bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systems Toxicology
Authors: Talikka Marja , Boué Stephanie , Frentzel Stefan , Kogel Ulrike , Sierro Nicolas , Titz Bjorn , Veljkovic Emilija , Hoeng Julia , Peitsch Manuel C. 
Published: June 2016

AbstractThe human respiratory tract is exposed to numerous contaminants; traditional toxicity testing methods are insufficient to understand the extent of their biological impact and to recommend dose guidelines for safe exposure. Systems toxicology approaches are starting to shape the way for a better assessment of toxicity associated with inhaled substances. A well‐designed assessment pipeline begins with the choice of the experimental system, exposure modality, and characterization of the exposure. The different omics technologies are a crucial part of modern toxicity testing by providing a holistic, unbiased view of a substance's impact. Transcriptomics technologies give insight into the differential expression of genes resulting from exposures, and genomics technologies assess the impact on the DNA itself. Large‐scale proteomics and metabolomics measurements provide additional layers of data and enable the detailed interpretation of the outcome of differential gene expression and the analysis of processes. Network biology is emerging as a powerful tool to filter relevant signal from noise using a priori knowledge. The quantitative aspect of network scoring allows the comparison of different doses and exposure durations and represents the impact as a single holistic score. Crowd sourcing facilitates the collaborative and transparent establishment and verification of toxicity testing methods.
ArylamineN‐Acetyltransferases
Authors: Grant Denis M. 
Published: June 2016

AbstractArylamineN‐acetyltransferases (NATs) are phase II xenobiotic‐conjugating enzymes that have a restricted substrate preference for theN‐ orO‐acetylation of aromatic amine and theirN‐oxidized metabolites. Although the number of clinically useful drugs whose disposition depends on acetylation is relatively small, the risk for toxicity from these agents is significant. In addition, a much larger number of potentially hazardous environmental aromatic amines may be acetylated, and this process may contribute to either the detoxication or the metabolic activation of such chemicals into reactive electrophiles with the potential to damage cellular macromolecules. The structures of the two human NAT enzymes NAT1 and NAT2 have been determined; the structural features allow for the detailed description of a two‐step catalytic mechanism and for a rationalization of their distinct substrate preferences. Although the human isoniazid acetylation polymorphism is controlled by allelic variation at theNAT2gene locus, a considerable variation exists in theNAT1gene. Numerous associations have been reported between variable NAT function and risk for cancers associated with exposure to aromatic amines. In addition, possible novel roles for NAT1 and its mammalian orthologs in folate homeostasis and in cellular proliferation are being actively explored.
Aluminum: Organometallic Chemistry
Authors: Mason Mark R. 
Published: June 2016

AbstractThe synthesis, reactivity, structures, and applications of the organometallic compounds of aluminum are reviewed. This article starts with a discussion of traditional synthetic approaches to aluminum alkyls, aryls, hydrides, and halides and continues with a discussion of their structures and reactivity. The following section focuses on the emerging organometallic chemistry of Al(0), Al(I), and Al(II) and specifically highlights recent developments in aluminum–aluminum bonding, insertions of small molecules and elements into Al–Al bonds, and the isolation of large metalloid clusters such as . Organoaluminum heterocycles and cage compounds are the subjects of the next section that briefly describes the common structural motifs and has separate subsections devoted to cage iminoalanes, alkylaluminoxanes, alkylaluminophosphinates, ‐phosphates, ‐phosphonates, and ‐arsonates. Structural relationships among these groups of compounds and comparisons to secondary building units in aluminophosphate molecular sieves are presented. The importance of alkylaluminoxanes to catalytic activity is also discussed. This article includes an independent section on cationic organoaluminum complexes. Although this includes more traditional cationic complexes ligated by crown ether and neutral nitrogen‐donor ligands, the section emphasizes the recent developments in generating two‐ and three‐coordinate cationic complexes. Alkide and hydride abstractions by trityl salts of weakly coordinating anions and tris(pentafluorophenyl)borane are described. Common anion decomposition pathways and successful cationic systems for oligomerizing and polymerizing alkenes are discussed. Two additional sections describe the applications of organoaluminum compounds to organic synthesis and applications in industry. Readers are referred to leading works that more adequately describe the extensive use of organoaluminum reagents in organic synthesis. Current and past applications of organoaluminum compounds for the production of long‐chain alkenes and alcohols, as cocatalysts for Ziegler–Natta and metallocene‐catalyzed polymerization of alkenes and dienes and catalysts for alkene oligomerization and epoxide polymerization, are summarized. Safety issues regarding the handling and disposal of pyrophoric organoaluminum reagents and waste are also discussed. One hundred thirty seven reviews and original works are cited.
Biomineralization
Authors: Dauphin Yannicke 
Published: June 2016

