Granulovirus PK-1 kinase activity relies on a side-to-side dimerization mode centered on the regulatory αC helix

The life cycle of Baculoviridae family insect viruses depends on the viral protein kinase, PK-1, to phosphorylate the regulatory protein, p6.9, to induce baculoviral genome release. Here, we report the crystal structure of Cydia pomenella granulovirus PK-1, which, owing to its likely ancestral origin among host cell AGC kinases, exhibits a eukaryotic protein kinase fold. PK-1 occurs as a rigid dimer, where an antiparallel arrangement of the αC helices at the dimer core stabilizes PK-1 in a closed, active conformation. Dimerization is facilitated by C-lobe:C-lobe and N-lobe:N-lobe interactions between protomers, including the domain-swapping of an N-terminal helix that crowns a contiguous β-sheet formed by the two N-lobes. PK-1 retains a dimeric conformation in solution, which is crucial for catalytic activity. Our studies raise the prospect that parallel, side-to-side dimeric arrangements that lock kinase domains in a catalytically-active conformation could function more broadly as a regulatory mechanism among eukaryotic protein kinases

Scintillation-limited photometry with the 20-cm NGTS telescopes at Paranal Observatory

Ground-based photometry of bright stars is expected to be limited by atmospheric scintillation, although in practice observations are often limited by other sources of systematic noise. We analyse 122 nights of bright star (Gmag ≲ 11.5) photometry using the 20-cm telescopes of the Next-Generation Transit Survey (NGTS) at the Paranal Observatory in Chile. We compare the noise properties to theoretical noise models and we demonstrate that NGTS photometry of bright stars is indeed limited by atmospheric scintillation. We determine a median scintillation coefficient at the Paranal Observatory of CY=1.54⁠, which is in good agreement with previous results derived from turbulence profiling measurements at the observatory. We find that separate NGTS telescopes make consistent measurements of scintillation when simultaneously monitoring the same field. Using contemporaneous meteorological data, we find that higher wind speeds at the tropopause correlate with a decrease in long-exposure (t = 10 s) scintillation. Hence, the winter months between June and August provide the best conditions for high-precision photometry of bright stars at the Paranal Observatory. This work demonstrates that NGTS photometric data, collected for searching for exoplanets, contains within it a record of the scintillation conditions at Paranal

Hypertrophic Cardiomyopathy with Left Ventricular Systolic Dysfunction: Insights from the SHaRe Registry

Background: The term "end stage" has been used to describe hypertrophic cardiomyopathy (HCM) with left ventricular systolic dysfunction (LVSD), defined as occurring when left ventricular ejection fraction is <50%. The prognosis of HCM-LVSD has reportedly been poor, but because of its relative rarity, the natural history remains incompletely characterized. Methods: Data from 11 high-volume HCM specialty centers making up the international SHaRe Registry (Sarcomeric Human Cardiomyopathy Registry) were used to describe the natural history of patients with HCM-LVSD. Cox proportional hazards models were used to identify predictors of prognosis and incident development. Results: From a cohort of 6793 patients with HCM, 553 (8%) met the criteria for HCM-LVSD. Overall, 75% of patients with HCM-LVSD experienced clinically relevant events, and 35% met the composite outcome (all-cause death [n=128], cardiac transplantation [n=55], or left ventricular assist device implantation [n=9]). After recognition of HCM-LVSD, the median time to composite outcome was 8.4 years. However, there was substantial individual variation in natural history. Significant predictors of the composite outcome included the presence of multiple pathogenic/likely pathogenic sarcomeric variants (hazard ratio [HR], 5.6 [95% CI, 2.3-13.5]), atrial fibrillation (HR, 2.6 [95% CI, 1.7-3.5]), and left ventricular ejection fraction <35% (HR, 2.0 [95% CI, 1.3-2.8]). The incidence of new HCM-LVSD was ≈7.5% over 15 years. Significant predictors of developing incident HCM-LVSD included greater left ventricular cavity size (HR, 1.1 [95% CI, 1.0-1.3] and wall thickness (HR, 1.3 [95% CI, 1.1-1.4]), left ventricular ejection fraction of 50% to 60% (HR, 1.8 [95% CI, 1.2, 2.8]-2.8 [95% CI, 1.8-4.2]) at baseline evaluation, the presence of late gadolinium enhancement on cardiac magnetic resonance imaging (HR, 2.3 [95% CI, 1.0-4.9]), and the presence of a pathogenic/likely pathogenic sarcomeric variant, particularly in thin filament genes (HR, 1.5 [95% CI, 1.0-2.1] and 2.5 [95% CI, 1.2-5.1], respectively). Conclusions: HCM-LVSD affects ≈8% of patients with HCM. Although the natural history of HCM-LVSD was variable, 75% of patients experienced adverse events, including 35% experiencing a death equivalent an estimated median time of 8.4 years after developing systolic dysfunction. In addition to clinical features, genetic substrate appears to play a role in both prognosis (multiple sarcomeric variants) and the risk for incident development of HCM-LVSD (thin filament variants)

