The structure and catalytic mechanism of a poly(ADP-ribose) glycohydrolase

Post-translational modification of proteins by poly(ADP-ribosyl)ation regulates many cellular pathways that are critical for genome stability, including DNA repair, chromatin structure, mitosis and apoptosis1. Poly(ADP-ribose) (PAR) is composed of repeating ADP-ribose units linked via a unique glycosidic ribose–ribose bond, and is synthesized from NAD by PAR polymerases1, 2. PAR glycohydrolase (PARG) is the only protein capable of specific hydrolysis of the ribose–ribose bonds present in PAR chains; its deficiency leads to cell death3, 4. Here we show that filamentous fungi and a number of bacteria possess a divergent form of PARG that has all the main characteristics of the human PARG enzyme. We present the first PARG crystal structure (derived from the bacterium Thermomonospora curvata), which reveals that the PARG catalytic domain is a distant member of the ubiquitous ADP-ribose-binding macrodomain family5, 6. High-resolution structures of T. curvata PARG in complexes with ADP-ribose and the PARG inhibitor ADP-HPD, complemented by biochemical studies, allow us to propose a model for PAR binding and catalysis by PARG. The insights into the PARG structure and catalytic mechanism should greatly improve our understanding of how PARG activity controls reversible protein poly(ADP-ribosyl)ation and potentially of how the defects in this regulation are linked to human disease

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Thermochemistry of adducts of some bivalent transition metal bromides with pyridine

The compounds [MBr2(py)(2)] (where M is Mn(II), Co(II), Ni(II), Cu(II) or Zn(II); py = pyridine) were synthesized and characterized by melting points, elemental analysis, thermal analysis and electronic and IR spectroscopy. The enthalpies of dissolution of the adducts, metal(II) bromides and pyridine in 25% (v/v) 1.2 M aqueous HCl in methanol were measured and by using thermochemical cycles, the following thermochemical ;parameters for the adducts have been determined: the standard enthalpies for the Lewis acid/base reactions (Delta H-r(theta)), the standard enthalpies of formation (Delta H-r(theta)), the standard enthalpics of decomposition (Delta H-D(theta)), the lattice standard enthalpies (Delta H-M(theta)) and the standard enthalpies of the Lewis acid/base reactions in the gaseous phase (Delta H-r(theta)(g)). The mean bond dissociation enthalpies of the M(II)-nitrogen bonds have been estimated as well as the enthalpies of the adducts formation in the gaseous phase. (c) 2007 Elsevier B.V. All rights reserved.4561323

Thermochemistry of aniline derivatives complexes of arsenic trihalides

The complexes AsX(3) . nL (where L is 2,6-dimethylaniline(dimean), o-, m- or p-chloroaniline (o-, m- or p-chloran), n = 1, 3/2, 5/2 or 3, and X is Cl, Br or I) were synthesized and characterized by melting points, elemental analysis, TG and DTG analysis, mass spectra and IR spectroscopy. From the enthalpies of dissolution in 25% (v/v) ethanolic ethanolamine and using appropriate thermochemical cycles, the following thermochemical parameters for the adducts have been determined: the standard enthalpies for the Lewis acid/base reaction (Delta(r)H(circle minus)), the standard enthalpies of formation (Delta(f)H(circle minus)), the standard enthalpies of decomposition (Delta(D)H(circle minus)), the lattice standard enthalpies (Delta(M)H(circle minus)), and the enthalpies of the Lewis acid/base reactions in the gaseous phase (Delta(r)H(circle minus)(g)). The mean standard enthalpies of the arsenic-nitrogen bonds have been estimated.268839

Thermochemistry of aniline-derivative adducts of nickel(II) acetylacetonate

The compounds [Ni(acac)(2)(L)(2)] (where acac is acetylacetonate and L is aniline (an), 2,6-dimethylaniline (dimean), o- or m-chloroaniline (o- or m-clan)) were synthesized and characterized by melting points, elemental analysis, TG-DTG, and DSC curves and electronic and IR spectroscopy. The enthalpies of dissolution of the adducts, Ni(II) acetylacetonate and ligands in a 1 : 3 (v/v) mixture of aqueous HCl 1.2 M and methanol, were measured and by using thermochemical cycles the following thermochemical parameters for the adducts have been determined: The standard enthalpies for the Lewis acid/base reaction (Delta(r)H(theta)), the standard enthalpies of formation (Delta(f)H(theta)), the standard enthalpies of decomposition (Delta(D)H(theta)), the lattice standard enthalpies (Delta(M)H(theta)) and the standard enthalpies of the Lewis acid/base reactions ire the gaseous phase (Delta(r)H(theta)(g)). The mean standard enthalpies of the nickel-nitrogen bonds have been estimated. (C) 1999 Elsevier Science B.V. All rights reserved.333151

THERMOCHEMISTRY OF BENZENAMINE ADDUCTS OF ARSENIC TRIHALIDES

The adducts AsX3.3L [where L = benzenamine (An), 2-nitrobenzenamine (o-NO2An), 3-nitrobenzenamine (m-NO2An), or 4-nitrobenzenamine (p-NO2An) and X = Cl, Br, or I] were synthesized and characterized by melting points, elemental analysis, thermal studies, and infrared spectroscopy. From calorimetric studies in solution, the mean standard enthalpies of the arsenic-nitrogen bond were determined.39466766

