We performed RNA-seq and high-resolution mass spectrometry on 128 blood samples from COVID-19-positive and COVID-19-negative patients with diverse disease severities and outcomes. Quantified transcripts, proteins, metabolites, and lipids were associated with clinical outcomes in a curated relational database, uniquely enabling systems analysis and cross-ome correlations to molecules and patient prognoses. We mapped 219 molecular features with high significance to COVID-19 status and severity, many of which were involved in complement activation, dysregulated lipid transport, and neutrophil activation. We identified sets of covarying molecules, e.g., protein gelsolin and metabolite citrate or plasmalogens and apolipoproteins, offering pathophysiological insights and therapeutic suggestions. The observed dysregulation of platelet function, blood coagulation, acute phase response, and endotheliopathy further illuminated the unique COVID-19 phenotype. We present a web-based tool (covid-omics.app) enabling interactive exploration of our compendium and illustrate its utility through a machine learning approach for prediction of COVID-19 severity.

The Michelson Interferometer for Global High-resolution imaging of the Thermosphere and Ionosphere (MIGHTI) instrument was built for launch and operation on the NASA Ionospheric Connection Explorer (ICON) mission. The instrument was designed to measure thermospheric horizontal wind velocity profiles and thermospheric temperature in altitude regions between 90km and 300km, during day and night. For the wind measurements it uses two perpendicular fields of view pointed at the Earth's limb, observing the Doppler shift of the atomic oxygen red and green lines at 630.0nm and 557.7nm wavelength. The wavelength shift is measured using field-widened, temperature compensated Doppler Asymmetric Spatial Heterodyne (DASH) spectrometers, employing low order échelle gratings operating at two different orders for the different atmospheric lines. The temperature measurement is accomplished by a multichannel photometric measurement of the spectral shape of the molecular oxygen A-band around 762nm wavelength. For each field of view, the signals of the two oxygen lines and the A-band are detected on different regions of a single, cooled, frame transfer charge coupled device (CCD) detector. On-board calibration sources are used to periodically quantify thermal drifts, simultaneously with observing the atmosphere. The MIGHTI requirements, the resulting instrument design and the calibration are described.

We systematically surveyed period variations of superhumps in SU UMa-type dwarf novae based on newly obtained data and past publications. In many systems, the evolution of the superhump period is found to be composed of three distinct stages: an early evolutionary stage with a longer superhump period, a middle stage with systematically varying periods, and a final stage with a shorter, stable superhump period. During the middle stage, many systems with superhump periods of less than 0.08 d show positive period derivatives. We present observational characteristics of these stages and give greatly improved statistics. Contrary to an earlier claim, we found no clear evidence for a variation of period derivatives among different superoutbursts of the same object. We present an interpretation that the lengthening of the superhump period is a result of the outward propagation of an eccentricity wave, which is limited by the radius near the tidal truncation. We interpret that late-stage superhumps are rejuvenated excitation of a 3:1 resonance when superhumps in the outer disk are effectively quenched. The general behavior of the period variation, particularly in systems with short orbital periods, appears to follow a scenario proposed in Kato, Maehara, and Monard (2008, PASJ, 60, L23). We also present an observational summary of WZ Sge-type dwarf novae. Many of them have shown long-enduring superhumps during a post-superoutburst stage having longer periods than those during the main superoutburst. The period derivatives in WZ Sge-type dwarf novae are found to be strongly correlated with the fractional superhump excess, or consequently with the mass ratio. WZ Sge-type dwarf novae with a long-lasting rebrightening or with multiple rebrightenings tend to have smaller period derivatives, and are excellent candidates for those systems around or after the period minimum of evolution of cataclysmic variables.

Ferroptosis, triggered by discoordination of iron, thiols and lipids, leads to accumulation of 15-hydroperoxy-arachidonoyl-PE (15-HpETE-PE) generated by complexes of 15-lipoxygenase (15-LOX) and a scaffold protein, PEBP1. As Ca 2+ -independent phospholipase PLA 2 (iPLA 2 β, PLA2G6/PNPLA9 gene), can preferentially hydrolyze peroxidized phospholipids, it may eliminate ferroptotic 15-HpETE-PE death signal. Here we demonstrate that by hydrolyzing 15-HpETE-PE, iPLA 2 β averts ferroptosis whereas its genetic or pharmacological inactivation sensitizes cells to ferroptosis. Given that PLA2G6/PNPLA9 mutations relate to neurodegeneration, we examined fibroblasts from a patient with a Parkinson’s disease (PD)-associated mutation fPD R747W and found selectively decreased 15-HpETE-PE hydrolyzing activity, 15-HpETE-PE accumulation and elevated sensitivity to ferroptosis. CRISPR-CAS9-engineered PNPLA9 R748W/R748W mice exhibited progressive parkinsonian motor deficits and 15-HpETE-PE accumulation. Elevated 15-HpETE-PE levels were also detected in midbrains of rotenone-infused parkinsonian rats and α-synuclein mutant SNCA-A53T mice with decreased iPLA 2 β expression and PD-relevant phenotype. Thus, iPLA 2 β is a new ferroptosis regulator and its mutations may be implicated in PD pathogenesis.