Different paths to the modern state in Europe: the interaction between domestic political economy and interstate competition

Theoretical work on state formation and capacity has focused mostly on early modern Europe and on the experience of western European states during this period. While a number of European states monopolized domestic tax collection and achieved gains in state capacity during the early modern era, for others revenues stagnated or even declined, and these variations motivated alternative hypotheses for determinants of fiscal and state capacity. In this study we test the basic hypotheses in the existing literature making use of the large date set we have compiled for all of the leading states across the continent. We find strong empirical support for two prevailing threads in the literature, arguing respectively that interstate wars and changes in economic structure towards an urbanized economy had positive fiscal impact. Regarding the main point of contention in the theoretical literature, whether it was representative or authoritarian political regimes that facilitated the gains in fiscal capacity, we do not find conclusive evidence that one performed better than the other. Instead, the empirical evidence we have gathered lends supports to the hypothesis that when under pressure of war, the fiscal performance of representative regimes was better in the more urbanized-commercial economies and the fiscal performance of authoritarian regimes was better in rural-agrarian economie

NGTS-28Ab:a short period transiting brown dwarf

We report the discovery of a brown dwarf orbiting a M1 host star. We first identified the brown dwarf within the Next Generation Transit Survey data, with supporting observations found in TESS sectors 11 and 38. We confirmed the discovery with follow-up photometry from the South African Astronomical Observatory, SPECULOOS-S, and TRAPPIST-S, and radial velocity measurements from HARPS, which allowed us to characterize the system. We find an orbital period of ∼1.25 d, a mass of 69.0+5.3-4.8 MJ, close to the hydrogen burning limit, and a radius of 0.95 ± 0.05 RJ. We determine the age to be &gt;0.5 Gyr, using model isochrones, which is found to be in agreement with spectral energy distribution fitting within errors. NGTS-28Ab is one of the shortest period systems found within the brown dwarf desert, as well as one of the highest mass brown dwarfs that transits an M dwarf. This makes NGTS-28Ab another important discovery within this scarcely populated region.</div

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

NGTS-21b: An Inflated Super-Jupiter Orbiting a Metal-poor K dwarf

We report the discovery of NGTS-21b, a massive hot Jupiter orbiting a low-mass star as part of the Next Generation Transit Survey (NGTS). The planet has a mass and radius of $2.36 \pm 0.21$ M$_{\rm J}$, and $1.33 \pm 0.03$ R$_{\rm J}$, and an orbital period of 1.543 days. The host is a K3V ($T_{\rm eff}=4660 \pm 41$, K) metal-poor (${\rm [Fe/H]}=-0.26 \pm 0.07$, dex) dwarf star with a mass and radius of $0.72 \pm 0.04$, M$_{\odot}$,and $0.86 \pm 0.04$, R$_{\odot}$. Its age and rotation period of $10.02^{+3.29}_{-7.30}$, Gyr and $17.88 \pm 0.08$, d respectively, are in accordance with the observed moderately low stellar activity level. When comparing NGTS-21b with currently known transiting hot Jupiters with similar equilibrium temperatures, it is found to have one of the largest measured radii despite its large mass. Inflation-free planetary structure models suggest the planet's atmosphere is inflated by $\sim21\%$, while inflationary models predict a radius consistent with observations, thus pointing to stellar irradiation as the probable origin of NGTS-21b's radius inflation. Additionally, NGTS-21b's bulk density ($1.25 \pm 0.15$, g/cm$^3$) is also amongst the largest within the population of metal-poor giant hosts ([Fe/H] < 0.0), helping to reveal a falling upper boundary in metallicity-planet density parameter space that is in concordance with core accretion formation models. The discovery of rare planetary systems such as NGTS-21 greatly contributes towards better constraints being placed on the formation and evolution mechanisms of massive planets orbiting low-mass stars.Comment: 12 pages, 13 figures, accepted for publication in MNRA