Protein O-glycosylation is a nutrient signaling mechanism that plays an essential role in maintaining cellular homeostasis across different species. In plants, SPINDLY (SPY) and SECRET AGENT (SEC) posttranslationally modify hundreds of intracellular proteins with O-fucose and O-linked N-acetylglucosamine, respectively. SPY and SEC play overlapping roles in cellular regulation, and loss of both SPY and SEC causes embryo lethality in Arabidopsis (Arabidopsis thaliana). Using structure-based virtual screening of chemical libraries followed by in vitro and in planta assays, we identified a SPY O-fucosyltransferase inhibitor (SOFTI). Computational analyses predicted that SOFTI binds to the GDP-fucose-binding pocket of SPY and competitively inhibits GDP-fucose binding. In vitro assays confirmed that SOFTI interacts with SPY and inhibits its O-fucosyltransferase activity. Docking analysis identified additional SOFTI analogs that showed stronger inhibitory activities. SOFTI treatment of Arabidopsis seedlings decreased protein O-fucosylation and elicited phenotypes similar to the spy mutants, including early seed germination, increased root hair density, and defective sugar-dependent growth. In contrast, SOFTI did not visibly affect the spy mutant. Similarly, SOFTI inhibited the sugar-dependent growth of tomato (Solanum lycopersicum) seedlings. These results demonstrate that SOFTI is a specific SPY O-fucosyltransferase inhibitor that can be used as a chemical tool for functional studies of O-fucosylation and potentially for agricultural management.

Copper shows limited isotopic variation in equilibrated mantle-derived silicate rocks, but large isotopic fractionation during kinetic processes. For example, lunar and terrestrial samples that have experienced evaporation were found to have an isotopic fractionation of up to 12.5%o in their Cu-65/Cu-63 ratios, while komatiites, lherzolites, mid-ocean ridge and ocean island basalts show negligible Cu isotope fractionation as a result of equilibrium partial melting and crystal fractionation. The contrast between the observed magnitudes of equilibrium and kinetic isotope fractionation for Cu calls for a better understanding of kinetic Cu isotope fractionation. One of the mechanisms for creating large kinetic isotopic fractionation even at magmatic temperatures is diffusion. In this study, we performed Cu isotopic measurements on Cu diffusion couple experiments to constrain the beta factor for Cu isotopic fractionation by diffusion. We demonstrate a Monte Carlo approach for the regression and error estimation of the measured isotope profiles, which yielded beta values of 0.16 +/- 0.03 and 0.18 +/- 0.03 for the two experimental charges measured. Our results are subsequently applied to a quantitative model for the evaporation of a molten sphere to discuss the role of diffusion in affecting the bulk Cu isotopic fractionation between liquid and vapor during evaporation. We apply the model to Cu evaporation experiments and tektite data to show that convection primarily governs mass transport for evaporation during tektite formation. In addition, we show that Cu isotopes can be used as a tool to test the role of kinetics during various magmatic processes such as magmatic sulfide ore deposit formation, porphyry-type ore deposit formation, and fluid-rock interactions.

We report a Fourier transform infrared analysis of functional groups in insoluble organic matter (IOM) extracted from a series of 100-500 mu m Ryugu grains collected during the two touchdowns of February 22 and July 11, 2019. IOM extracted from most of the samples is very similar to IOM in primitive CI, CM, and CR chondrites, and shows that the extent of thermal metamorphism in Ryugu regolith was, at best, very limited. One sample displays chemical signatures consistent with a very mild heating, likely due to asteroidal collision impacts. We also report a lower carbonyl abundance in Ryugu IOM samples compared to primitive chondrites, which could reflect the accretion of a less oxygenated precursor by Ryugu. The possible effects of hydrothermal alteration and terrestrial weathering are also discussed. Last, no firm conclusions could be drawn on the origin of the soluble outlier phases, observed along with IOM in this study and in the preliminary analysis of Ryugu samples. However, it is clear that the HF/HCl residues presented in this publication are a mix between IOM and the nitrogen-rich outlier phase.