Microbial symbionts are often a source of chemical novelty and can contribute to host defense against antagonists. However, the ecological relevance of chemical mediators remains unclear for most systems. Lagria beetles live in symbiosis with multiple strains of Burkholderia bacteria that protect their offspring against pathogens. Here, we describe the antifungal polyketide lagriamide, and provide evidence supporting that it is produced by an uncultured symbiont, Burkholderia gladioli Lv-StB, which is dominant in field-collected Lagria villosa. Interestingly, lagriamide is structurally similar to bistramides, defensive compounds found in marine tunicates. We identify a gene cluster that is probably involved in lagriamide biosynthesis, provide evidence for horizontal acquisition of these genes, and show that the naturally occurring symbiont strains on the egg are protective in the soil environment. Our findings highlight the potential of microbial symbionts and horizontal gene transfer as influential sources of ecological innovation.

How black holes accrete surrounding matter is a fundamental yet unsolved question in astrophysics. It is generally believed that matter is absorbed into black holes via accretion disks, the state of which depends primarily on the mass-accretion rate. When this rate approaches the critical rate (the Eddington limit), thermal instability is supposed to occur in the inner disk, causing repetitive patterns of large-amplitude X-ray variability (oscillations) on timescales of minutes to hours. In fact, such oscillations have been observed only in sources with a high mass-accretion rate, such as GRS 1915+105 (refs 2, 3). These large-amplitude, relatively slow timescale, phenomena are thought to have physical origins distinct from those of X-ray or optical variations with small amplitudes and fast timescales (less than about 10 seconds) often observed in other black-hole binaries-for example, XTE J1118+480 (ref. 4) and GX 339-4 (ref. 5). Here we report an extensive multi-colour optical photometric data set of V404 Cygni, an X-ray transient source containing a black hole of nine solar masses (and a companion star) at a distance of 2.4 kiloparsecs (ref. 8). Our data show that optical oscillations on timescales of 100 seconds to 2.5 hours can occur at mass-accretion rates more than ten times lower than previously thought. This suggests that the accretion rate is not the critical parameter for inducing inner-disk instabilities. Instead, we propose that a long orbital period is a key condition for these large-amplitude oscillations, because the outer part of the large disk in binaries with long orbital periods will have surface densities too low to maintain sustained mass accretion to the inner part of the disk. The lack of sustained accretion--not the actual rate--would then be the critical factor causing large-amplitude oscillations in long-period systems.

We performed RNA-Seq and high-resolution mass spectrometry on 128 blood samples from COVID-19 positive and negative patients with diverse disease severities. Over 17,000 transcripts, proteins, metabolites, and lipids were quantified and associated with clinical outcomes in a curated relational database, uniquely enabling systems analysis and cross-ome correlations to molecules and patient prognoses. We mapped 219 molecular features with high significance to COVID-19 status and severity, many involved in complement activation, dysregulated lipid transport, and neutrophil activation. We identified sets of covarying molecules, e.g., protein gelsolin and metabolite citrate or plasmalogens and apolipoproteins, offering pathophysiological insights and therapeutic suggestions. The observed dysregulation of platelet function, blood coagulation, acute phase response, and endotheliopathy further illuminated the unique COVID-19 phenotype. We present a web-based tool (covid-omics.app) enabling interactive exploration of our compendium and illustrate its utility through a comparative analysis with published data and a machine learning approach for prediction of COVID-19 severity.

Secondary metabolites, which are small-molecule organic compounds produced by living organisms, provide or inspire drugs for many different diseases. These natural products have evolved over millions of years to provide a survival benefit to the producing organism and often display potent biological activity with important therapeutic applications. For instance, defensive compounds in the environment may be cytotoxic to eukaryotic cells, a property exploitable for cancer treatment. Here, we describe the genome of an uncultured symbiotic bacterium that makes such a cytotoxic metabolite. This symbiont is losing genes that do not endow a selective advantage in a hospitable host environment. Secondary metabolism genes, however, are repeated multiple times in the genome, directly demonstrating their selective advantage. This finding shows the strength of selective forces in symbiotic relationships and suggests that uncultured bacteria in such relationships should be targeted for drug discovery efforts.