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Orotate phosphoribosyltransferase (OPRT) catalyzes the reaction that adds the pyrimidine base to the ribose in the penultimate step of the de novo biosynthesis of pyrimidine nucleotides. The OPRT structure consists of an obligate dimer, conserved throughout the phosphoribosyltransferase family. Here, we describe the structural characterization of Burkholderia cenocepacia OPRT (BcOPRT), both by X-ray crystallography and Cryo electron microscopy (Cryo-EM). While the known dimer is present in the structure of BcOPRT, a putative hexameric form was also observed by multiple methods. Analyses by chromatography, Cryo-EM, and kinetics indicate that both dimeric and hexameric forms of this enzyme are present together in solution. Comparison of the kinetics of the native protein and two variants, which were specifically designed to prevent hexamerization, reveal that only the hexameric form is enzymatically active. Collectively, these data suggest that BcOPRT may use oligomerization to control overall enzymatic activity, thus contributing to the local regulation of pyrimidine biosynthesis in this organism. 

Burkholderia cenocepaciais an opportunistic human pathogen that can cause lethal infections in immunocompromised individuals, particularly those with cystic fibrosis. As such, there is a critical need to identify and characterize the structure and function of enzymes that participate in the metabolic pathways of this bacterium. Here, the high-resolution X-ray crystal structure of a short-chain dehydrogenase reductase (SDR) fromB. cenocepaciaJ2315 (BcSDR) in complex with the coenzyme NADP⁺and a benzoic acid ligand is presented. This protein has the conserved Rossmann fold of the SDR superfamily and the characteristic TGxxxGxG motif of the classical SDR subfamily. However, unlike classical SDRs, the active site of BcSDR has a leucine residue in place of the highly conserved and catalytically important tyrosine residue. Sequence analysis confirms that this leucine residue is conserved in this SDR across the Burkholderiales order. This suggests that BcSDR is more appropriately classified into the divergent SDR subfamily. In addition, this enzyme would necessarily employ a different enzyme mechanism to that proposed as a general mechanism for most SDRs. 

The Colorado Plateau has abundant oil, gas, and alternative energy potential. This energy potential is scattered among a patchwork of land ownership, with private, tribal, and public lands being actively developed for energy extraction. Elements of biodiversity (e.g., listed and sensitive plant and animal species) are distributed among all land tenures, yet the laws protecting them can vary as a function of land tenure. It is imperative to understand the spatial distributions of threatened endangered, and sensitive species in relation to land tenure to preserve habitat and conserve species populations in areas undergoing energy development. We developed species distribution models and spatial conservation optimization frameworks to explore the interactions among land ownership, existing and potential energy extraction, and biodiversity. Four management scenarios were tested to quantify how different approaches to energy extraction may impact rare plant distributions. Results show that incorporating risk and land tenure in spatially optimized frameworks it is possible to facilitate the long-term viability of rare plant species. The scenarios developed here represent a different attitude towards the value of rare plants and the risk of energy development. Results gives insight into the financial consequences of rare species protection and quantifies the biodiversity costs of energy development across landscapes. 

ABSTRACT We explore the assumption, widely used in many astrophysical calculations, that the stellar initial mass function (IMF) is universal across all galaxies. By considering both a canonical broken-power-law IMF and a non-universal IMF, we are able to compare the effect of different IMFs on multiple observables and derived quantities in astrophysics. Specifically, we consider a non-universal IMF that varies as a function of the local star formation rate, and explore the effects on the star formation rate density (SFRD), the extragalactic background light, the supernova (both core-collapse and thermonuclear) rates, and the diffuse supernova neutrino background. Our most interesting result is that our adopted varying IMF leads to much greater uncertainty on the SFRD at $$z \approx 2-4$$ than is usually assumed. Indeed, we find an SFRD (inferred using observed galaxy luminosity distributions) that is a factor of $$\gtrsim 3$$ lower than canonical results obtained using a universal IMF. Secondly, the non-universal IMF we explore implies a reduction in the supernova core-collapse rate of a factor of $$\sim 2$$, compared against a universal IMF. The other potential tracers are only slightly affected by changes to the properties of the IMF. We find that currently available data do not provide a clear preference for universal or non-universal IMF. However, improvements to measurements of the star formation rate and core-collapse supernova rate at redshifts $$z \gtrsim 2$$ may offer the best prospects for discernment. 

Paleo-detectors are a proposed experimental technique to search for dark matter (DM). In lieu of the conventional approach of operating a tonne-scale real-time detector to search for DM-induced nuclear recoils, paleo-detectors take advantage of small samples of naturally occurring rocks on Earth that have been deep underground (≳5 km), accumulating nuclear damage tracks from recoiling nuclei for O(1)Gyr. Modern microscopy techniques promise the capability to read out nuclear damage tracks with nanometer resolution in macroscopic samples. Thanks to their O(1)Gyr integration times, paleo-detectors could constitute nuclear recoil detectors with keV recoil energy thresholds and 100 kilotonne-yr exposures. This combination would allow paleo-detectors to probe DM-nucleon cross sections orders of magnitude below existing upper limits from conventional direct detection experiments. In this article, we use improved background modeling and a new spectral analysis technique to update the sensitivity forecast for paleo-detectors. We demonstrate the robustness of the sensitivity forecast to the (lack of) ancillary measurements of the age of the samples and the parameters controlling the backgrounds, systematic mismodeling of the spectral shape of the backgrounds, and the radiopurity of the mineral samples. Specifically, we demonstrate that even if the uranium concentration in paleo-detector samples is 10−8 (per weight), many orders of magnitude larger than what we expect in the most radiopure samples obtained from ultra basic rock or marine evaporite deposits, paleo-detectors could still probe DM-nucleon cross sections below current limits. For DM masses ≲ 10 GeV/c2, the sensitivity of paleo-detectors could still reach down all the way to the conventional neutrino floor in a Xe-based direct detection experiment. 

Abstract In recent years, there have been significant advances in multimessenger astronomy due to the discovery of the first, and so far only confirmed, gravitational wave event with a simultaneous electromagnetic (EM) counterpart, as well as improvements in numerical simulations, gravitational wave (GW) detectors, and transient astronomy. This has led to the exciting possibility of performing joint analyses of the GW and EM data, providing additional constraints on fundamental properties of the binary progenitor and merger remnant. Here, we present a new Bayesian framework that allows inference of these properties, while taking into account the systematic modeling uncertainties that arise when mapping from GW binary progenitor properties to photometric light curves. We extend the relative binning method presented in Zackay et al. to include extrinsic GW parameters for fast analysis of the GW signal. The focus of our EM framework is on light curves arising from r -process nucleosynthesis in the ejected material during and after merger, the so-called kilonova, and particularly on black hole−neutron star systems. As a case study, we examine the recent detection of GW190425, where the primary object is consistent with being either a black hole or a neutron star. We show quantitatively how improved mapping between binary progenitor and outflow properties, and/or an increase in EM data quantity and quality are required in order to break degeneracies in the fundamental source parameters.