Identification of Pseudomonas aeruginosa Phenazines that Kill Caenorhabditis elegans

Pathogenic microbes employ a variety of methods to overcome host defenses, including the production and dispersal of molecules that are toxic to their hosts. Pseudomonas aeruginosa, a Gram-negative bacterium, is a pathogen of a diverse variety of hosts including mammals and the nematode Caenorhabditis elegans. In this study, we identify three small molecules in the phenazine class that are produced by P. aeruginosa strain PA14 that are toxic to C. elegans. We demonstrate that 1-hydroxyphenazine, phenazine-1-carboxylic acid, and pyocyanin are capable of killing nematodes in a matter of hours. 1-hydroxyphenazine is toxic over a wide pH range, whereas the toxicities of phenazine-1-carboxylic acid and pyocyanin are pH-dependent at non-overlapping pH ranges. We found that acidification of the growth medium by PA14 activates the toxicity of phenazine-1-carboxylic acid, which is the primary toxic agent towards C. elegans in our assay. Pyocyanin is not toxic under acidic conditions and 1-hydroxyphenazine is produced at concentrations too low to kill C. elegans. These results suggest a role for phenazine-1-carboxylic acid in mammalian pathogenesis because PA14 mutants deficient in phenazine production have been shown to be defective in pathogenesis in mice. More generally, these data demonstrate how diversity within a class of metabolites could affect bacterial toxicity in different environmental niches.Chemistry and Chemical Biolog

Atmospheric Characterization via Broadband Color Filters on the PLAnetary Transits and Oscillations of stars (PLATO) Mission

We assess broadband color filters for the two fast cameras on the PLAnetary Transits and Oscillations (PLATO) of stars space mission with respect to exoplanetary atmospheric characterization. We focus on Ultra Hot Jupiters and Hot Jupiters placed 25pc and 100pc away from the Earth and low mass low density planets placed 10pc and 25pc away. Our analysis takes as input literature values for the difference in transit depth between the broadband lower (500 to 675nm) wavelength interval (hereafter referred to as blue) and the upper (675-1125nm) broadband wavelength interval (hereafter referred to as red) for transmission, occultation and phase curve analyses. Planets orbiting main sequence central stars with stellar classes F, G, K and M are investigated. We calculate the signal-to-noise ratio with respect to photon and instrument noise for detecting the difference in transit depth between the two spectral intervals. Results suggest that bulk atmospheric composition and planetary geometric albedos could be detected for (Ultra) Hot Jupiters up to about 100pc (about 25pc) with strong (moderate) Rayleigh extinction. Phase curve information could be extracted for Ultra Hot Jupiters orbiting K and G dwarf stars up to 25pc away. For low mass low density planets, basic atmospheric types (primary and water-dominated) and the presence of sub-micron hazes in the upper atmosphere could be distinguished for up to a handful of cases up to about 10pc.Comment: accepted in Experimental Astronomy April 202

Direct and indirect mortality impacts of the COVID-19 pandemic in the United States, March 1, 2020 to January 1, 2022

Excess mortality studies provide crucial information regarding the health burden of pandemics and other large-scale events. Here, we used time series approaches to separate the direct contribution of SARS-CoV-2 infections on mortality from the indirect consequences of pandemic interventions and behavior changes in the United States. We estimated deaths occurring in excess of seasonal baselines stratified by state, age, week and cause (all causes, COVID-19 and respiratory diseases, Alzheimer’s disease, cancer, cerebrovascular disease, diabetes, heart disease, and external causes, including suicides, opioids, accidents) from March 1, 2020 to April 30, 2021. Our estimates of COVID-19 excess deaths were highly correlated with SARS-CoV-2 serology, lending support to our approach. Over the study period, we estimate an excess of 666,000 (95% Confidence Interval (CI) 556000, 774000) all-cause deaths, of which 90% could be attributed to the direct impact of SARS-CoV-2 infection, and 78% were reflected in official COVID-19 statistics. Mortality from all disease conditions rose during the pandemic, except for cancer. The largest direct impacts of the pandemic were seen in mortality from diabetes, Alzheimer’s, and heart diseases, and in age groups over 65 years. In contrast, the largest indirect consequences of the pandemic were seen in deaths from external causes, which increased by 45,300 (95% CI 30,800, 59,500) and were statistically linked to the intensity of non-pharmaceutical interventions. Within this category, increases were most pronounced in mortality from accidents and injuries, drug overdoses, and assaults and homicides, while the rate of death from suicides remained stable. Younger age groups suffered the brunt of these indirect effects. Overall, on a national scale, the largest consequences of the COVID-19 pandemic are attributable to the direct impact of SARS-CoV-2 infections; yet, the secondary impacts dominate among younger age groups, in periods of stricter interventions, and in mortality from external causes. Further research on the drivers of indirect mortality is warranted to optimize interventions in future pandemics

