Transits of Known Planets Orbiting a Naked-Eye Star

© 2020 The American Astronomical Society. All rights reserved.Some of the most scientifically valuable transiting planets are those that were already known from radial velocity (RV) surveys. This is primarily because their orbits are well characterized and they preferentially orbit bright stars that are the targets of RV surveys. The Transiting Exoplanet Survey Satellite (TESS) provides an opportunity to survey most of the known exoplanet systems in a systematic fashion to detect possible transits of their planets. HD 136352 (Nu2 Lupi) is a naked-eye (V = 5.78) G-type main-sequence star that was discovered to host three planets with orbital periods of 11.6, 27.6, and 108.1 days via RV monitoring with the High Accuracy Radial velocity Planet Searcher (HARPS) spectrograph. We present the detection and characterization of transits for the two inner planets of the HD 136352 system, revealing radii of 1.482-0.056+0.058 R ⊕ and 2.608-0.077+0.078 R ⊕ for planets b and c, respectively. We combine new HARPS observations with RV data from the Keck/High Resolution Echelle Spectrometer and the Anglo-Australian Telescope, along with TESS photometry from Sector 12, to perform a complete analysis of the system parameters. The combined data analysis results in extracted bulk density values of ρb = 7.8-1.1+1.2 g cm-3 and ρc = 3.50-0.36+0.41 g cm-3 for planets b and c, respectively, thus placing them on either side of the radius valley. The combination of the multitransiting planet system, the bright host star, and the diversity of planetary interiors and atmospheres means this will likely become a cornerstone system for atmospheric and orbital characterization of small worlds.Peer reviewe

Kynurenine–3–monooxygenase inhibition prevents multiple organ failure in rodent models of acute pancreatitis

Acute pancreatitis (AP) is a common and devastating inflammatory condition of the pancreas that is considered to be a paradigm of sterile inflammation leading to systemic multiple organ dysfunction syndrome (MODS) and death1,2 Acute mortality from AP-MODS exceeds 20%3 and for those who survive the initial episode, their lifespan is typically shorter than the general population4. There are no specific therapies available that protect individuals against AP-MODS. Here, we show that kynurenine-3-monooxygenase (KMO), a key enzyme of tryptophan metabolism5, is central to the pathogenesis of AP-MODS. We created a mouse strain deficient for Kmo with a robust biochemical phenotype that protected against extrapancreatic tissue injury to lung, kidney and liver in experimental AP-MODS. A medicinal chemistry strategy based on modifications of the kynurenine substrate led to the discovery of GSK180 as a potent and specific inhibitor of KMO. The binding mode of the inhibitor in the active site was confirmed by X-ray co-crystallography at 3.2 Å resolution. Treatment with GSK180 resulted in rapid changes in levels of kynurenine pathway metabolites in vivo and afforded therapeutic protection against AP-MODS in a rat model of AP. Our findings establish KMO inhibition as a novel therapeutic strategy in the treatment of AP-MODS and open up a new area for drug discovery in critical illness

Mitochondrial and microsomal ferric b\u3csub\u3e5\u3c/sub\u3e cytochromes exhibit divergent conformational plasticity in the context of a common fold

Native-state hydrogen-deuterium exchange (HDX) monitored by NMR spectroscopy has been used to compare conformational plasticity in ferric rat liver outer mitochondrial membrane cytochrome b5 (rOM b5) and ferric bovine liver microsomal cytochrome b5 (bMc b5). Analysis of the data indicated that rOM b5 is the less conformationally flexible protein on the time scale probed by the HDX experiments. The data also suggest a likely contributor to the much higher kinetic barrier for the release of hemin from OM b5S in comparison to Mc b5s, a characteristic that may be to a large extent the source of their divergent functional properties. Specifically, the data indicate that conformational mobility within helices α4 and α5, which flank the loop harboring axial ligand His63, is considerably more restricted in rOM b 5 than in bMc b5. The lower conformational flexibility of α4 and α5 in rOM b5 can reasonably be attributed to more extensive hydrophobic packing in that region of the protein, arising from two conserved side chain packing motifs in OM cytochrome b5s [Altuve, A., Wang, L., Benson, D. R., and Rivera, M. (2004) Biochem. Biophys. Res. Commun. 314, 602-609]. © 2005 American Chemical Society