AbstractBiominerals are a common feature in nature: they are bones and teeth, and also “shells”. They have been known for hundreds of millions of years in animals and plants. Three main categories exist: silica (sponges), calcium phosphates (bone, teeth), and calcium carbonates (shells). Calcium phosphates and calcium carbonates are mainly crystalline, whereas silica is not. Biominerals are a mixture of extracellular organic components and mineral, secreted by specialized cells and tissues. Their arrangement (micro‐ and nanostructure) and composition are species specific. Consequently, they clearly differ from their inorganically formed counterparts. The organic components are proteins, polysaccharides, and lipids. Biominerals are used as diagnostic criteria for phylogeny, paleoenvironmental recorders in archeology and geology, medical uses, aquaculture, and biomimetics.
Gallium and Indium Compounds in Homogeneous Catalysis
Authors: Dagorne Samuel , Fliedel Christophe , de Frémont Pierre 
Published: June 2016

AbstractThe present contribution highlights the most recent and representative developments on the use of Ga and In species in homogeneous catalysis. Recent studies of various ligand‐supported Ga(III) and In(III) compounds in cyclic esters polymerization catalysis for the production of biodegradable polyester materials are also included. Various organic transformations may now be catalyzed using Ga(III) and In(III) Lewis acids allowing access to a wide range of valuable organic molecules through diverse reaction sequences. The recent use of stable and robustN‐heterocyclic carbene Ga(III) and In(III) compounds as strong π‐Lewis acid catalysts for various organic reactions is also discussed: such species are certainly promising for the future developments of Ga(III)‐ and In(III)‐mediated reactions. Although Lewis acid‐assisted reactions certainly dominate the field in Ga(III) and In(III) chemistry, discrete low‐valent In(I) species, presently emerging in catalysis, clearly display a distinct reactivity allowing their exploitation both as soft Lewis acids and alkyl‐/allyl‐/arylating agents.
Extracytoplasmic Nickel‐Binding Proteins
Authors: Cavazza Christine 
Published: June 2016

AbstractIn bacteria, nickel is required for the activation of at least nine enzymes. Among several nickel import systems dedicated to Ni(II) acquisition, canonical ABC‐type importers possess an extracytoplasmic nickel‐binding protein (or Ni‐BP) that serves as the initial receptor and the major determinant of the transporter specificity. Ni‐BPs evolved from peptide‐BPs from at least four independent evolutionary origins. Their evolutionary history is dominated by horizontal gene transfers among bacteria and Archaea, among Gram‐positive and Gram‐negative bacteria, and among organisms having different lifestyles. Phylogeny of Ni‐BPs explains the promiscuous behavior of this class of Ni(II) carriers. In the Ni‐BPs family, a diversity of nickel‐binding motifs was identified, precluding the determination of a common consensus nickel‐binding mode. Different strategies to bind Ni(II) in the protein cavity have been described. Ni‐BPs binds either free nickel ions or chelated Ni(II). Naked nickel binds to the protein via three histidine residues. In several Ni‐BPs, only one histidine residue is involved in direct nickel–protein contact and a chelator that binds to the protein via supramolecular interactions is required to complete the coordination sphere of the metal. InStaphylococcus aureus, Ni‐BPs do not possess any histidine in their nickel‐binding motifs and the nickel complex is stabilized in the binding pockets via salt bridges with arginines and interactions with aromatic residues. Depending on the growth conditions and nickel availability in the environment, the chelators are either available molecules in the environment such as L‐histidine or by‐products of the metabolism or putative endogenous biosynthetic nickelophores.
BacillussubtilisPhosphodiesterasePhoD
Authors: Rodriguez Fernanda , Lillington James 
Published: June 2016

AbstractBacillus subtilisPhoD is an extracytoplasmic alkaline phosphodiesterase that liberates phosphate from organic compounds. PhoD active site contains one Fe3+ion and two Ca2+ions. Structurally, PhoD is similar to the metallophosphatase family of eukaryotic purple acid phosphatases (PAPs). PAPs have two metal ions at their active site, Fe3+and M2+of variable identity. M2+is frequently an Fe or Zn. As in the PAPs, the Fe3+ion in PhoD is coordinated to a tyrosine. However, PhoD has a Ca2+at the M2+site, and a second supporting Ca2+. PhoD also exhibits a C‐terminal α‐helix, which buries the active site. It is probable that the C‐terminal α‐helix has a regulatory role in PhoD activity.
The Ectoine Hydroxylase: A Nonheme‐Containing Iron(
II
) and 2‐Oxoglutarate‐Dependent Dioxygenase
Authors: Widderich Nils , Bremer Erhard , Smits Sander HJ 
Published: June 2016