Large Interferometer For Exoplanets (LIFE): V. Diagnostic potential of a mid-infrared space-interferometer for studying Earth analogs

An important future goal in exoplanetology is to detect and characterize potentially habitable planets. Using nulling interferometry, LIFE will allow us to constrain the radius and effective temperature of (terrestrial) exoplanets, as well as provide unique information about their atmospheric structure and composition. We explore the potential of LIFE in characterizing emission spectra of Earth at various stages of its evolution. We perform Bayesian retrievals on simulated spectra of 8 different scenarios, which correspond to cloud-free and cloudy spectra of four different epochs of the evolution of the Earth. Assuming a distance of 10 pc and a Sun-like host star, we simulate observations obtained with LIFE using its simulator LIFEsim, considering all major astrophysical noise sources. With the nominal spectral resolution (R=50) and signal-to-noise ratio (assumed to be S/N=10 at 11.2 $\mu$m), we can identify the main spectral features of all the analyzed scenarios (most notably CO$_2$, H$_2$O, O$_3$, CH$_4$). This allows us to distinguish between inhabited and lifeless scenarios. Results suggest that particularly O$_3$ and CH$_4$ yield an improved abundance estimate by doubling the S/N from 10 to 20. We conclude that the baseline requirements for R and S/N are sufficient for LIFE to detect O$_3$ and CH$_4$ in the atmosphere of an Earth-like planet with an abundance of O$_2$ of around 2% in volume mixing ratio. This information is relevant in terms of the LIFE mission planning. We also conclude that cloud-free retrievals of cloudy planets can be used to characterize the atmospheric composition of terrestrial habitable planets, but not the thermal structure of the atmosphere. From the inter-model comparison performed, we deduce that differences in the opacity tables (caused by e.g. a different line wing treatment) may be an important source of systematic errors.Comment: 18 pages (main text, incl. 11 figures) + appendix; submitted to A&A; comments are very welcome! Fifth paper of LIFE telescope series. First: arXiv:2101.07500v4, Second: arXiv:2203.00471, Third: arXiv:2112.02054, Sixth: arXiv:2201.0489

Exoplanet Biosignatures: Observational Prospects

Exoplanet hunting efforts have revealed the prevalence of exotic worlds with diverse properties, including Earth-sized bodies, which has fueled our endeavor to search for life beyond the Solar System. Accumulating experiences in astrophysical, chemical, and climatological characterization of uninhabitable planets are paving the way to characterization of potentially habitable planets. In this paper, we review our possibilities and limitations in characterizing temperate terrestrial planets with future observational capabilities through 2030s and beyond, as a basis of a broad range of discussions on how to advance "astrobiology" with exoplanets. We discuss the observability of not only the proposed biosignature candidates themselves, but also of more general planetary properties that provide circumstantial evidence, since the evaluation of any biosignature candidate relies on their context. Characterization of temperate Earth-size planets in the coming years will focus on those around nearby late-type stars. JWST and later 30 meter-class ground-based telescopes will empower their chemical investigations. Spectroscopic studies of potentially habitable planets around solar-type stars will likely require a designated spacecraft mission for direct imaging, leveraging technologies that are already being developed and tested as part of the WFIRST mission. Successful initial characterization of a few nearby targets will be an important touchstone toward a more detailed scrutiny and a larger survey that are envisioned beyond 2030. The broad outlook this paper presents may help develop new observational techniques to detect relevant features as well as frameworks to diagnose planets based on the observables.Comment: part of a series of 5 review manuscripts of the NExSS Exoplanet Biosgnatures Worksho

Fresh air in the 21st century?