Thermochemistry of adducts of tin(IV) bromide with amide and thioamide ligands

The compounds SnBr4. nL (where L is urea (u), 1,1-dimethylurea (1,1-dmu). 1,3-dimethylurea (1,3-dmu), tetramethylurea (tmu), thiourea (tu), tetramethylthiourea (tmu) or 1-allyl-2-thiourea (atu) and n = 2, 3 or 4) were synthesized and characterized by melting points, elemental analysis, thermal analysis and IR spectroscopy. The enthalpies of dissolution of the adducts, tin(IV) bromide and ligands in methanol were measured and by using thermochemical cycles the following thermochemical parameters for the adducts have been determined: the standard enthalpies for the Lewis acid/base reaction (Delta H-r(0)); the standard enthalpies of formation (Delta H-f(0)) the standard enthalpies of decomposition (Delta H-D(0)); the lattice standard enthalpies (Delta H-M(0)) and the standard enthalpies of the Lewis acid/base reaction in the gaseous phase (Delta H-r(0)(g)). The mean standard enthalpies of the tin-oxygen ((D) over bar ((Sn-O))) and tin-sulphur ((D) over bar ((Sn-S))) bonds have been estimated. (C) 2001 Elsevier Science B.V. All rights reserved.3694167191

Thermochemistry of adducts of tin(IV) bromide with heterocyclic bases

The compounds [SnBr4(L)(n)] (where L is pyridine (py), 3-methylpyridine (beta-pico), 4-methylpyridine (gamma-pico), piperidine (pipd), morpholine (morph), piperazine (pipz), 3-cyanopyridine (3-cyanopy), 4-cyanopyridine (4-cyanopy), quinoline (quin) or 2.2'-bipyridine (bipy) and n = 1 or 2) were synthesized and characterized by elemental analysis, melting points, thermal studies and IR spectroscopy. The enthalpies of dissolution of adducts, tin(IV) bromide and ligands in 25% (v/v) aqueous 1.2 M HCl in methanol were measured and, by thermochemical cycles, the standard enthalpies for the Lewis acid/base reaction (Delta(r)H(theta)), the standard enthalpies of formation (Delta(f)H(theta)), the standard enthalpies of decomposition (Delta(D)H(theta)), the lattice standard enthalpies (Delta(M)H(theta)) and the standard enthalpies for the Lewis acid/base reaction in the gaseous phase (Delta(r)H(theta)(g)) are determined. The mean standard enthalpies of the tin-nitrogen coordinated bonds D(Sn-N) are estimated. (C) 2003 Elsevier Science B.V. All rights reserved.4044167111712

Thermochemistry of adducts of some bivalent transition metal bromides with quinoline

The compounds [MBr2(quin)(n)] (where M is Mn(II), Co(II), Ni(II), Cu(II) or Zn(II); quin, quinoline; n = 1 or 2) were synthesized and characterized by melting points, elemental analysis, thermal analysis and electronic and IR spectroscopy. The enthalpies of dissolution of the adducts, metal(II) bromides and quinoline in methanol or 1.2 M aqueous HCl were measured and by using thermochemical cycles, the following parameters for the adducts have been determined: the standard enthalpies for the Lewis acid/base reactions (Delta H-r degrees), the standard enthalpies of formation (Delta H-f degrees), the standard enthalpies of decomposition (Delta H-D degrees), the lattice standard enthalpies (Delta H-M degrees) and the standard enthalpies of the Lewis acid/base reactions in the gaseous phase (Delta H-r degrees(g)). The mean bond dissociation enthalpies of the M(II)-nitrogen bonds ((D) over bar ((M-N))) have been estimated as well as the enthalpies of adduct formation in the gaseous phase. (c) 2007 Elsevier B.V. All rights reserved.46841671212

Thermochemistry of adducts of tin(IV) bromide with ligands containing amide or thioamide groups

The compounds [SnBr4(L)2] (where L is formamide (fa), acetamide (a), N,N-dimethylacetamide (dma), benzamide (ba), thioacetamide (ta), N,N-dimethylthioformamide (dmtf), NN-dimethylthioacetamide (dmta) or thiobenzamide (tba)) were synthesized and characterized by melting points, elemental analysis, thermal analysis and IR spectroscopy. The enthalpies of dissolution of the adducts, tin(IV) bromide and ligands in methanol were measured and by using thermochemical cycles the following thermochemical parameters for the adducts have been deter-mined: the standard enthalpies for the Lewis acid/base reactions (Delta(r)H(theta)), the standard enthalpies of formation (Delta(f)H(0)), the standard enthalpies of decomposition (Delta(D)H(0)), the lattice standard enthalpies (Delta(M)H(0)) and the standard enthalpies of the Lewis acid/base reactions in the gaseous phase (DeltarH(theta)(g). The mean bond dissociation enthalpies of the tin(IV)-oxygen ((D) over bar ((Sn-S))) and tin(IV)-sulphur bonds (D) over bar((Sn-O))) have been estimated. (C) 2002 Elsevier Science B.V. All rights reserved.38941671253