Peripheral neurons terminate at the surface of tendons partly to relay nociceptive pain signals; however, the role of peripheral nerves in tendon injury and repair remains unclear. Here, we show that after Achilles tendon injury in mice, there is new nerve growth near tendon cells that express nerve growth factor (NGF). Conditional deletion of the Ngf gene in either myeloid or mesenchymal mouse cells limited both innervation and tendon repair. Similarly, inhibition of the NGF receptor tropomyosin receptor kinase A (TrkA) abrogated tendon healing in mouse tendon injury. Sural nerve transection blocked the postinjury increase in tendon sensory innervation and the expansion of tendon sheath progenitor cells (TSPCs) expressing tubulin polymerization promoting protein family member 3. Single cell and spatial transcriptomics revealed that disruption of sensory innervation resulted in dysregulated inflammatory signaling and transforming growth factor-beta (TGFbeta) signaling in injured mouse tendon. Culture of mouse TSPCs with conditioned medium from dorsal root ganglia neuron further supported a role for neuronal mediators and TGFbeta signaling in TSPC proliferation. Transcriptomic and histologic analyses of injured human tendon biopsy samples supported a role for innervation and TGFbeta signaling in human tendon regeneration. Last, treating mice after tendon injury systemically with a small-molecule partial agonist of TrkA increased neurovascular response, TGFbeta signaling, TSPC expansion, and tendon tissue repair. Although further studies should investigate the potential effects of denervation on mechanical loading of tendon, our results suggest that peripheral innervation is critical for the regenerative response after acute tendon injury.

Alka(e)nes are produced by many living organisms and exhibit diverse physiological roles, reflecting a high functional versatility. Alka(e)nes serve as water proof wax in plants, communicating pheromones for insects, and microbial signaling molecules in some bacteria. Although alka(e)nes have been found in cyanobacteria and algal chloroplasts, a possible role in photosynthesis and chloroplast function remains elusive. In this study, we investigated the consequences of the absence of alka(e)nes on membrane lipid remodeling and photosynthesis using the cyanobacteria Synechocystis PCC6803 as a model organism. By following the dynamics of membrane lipids and the photosynthetic performance in strains defected and altered in alka(e)ne biosynthesis, we show that a profound remodeling of the membrane lipidome and carotenoid content occur in the absence of alka(e)nes, including a decrease in the membrane carotenoid content, a decrease in some digalactosyldiacylglycerol (DGDG) species and a parallel increase in monogalactosyldiacylglycerol (MGDG) species. Under high light, this effect is accompanied in alka(e)ne deficient strains by a higher susceptibility of photosynthesis and growth, the effect being reversed by expressing an algal photoenzyme producing alka(e)nes from fatty acids. We conclude that alka(e)nes play a crucial role in maintaining lipid homeostasis of photosynthetic membranes, thereby contributing to the proper functioning of photosynthesis, particularly under elevated light intensities.

The geometries of near-resonant planetary systems offer a relatively pristine window into the initial conditions of exoplanet systems. Given that near-resonant systems have likely experienced minimal dynamical disruptions, the spin-orbit orientations of these systems inform the typical outcomes of quiescent planet formation, as well as the primordial stellar obliquity distribution. However, few measurements have been made to constrain the spin-orbit orientations of near-resonant systems. We present a Rossiter-McLaughlin measurement of the near-resonant warm Jupiter TOI-2202 b, obtained using the Carnegie Planet Finder Spectrograph on the 6.5 m Magellan Clay Telescope. This is the eighth result from the Stellar Obliquities in Long-period Exoplanet Systems survey. We derive a sky-projected 2D spin-orbit angle lambda = 26(-15)(+12 degrees) and a 3D spin-orbit angle Psi = 31(-11)(+13 degrees), finding that TOI-2202 b-the most massive near-resonant exoplanet with a 3D spin-orbit constraint to date-likely deviates from exact alignment with the host star's equator. Incorporating the full census of spin-orbit measurements for near-resonant systems, we demonstrate that the current set of near-resonant systems with period ratios P-2/P-1 less than or similar to 4 is generally consistent with a quiescent formation pathway, with some room for low-level (less than or similar to 20 degrees) protoplanetary disk misalignments or post-disk-dispersal spin-orbit excitation. Our result constitutes the first population-wide analysis of spin-orbit geometries for near-resonant planetary systems.