Ozone is an air quality problem today for much of the world's population. Regions can exceed the ozone air quality standards (AQS) through a combination of local emissions, meteorology favoring pollution episodes, and the clean-air baseline levels of ozone upon which pollution builds. The IPCC 2001 assessment studied a range of global emission scenarios and found that all but one projects increases in global tropospheric ozone during the 21st century. By 2030, near-surface increases over much of the northern hemisphere are estimated to be about 5 ppb (+2 to +7 ppb over the range of scenarios). By 2100 the two more extreme scenarios project baseline ozone increases of >20 ppb, while the other four scenarios give changes of -4 to +10 ppb. Even modest increases in the background abundance of tropospheric ozone might defeat current AQS strategies. The larger increases, however, would gravely threaten both urban and rural air quality over most of the northern hemisphere

Life Beyond the Solar System: Remotely Detectable Biosignatures

For the first time in human history, we will soon be able to apply to the scientific method to the question "Are We Alone?" The rapid advance of exoplanet discovery, planetary systems science, and telescope technology will soon allow scientists to search for life beyond our Solar System through direct observation of extrasolar planets. This endeavor will occur alongside searches for habitable environments and signs of life within our Solar System. While these searches are thematically related and will inform each other, they will require separate observational techniques. The search for life on exoplanets holds potential through the great diversity of worlds to be explored beyond our Solar System. However, there are also unique challenges related to the relatively limited data this search will obtain on any individual world

Main flexible pavement and mix design methods in Europe and challenges for the development of an european method

Pavement and mix design represent one of the key components within the life cycle of a road infrastructure, with links to political, economic, technical, societal and environmental issues. Recent researches related to the characteristics of materials and associated behavior models both for materials and pavement, made it appropriate to consider updating current pavement design methods, and especially in the USA this has already been in process while in Europe uses of the methods developed in the early 1970s. Thus, this paper firstly presents a brief historical overview of pavement design methods, highlighting early limitations of old empirical methods. Afterwards, French, UK and Shell methods currently in use in Europe will be presented, underlining their main components in terms of methodology, traffic, climatic conditions and subgrade. The asphalt mix design and modeling in Europe are presented with their inclusion in the pavement design methods. Finally, the main challenges for the development of a European pavement design method are presented as well as the recent research developments that can be used for that methodThe second author would like to express the support of Portuguese National Funding Agency for Science, Research and Technology (FCT) through scholarship SFRH/BSAB/114415/ 2016. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.info:eu-repo/semantics/publishedVersio

Combined point of care nucleic acid and antibody testing for SARS-CoV-2 following emergence of D614G Spike Variant

Rapid COVID-19 diagnosis in hospital is essential, though complicated by 30-50% of nose/throat swabs being negative by SARS-CoV-2 nucleic acid amplification testing (NAAT). Furthermore, the D614G spike mutant now dominates the pandemic and it is unclear how serological tests designed to detect anti-Spike antibodies perform against this variant. We assess the diagnostic accuracy of combined rapid antibody point of care (POC) and nucleic acid assays for suspected COVID-19 disease due to either wild type or the D614G spike mutant SARS-CoV-2. The overall detection rate for COVID-19 is 79.2% (95CI 57.8-92.9%) by rapid NAAT alone. Combined point of care antibody test and rapid NAAT is not impacted by D614G and results in very high sensitivity for COVID-19 diagnosis with very high specificity

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era