Abstract
Ectoine and 5‐hydroxyectoine are well‐recognized members of the compatible solutes and are widely employed by microorganisms as osmostress protectants. The EctABC enzymes catalyze the synthesis of ectoine. A subgroup of the ectoine producers can convert ectoine into 5‐hydroxyectoine through a region‐selective and stereospecific hydroxylation reaction catalyzed by the EctD protein, a member of the nonheme‐containing iron(II) and 2‐oxoglutarate‐dependent dioxygenase superfamily.

Structures of EctD are known from the
Virgibacillus salexigens
EctD protein in its apo‐ and iron‐bound forms. Furthermore, a set of crystal structures is known from the EctD protein from
Sphingopyxis alaskensis
in its apo‐ and Fe(II)‐bound forms and also from a dead‐end complex of EctD together with the substrate 2‐oxogluterate and the product 5‐hydroxyectoine. In this article, we describe the purification and biochemically characterization of nine different EctD proteins from different species. Furthermore, the importance of the Fe(II) ligand and its binding site is described. The octahedral geometry of Fe(II) binding is mediated
via
two histidine and one aspartate side chain together with water molecules. The latter are replaced by the binding of the 2‐oxoglutarate substrate to the EctD enzyme. The binding mechanism of Fe(II) is strictly conserved within the EctD protein superfamily.
Bacterial Siderophore‐Binding ProteinFepB
Authors: Krewulak Karla D , Vogel Hans J 
Published: June 2016

AbstractMany bacteria can produce and secrete ferric‐iron‐specific chelators, called siderophores, to remove bound ferric iron from host proteins. The catecholate‐type siderophore enterobactin is a high‐affinity siderophore that is used by many Gram‐negative and Gram‐positive bacteria to acquire iron. In Gram‐negative bacteria, the ferric‐enterobactin (Fep) uptake system includes the outer membrane receptor FepA, the periplasmic binding protein (PBP) FepB, and the cytoplasmic membrane ABC transporter FepDG and FepC. FepB is a PBP with a type III structure fold, which has two independently folded domains linked together by a long α‐helix. This article will provide a comprehensive look at the structural and functional aspects of the 34 kDa PBP FepB.
Fe‐S‐Basedl‐Serine Dehydratases
Authors: Holden Hazel M , Thoden James B , Grant Gregory A 
Published: June 2016

Abstractl‐Serine dehydratases are nonredox iron‐sulfur proteins that convertl‐serine to pyruvate and ammonia. They are found only in bacteria and contain a diamagnetic [4Fe‐4S]2+center that acts as a Lewis acid. In addition to a catalytic domain that contains the Fe‐S cluster, they also possess at least one other structural domain that may be involved in the regulation of catalytic activity. At least four types are known that are differentiated based on their domain arrangements and number of polypeptide chains. The available crystal structure is that fromLegionella pneumophila, which shows a bilobal molecule with the active site at the interface of two domains. In this structure, a C‐terminal cysteine residue forms a fourth coordination site with the Fe‐S cluster that appears to act as an intrinsic competitive inhibitor as it interacts with the cluster in a manner very similar to that which would be required by the substrate. Kinetic evidence supports a model wherel‐serine binds to a second noncatalytic site to activate the enzyme and induce the opening of the active site to substrate.
Anisotropic3DColloidal Quantum Nanostructures
Authors: Govan Joseph , Spiridonov Igor , Fedorov Anatoly , Baranov Alexander , Gun'ko Yurii K. 
Published: June 2016

Abstract3D anisotropic semiconductor nanostructures have unique physical properties including a high aspect ratio, optical polarization anisotropy, polarized photoluminescence, giant birefringence, and many others. Theoretical studies of anisotropic semiconductor nanostructures have shown that their electronic and optical properties dramatically depend on their shape and size. These factors open up an access to new generation of optical, optoelectronic, and light‐harvesting devices. In this article, we demonstrate advances in the development of new 3D quantum‐confined colloidal nanostructures such as semiconductor nanotetrapods, nanomultipods, nanoflowers, nanostar and other shapes. We present the latest progress in various colloidal chemistry approaches for the synthesis of these nanostructures. We also consider the self‐organization of quantum dots in 3D superparticles. We discuss structure–property relations as well as the corresponding potential applications of these nanomaterials in light‐harvesting, energy‐conversion devices, sensing, photocatalysis, biology, and other areas. Finally, we provide conclusions and an outlook for the future development of anisotropic semiconductor nanomaterials and their technological prospects.
Ring‐Opening/Expansion Rearrangement of Cycloprop[2,3]inden‐1‐ols Catalyzed by p‐Toluenesulfonic Acid
Authors: Li Pei‐Fang , Yi Cheng‐Bo , Ren Shu‐Jian , Qu Jin 
Published: June 2016