Oxidation of Heme to β- and δ-Biliverdin by Pseudomonas a

The origin of the unusual regioselectivity of heme oxygenation, i.e. the oxidation of heme to δ-biliverdin (70%) and β-biliverdin (30%), that is exhibited by heme oxygenase from Pseudomonas aeruginosa (pa-HO) has been studied by 1H NMR, 13C NMR, and resonance Raman spectroscopies. Whereas resonance Raman indicates that the heme-iron ligation in pa-HO is homologous to that observed in previously studied α-hydroxylating heme oxygenases, the NMR spectroscopic studies suggest that the heme in this enzyme is seated in a manner that is distinct from that observed for all other α-hydroxylating heme oxygenase enzymes for which a structure is known. In pa-HO, the heme is rotated in-plane ∼ 110°, so the δ-meso-carbon of the major orientational isomer is located within the HO-fold in the place where the α-hydroxylating enzymes typically place the α-meso-carbon. The unusual heme seating displayed by pa- HO places the heme propionates so that these groups point in the direction of the solvent-exposed heme edge and appears to originate in large part from the absence of stabilizing interactions between the polypeptide and the heme propionates, which are typically found in α-hydroxylating heme oxygenase enzymes. These interactions typically involve Lys-16 and Tyr-112, in Neisseriae meningitidis HO, and Lys-16 and Tyr-134, in human and rat HO-1. The corresponding residues in pa-HO are Asn-19 and Phe-117, respectively. In agreement with this hypothesis, we found that the Asn-19 Lys/Phe-117 Tyr double mutant of pa-HO exists as a mixture of molecules exhibiting two distinct heme seatings; one seating is identical to that exhibited by wild-type pa-HO, whereas the alternative seating is very similar to that typical of α-hydroxylating heme oxygenase enzymes and is related to the wild-type seating by ∼ 110° in-plane rotation of the heme. Furthermore, each of these heme seatings in the pa-HO double mutant gives rise to a subset of two heme isomeric orientations that are related to each other by 180° rotation about the α-γ-mesoaxis. The coexistence of these molecules in solution, in the proportions suggested by the corresponding area under the peaks in the 1H NMR spectrum, explains the unusual regioselectivity of heme oxygenation observed with the double mutant, which we found produces α- (55%), δ- (35%), and β-biliverdin (10%). α-Biliverdin is obtained by oxidation of the heme seated similar to that of α-hydroxylating enzymes, whereas β- and δ-biliverdin are formed from the oxidation of heme seated as in wild-type pa-HO

The epidemiology of glioma in adults: a “state of the science” review

Gliomas are the most common primary intracranial tumor, representing 81% of malignant brain tumors. Although relatively rare, they cause significant mortality and morbidity. Glioblastoma, the most common glioma histology (∼45% of all gliomas), has a 5-year relative survival of ∼5%. A small portion of these tumors are caused by Mendelian disorders, including neurofibromatosis, tuberous sclerosis, and Li-Fraumeni syndrome. Genomic analyses of glioma have also produced new evidence about risk and prognosis. Recently discovered biomarkers that indicate improved survival include O⁶-methylguanine-DNA methyltransferase methylation, isocitrate dehydrogenase mutation, and a glioma cytosine-phosphate-guanine island methylator phenotype. Genome-wide association studies have identified heritable risk alleles within 7 genes that are associated with increased risk of glioma. Many risk factors have been examined as potential contributors to glioma risk. Most significantly, these include an increase in risk by exposure to ionizing radiation and a decrease in risk by history of allergies or atopic disease(s). The potential influence of occupational exposures and cellular phones has also been examined, with inconclusive results. We provide a “state of the science” review of current research into causes and risk factors for gliomas in adults