus, our results showed that GAF1-binding sites are involved in GA feedback regulation and tissue-specific expression of AtGA20ox1 in Arabidopsis, suggesting that the DELLA-GAF1 complex is involved in both processes.

The bacterium Staphylococcus aureus, which colonizes healthy human skin, may cause diseases, such as atopic dermatitis (AD). Treatment for such AD cases involves antibiotic use; however, alternate treatments are preferred owing to the development of antimicrobial resistance. This study aimed to characterize the novel bacteriophage SaGU1 as a potential agent for phage therapy to treat S. aureus infections. SaGU1 that infects S. aureus strains previously isolated from the skin of patients with AD was screened from sewage samples in Gifu, Japan. Its genome was sequenced and analyzed using bioinformatics tools, and the morphology, lytic activity, stability, and host range of the phage were determined. The SaGU1 genome was 140,909 bp with an average GC content of 30.2%. The viral chromosome contained 225 putative protein-coding genes and four tRNA genes, carrying neither toxic nor antibiotic resistance genes. Electron microscopy analysis revealed that SaGU1 belongs to the Myoviridae family. Stability tests showed that SaGU1 was heat-stable under physiological and acidic conditions. Host range testing revealed that SaGU1 can infect a broad range of S. aureus clinical isolates present on the skin of AD patients, whereas it did not kill strains of Staphylococcus epidermidis, which are symbiotic resident bacteria on human skin. Hence, our data suggest that SaGU1 is a potential candidate for developing a phage therapy to treat AD caused by pathogenic S. aureus.

Atopic dermatitis is accompanied by the abnormal overgrowth of Staphylococcus aureus, a common cause of skin infections and an opportunistic pathogen. Although administration of antibiotics is effective against S. aureus, the resulting reduction in healthy microbiota and the emergence of drug-resistant bacteria are of concern. We propose that phage therapy can be an effective strategy to treat atopic dermatitis without perturbing the microbiota structure. In this study, we examined whether the S. aureus phage SaGU1 could be a tool to counteract the atopic exacerbation induced by S. aureus using an atopic mouse model. Administration of SaGU1 to the back skin of mice reduced both S. aureus counts and the disease exacerbation caused by S. aureus. Furthermore, the S. aureus-mediated exacerbation of atopic dermatitis with respect to IgE plasma concentration and histopathological findings was ameliorated by the application of SaGU1. We also found that Staphylococcus epidermidis, a typical epidermal symbiont in healthy skin, significantly attenuated the emergence of SaGU1-resistant S. aureus under co-culture with S. aureus and S. epidermidis in liquid culture infection experiments. Our results suggest that phage therapy using SaGU1 could be a promising clinical treatment for atopic dermatitis.

Unlike the polar vortices observed in the Earth, Mars and Titan atmospheres, the observed Venus polar vortex is warmer than the midlatitudes at cloud-top levels (∼65 km). This warm polar vortex is zonally surrounded by a cold latitude band located at ∼60° latitude, which is a unique feature called ‘cold collar’ in the Venus atmosphere. Although these structures have been observed in numerous previous observations, the formation mechanism is still unknown. Here we perform numerical simulations of the Venus atmospheric circulation using a general circulation model, and succeed in reproducing these puzzling features in close agreement with the observations. The cold collar and warm polar region are attributed to the residual mean meridional circulation enhanced by the thermal tide. The present results strongly suggest that the thermal tide is crucial for the structure of the Venus upper polar atmosphere at and above cloud levels. Unlike some planets, the Venusian polar vortex is warmer than the mid-latitudes at cloud-top level, but the mechanism behind this is unknown. Here, the authors use a general circulation model and suggest the cold collar and warm polar regions are due to residual mean meridional circulation intensified by thermal tides.

Background Feeding and eating disorders are severe mental disorders that gravely affect patients’ lives. In particular, patients with anorexia nervosa (AN) or bulimia nervosa (BN) appear to have poor social cognition. Many studies have shown the relationship between poor social cognition and brain responses in AN. However, few studies have examined the relationship between social cognition and BN. Therefore, we examined which brain regions impact the ability for social cognition in patients with BN. Methods We used task-based functional magnetic resonance imaging (fMRI) to examine brain responses during a social cognition task and the Reading Mind in the Eyes Test (RMET). During the fMRI, 22 women with BN and 22 healthy women (HW) took the RMET. Participants also completed the eating disorder clinical measures Bulimic Investigatory Test, Edinburgh (BITE) and Eating Disorders Examination Questionnaire (EDE-Q), the Patient Health Questionnaire (PHQ-9) measure of depression; and the Generalized Anxiety Disorder (GAD-7) measure of anxiety. Results No difference was observed in the RMET scores between women with BN and HW. Both groups showed activation in brain regions specific to social cognition. During the task, no differences were shown between the groups in the BOLD signal ( p  < 0.05, familywise error corrected for multiple comparisons). However, there was a tendency of more robust activation in the right angular gyrus, ventral diencephalon, thalamus proper, temporal pole, and middle temporal gyrus in BN ( p  < 0.001, uncorrected for multiple comparisons). Moreover, HW showed a positive correlation between RMET scores and the activation of two regions: medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC); however, no significant correlation was observed in women with BN. Conclusions While activation in the mPFC and ACC positively correlated to the RMET scores in HW, no correlation was observed in BN patients. Therefore, women with BN might display modulated neural processing when thinking of others’ mental states. Further examination is needed to investigate neural processing in BN patients to better understand their social cognition abilities. Trial registration UMIN, UMIN000010220. Registered 13 March 2013, https://rctportal.niph.go.jp/s/detail/um?trial_id=UMIN000010220

Impacts of temperature assimilation on the Venus atmosphere are investigated by the observing system simulation experiments assuming cross-link radio occultation measurements of the Venus atmosphere (CROVA). Synthetic temperature data are prepared by a Venusian general circulation model (VGCM) with 80% of the solar heating to produce a weaker super-rotation than the default model would. Observational points of radio occultation measurements are realistically determined by a pair of satellites with feasible orbits. Then the vertical temperature profiles in 40–90 km altitudes at those points are assimilated into the original VGCM where the faster super-rotation is reproduced. The results show that the three-dimensional structure of the true atmosphere could be significantly improved not only in temperature but also in horizontal winds, when temperature observations are available with more than 40 points per day using 3 small cube satellites for 30 days. It would be promising to plan CROVA mission for future.

The ultraviolet imager (UVI) has been developed for the Akatsuki spacecraft (Venus Climate Orbiter mission). The UVI takes ultraviolet (UV) images of the solar radiation reflected by the Venusian clouds with narrow bandpass filters centered at the 283 and 365 nm wavelengths. There are absorption bands of SO2 and unknown absorbers in these wavelength regions. The UV images provide the spatial distribution of SO2 and the unknown absorber around cloud top altitudes. The images also allow us to understand the cloud top morphologies and haze properties. Nominal sequential images with 2-h intervals are used to understand the dynamics of the Venusian atmosphere by estimating the wind vectors at the cloud top altitude, as well as the mass transportation of UV absorbers. The UVI is equipped with off-axial catadioptric optics, two bandpass filters, a diffuser installed in a filter wheel moving with a step motor, and a high sensitivity charge-coupled device with UV coating. The UVI images have spatial resolutions ranging from 200 m to 86 km at sub-spacecraft points. The UVI has been kept in good condition during the extended interplanetary cruise by carefully designed operations that have maintained its temperature maintenance and avoided solar radiation damage. The images have signal-to-noise ratios of over 100 after onboard desmear processing.