AbstractA divergent approach to generate either 1‐hydroxymethylindenes (which could then be converted to benzofulvenes through a dehydration reaction) or naphthalenes by the rearrangement of cycloprop[2,3]inden‐1‐ols is reported. The effect of the cyclopropyl ring substitution pattern on ring‐opening/expansion rearrangements of the substrates was systemically studied.magnified image
Recent Advances in Highly Selective Applications of Nitroso Compounds
Authors: Huang Jiapian , Chen Zhiyuan , Yuan Jianjun , Peng Yiyuan 
Published: June 2016

AbstractOver the past few years, substantial progress has been achieved in nitroso‐related organic chemistry. Annulation reactions of nitroso compounds with other π‐conjugated systems, in particular through the notable hetero‐Diels–Alder‐type reaction, have drawn much interest from organic chemists because of their high regioselectivities, enantioselectivities, and efficiencies. In addition, the N‐nitroso moiety can also be employed as a powerful and transformable directing group in direct C−H functionalization reactions. Herein, we summarize recent reports on the versatile applications of nitroso compounds as useful building blocks in the selective synthesis of a diverse range of molecules.
Totalsynthese von Aurantosid G, einer N‐β‐glycosylierten 3‐Oligoenoyltetramsäure aus Theonella swinhoei
Authors: Petermichl Markus , Loscher Sebastian , Schobert Rainer 
Published: June 2016

AbstractErstmals wurde eine natürliche N‐glycosylierte 3‐Acyltetramsäure synthetisiert. Aurantosid G ist ein tiefroter, in Reinsubstanz höchst empfindlicher Metabolit des Meeresschwammes Theonella swinhoei. Es hat eine chlorsubstituierte Dodecapentaenoyl‐Seitenkette an einer l‐Asparagin‐abgeleiteten Tetramsäure, deren Lactam‐Stickstoffatom eine β‐konfigurierte d‐Xylose trägt. Die Seitenkette wurde über konsekutive Wittig‐ und HWE‐Olefinierungen aufgebaut und für die N‐Acylierung eines Asparaginats verwendet, dessen Aminogruppe bereits vorher über eine Fukuyama‐Mitsunobu‐Reaktion mit einer d‐Xylose verknüpft worden war. In diesem N‐Acylierungsschritt wurde auch die für die fungizide Aktivität essenzielle β‐Konfiguration der Xylose festgelegt, wofür große, elektronenreiche PMB‐Schutzgruppen am Zucker verantwortlich sind. Der Heterocyclus wurde zuletzt quantitativ durch eine basische Lacey‐Dieckmann‐Kondensation eines vollständig entschützten N‐(β‐Ketoacyl)aminosäuresters geschlossen.
Highly Stereoselective Cobalt(III)‐Catalyzed Three‐Component C−H Bond Addition Cascade
Authors: Boerth Jeffrey A. , Hummel Joshua R. , Ellman Jonathan A. 
Published: June 2016

AbstractA highly stereoselective three‐component C(sp2)−H bond addition across alkene and polarized π‐bonds is reported for which CoIII catalysis was shown to be much more effective than RhIII. The reaction proceeds at ambient temperature with both aryl and alkyl enones employed as efficient coupling partners. Moreover, the reaction exhibits extremely broad scope with respect to the aldehyde input; electron rich and poor aromatic, alkenyl, and branched and unbranched alkyl aldehydes all couple in good yield and with high diastereoselectivity. Multiple directing groups participate in this transformation, including pyrazole, pyridine, and imine functional groups. Both aromatic and alkenyl C(sp2)−H bonds undergo the three‐component addition cascade, and the alkenyl addition product can readily be converted into diastereomerically pure five‐membered lactones. Additionally, the first asymmetric reactions with CoIII‐catalyzed C−H functionalization are demonstrated with three‐component C−H bond addition cascades employing N‐tert‐butanesulfinyl imines. These examples represent the first transition metal catalyzed C−H bond additions to N‐tert‐butanesulfinyl imines, which are versatile and extensively used intermediates for the asymmetric synthesis of amines.
Total Synthesis of Aurantoside G, an N‐β‐Glycosylated 3‐Oligoenoyltetramic Acid from Theonella swinhoei
Authors: Petermichl Markus , Loscher Sebastian , Schobert Rainer 
Published: June 2016