Analyses of pulsar timing data have provided evidence for a stochastic gravitational wave background in the nanohertz frequency band. The most plausible source of this background is the superposition of signals from millions of supermassive black hole binaries. The standard statistical techniques used to search for this background and assess its significance make several simplifying assumptions, namely (i) Gaussianity, (ii) isotropy, and most often, (iii) a power-law spectrum. However, a stochastic background from a finite collection of binaries does not exactly satisfy any of these assumptions. To understand the effect of these assumptions, we test standard analysis techniques on a large collection of realistic simulated data sets. The data-set length, observing schedule, and noise levels were chosen to emulate the NANOGrav 15 yr data set. Simulated signals from millions of binaries drawn from models based on the Illustris cosmological hydrodynamical simulation were added to the data. We find that the standard statistical methods perform remarkably well on these simulated data sets, even though their fundamental assumptions are not strictly met. They are able to achieve a confident detection of the background. However, even for a fixed set of astrophysical parameters, different realizations of the universe result in a large variance in the significance and recovered parameters of the background. We also find that the presence of loud individual binaries can bias the spectral recovery of the background if we do not account for them.

Stripped-envelope supernovae (SESNe) are a subclass of core-collapse supernovae that are deficient in hydrogen (SN IIb, SN Ib) and possibly helium (SN Ic) in their spectra. Their progenitors are likely stripped of this material through a combination of stellar winds and interactions with a close binary companion, but the exact ejecta mass range covered by each subtype and how it relates to the zero-age main-sequence progenitor mass is still unclear. Using a combination of semianalytic modeling and numerical simulations, we discuss how the properties of SESN progenitors can be constrained through different phases of the bolometric light curve. We find that the light-curve rise time is strongly impacted by the strength of radioactive nickel mixing and treatment of helium recombination. These can vary between events and are often not accounted for in simpler modeling approaches, leading to large uncertainties in ejecta masses inferred from the rise. Motivated by this, we focus on the late-time slope, which is determined by gamma-ray leakage. We calibrate the relationship between ejecta mass, explosion energy, and gamma-ray escape time T 0 using a suite of numerical models. Application of the fitting function we provide to bolometric light curves of SESNe should result in ejecta masses with approximately 20% uncertainty. With large samples of SESNe coming from current and upcoming surveys, our methods can be utilized to better understand the diversity and origin of the progenitor stars.

The positions and velocities of stellar streams have been used to constrain the mass and shape of the Milky Way's dark matter halo. Several extragalactic streams have already been detected, though it has remained unclear what can be inferred about the gravitational potential from only 2D photometric data of a stream. We present a fast method to infer halo shapes from the curvature of 2D projected stream tracks. We show that the stream curvature vector must point within 90 degrees of the projected acceleration vector, in the absence of recent time-dependent perturbations. While insensitive to the total magnitude of the acceleration, and therefore the total mass, applying this constraint along a stream can determine halo shape parameters and place limits on disk-to-halo mass ratios. The most informative streams are those with sharp turns or flat segments, since these streams sample a wide range of curvature vectors over a small area (sharp turns) or have a vanishing projected acceleration component (flat segments). We apply our method to low surface brightness imaging of NGC 5907, and find that its dark matter halo is oblate. Our analytic approach is significantly faster than other stream modeling techniques, and indicates which parts of a stream contribute to constraints on the potential. The method enables a measurement of dark matter halo shapes for thousands of systems using stellar stream detections expected from upcoming facilities like Rubin and Roman.

Context. The final stages of molecular cloud evolution involve cloud disruption due to feedback by massive stars, with recent literature suggesting the importance of early (i.e., pre-supernova) feedback mechanisms.