AbstractThe first synthesis of a natural N‐glycosylated 3‐acyltetramic acid is reported. Aurantoside G (1 g), a deep‐red metabolite of the marine sponge Theonella swinhoei, is highly delicate in the pure state. It features a chlorinated dodecapentaenoyl side chain at an l‐asparagine‐derived tetramic acid, the ring nitrogen atom of which is linked to a β‐configured d‐xylose. The side chain was built through consecutive Wittig and HWE reactions and used to N‐acylate the amino group of an asparaginate that had already been N‐xylosylated through a Fukuyama–Mitsunobu reaction. This N‐acylation step fixes the β‐configuration of the xylose, which is essential for the antifungal activity, but only if the sugar carries bulky, electron‐rich protecting groups such as PMB. In the final step, the heterocycle was closed quantitatively through a basic Lacey–Dieckmann condensation of an entirely unprotected precursor.
A Cinchona Alkaloid‐Functionalized Mesostructured Silica for Construction of Enriched Chiral β‐Trifluoromethyl‐β‐Hydroxy Ketones over An Epoxidation‐Relay Reduction Process
Authors: Li Cuibao , Shu Xiaomin , Li Liang , Zhang Genwei , Jin Ronghua , Cheng Tanyu , Liu Guohua 
Published: June 2016

AbstractA cinchona alkaloid‐functionalized heterogeneous catalyst is prepared through a thiol‐ene click reaction of chiral N‐(3,5‐ditrifluoromethylbenzyl)quininium bromide and a mesostructured silica, which is obtained by co‐condensation of 1,2‐bis(triethoxysilyl)ethane and 3‐(triethoxysilyl)propane‐1‐thiol. Structural analyses and characterizations disclose its well‐defined chiral single‐site active center, and electron microscopy images reveal its monodisperse property. As a heterogenous catalyst, it enables an efficient asymmetric epoxidation of achiral β‐trifluoromethyl‐β,β‐disubstituted enones, the obtained chiral products can then be converted easily into enriched chiral β‐trifluoromethyl‐β‐hydroxy ketones through a sequential epoxidation‐relay reduction process. Furthermore, such a heterogeneous catalyst can be recovered conveniently and reused in asymmetric epoxidation of 4,4,4‐trifluoro‐1,3‐diphenylbut‐2‐enone, showing an attractive feature in a practical construction of enriched chiral β‐CF3‐substituted molecules.
Use of azathioprine and corticosteroids during pregnancy and birth outcome in women diagnosed with inflammatory bowel disease
Authors: Plauborg Anne Veie , Hansen Anne Vinkel , Garne Ester 
Published: June 2016

BackgroundThe aim of this study was to describe prescription patterns for azathioprine and corticosteroids for pregnant women with inflammatory bowel diseases (IBD) before, during, and after pregnancy and to describe pregnancy outcomes.MethodsA cohort composed of all singleton pregnancies in Danish registries from 1996 to 2009 was divided by maternal IBD status: Crohn's disease (CD, n = 827), ulcerative colitis (UC, N = 1361), or no IBD diagnosis (background population, n = 814,231). The number of women with a prescription for azathioprine, local and systemic steroids within a 3‐month period was computed for each of the pregnancy trimesters and the year before and after pregnancy. Outcomes of interest were stillbirth, perinatal mortality, low birth weight (LBW), preterm birth, and small for gestational age (SGA).ResultsNumber of prescriptions for azathioprine decreased just before and during pregnancy and increased after birth. Number of prescriptions for local and systemic corticosteroids decreased approximately 30% compared with before pregnancy and increased in the second trimester. There was an increased risk among mothers with IBD of LBW (adjusted odds ratio [adjOR]: CD: 2.25 [95% confidence interval {CI}, 1.74–2.91], UC: 1.81 [95% CI, 1.42–2.30]), preterm birth (adjOR: CD: 2.54 [95% CI, 2.04–3.15], UC: 1.86 [95% CI, 1.52–2.27]), and SGA (adjOR: CD: 1.99 [95% CI, 1.26–3.15], UC: 1.80 [95% CI, 1.18–2.75]).ConclusionUse of azathioprine and corticosteroids was often reduced or discontinued before or during early pregnancy followed by an increased use of corticosteroids later in pregnancy. Women diagnosed with IBD and with prescriptions for azathioprine and/or corticosteroids, have an increased risk of LBW, pre‐term birth, and SGA. Birth Defects Research (Part A) 106:494–499, 2016. © 2016 Wiley Periodicals, Inc.