bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysregulation of protein phosphatase 2A in parkinson disease and dementia with lewy bodies
Authors: Park Hye‐Jin , Lee Kang‐Woo , Park Eun S. , Oh Stephanie , Yan Run , Zhang Jie , Beach Thomas G. , Adler Charles H. , Voronkov Michael , Braithwaite Steven P. , Stock Jeffry B. , Mouradian M. Maral 
Published: September 2016

AbstractObjectiveProtein phosphatase 2A (PP2A) is a heterotrimeric holoenzyme composed of a catalytic C subunit, a structural A subunit, and one of several regulatory B subunits that confer substrate specificity. The assembly and activity of PP2A are regulated by reversible methylation of the C subunit. α‐Synuclein, which aggregates in Parkinson disease (PD) and dementia with Lewy bodies (DLB), is phosphorylated at Ser129, and PP2A containing a B55α subunit is a major phospho‐Ser129 phosphatase. The objective of this study was to investigate PP2A in α‐synucleinopathies.MethodsWe compared the state of PP2A methylation, as well as the expression of its methylating enzyme, leucine carboxyl methyltransferase (LCMT‐1), and demethylating enzyme, protein phosphatase methylesterase (PME‐1), in postmortem brains from PD and DLB cases as well as age‐matched Controls. Immunohistochemical studies and quantitative image analysis were employed.ResultsLCMT‐1 was significantly reduced in the substantia nigra (SN) and frontal cortex in both PD and DLB. PME‐1, on the other hand, was elevated in the PD SN. In concert with these changes, the ratio of methylated PP2A to demethylated PP2A was markedly decreased in PD and DLB brains in both SN and frontal cortex. No changes in total PP2A or total B55α subunit were detected.InterpretationThese findings support the hypothesis that PP2A dysregulation in α‐synucleinopathies may contribute to the accumulation of hyperphosphorylated α‐synuclein and to the disease process, raising the possibility that pharmacological means to enhance PP2A phosphatase activity may be a useful disease‐modifying therapeutic approach.
Insights into N‐Heterocyclic Carbene‐Catalyzed [4+2] Annulation Reaction of Enals with Nitroalkenes: Mechanisms, Origin of Chemo‐ and Stereoselectivity, and Role of Catalyst
Authors: Zheng Linjie , Wang Yang , Wei Donghui , Qiao Yan 
Published: September 2016

AbstractIn this paper, density functional theory (DFT) calculations have been employed to investigate the detailed mechanisms, origin of chemo‐ and stereoselectivity, and role of catalyst for the reaction of enals with nitroalkenes catalyzed by N‐heterocyclic carbenes (NHCs). The calculated results disclose that the reaction contains seven steps, that is, the nucleophilic attack on the α, β‐unsaturated aldehyde by NHC, the [1, 2]‐proton transfer for the formation of Breslow intermediate, the β‐protonation for affording enolate intermediate, the nucleophilic addition on the Re/Si face of enolate by the nitroalkenes, the [1, 5] proton transfer, the ring‐closure process, and the regeneration of NHC. The addition on the Re/Si face of enolate is identified to be the stereocontrolling step, in which the chiral centers including α‐carbon of enals and β‐carbon of nitroalkenes are formed. Moreover, the reaction pathway leading to the RR‐configured product has the lowest Gibbs free energy barrier, which is in agreement with the experimental observation. Furthermore, the analyses of electrophilic and nucleophilic Parr functions and global reactivity indices (GRIs) have been performed to explore the origin of chemoselectivity and the role of catalyst. This theoretical work would provide valuable insights for the rational design of more effective organocatalyst for this kind of reactions with high stereoselectivities.
Encapsulation of AGE‐Breaker Alagebrium by Cucurbit[7]uril Improved the Stability of Both Its Carbonyl α‐Hydrogen and Thiazolium C2‐Hydrogen
Authors: Li Shengke , Ding Yuan‐Fu , Yin Hang , Wang Chunming , Bardelang David , Wang Lian‐Hui , Wang Ruibing 
Published: September 2016

AbstractAs determined by both 1H NMR and UV/Vis spectroscopic titration, ESI‐MS, isothermal titration calorimetry, and DFT molecular modeling, advanced glycation end products (AGE) breaker alagebrium (ALA) formed 1:1 guest–host inclusion complexes with cucurbit[7]uril (CB[7]), with a binding affinity, Ka, in the order of magnitude of 105 m−1, thermodynamically driven by both enthalpy (ΔH=−6.79 kcal mol−1) and entropy (TΔS=1.21 kcal mol−1). For the first time, a dramatic inhibition of keto–enol tautomerism of the carbonyl α‐hydrogen of ALA has been observed, as evidenced by over an order of magnitude decrease of both the first step rate constant, k1, and the second step rate constant, k2, during hydrogen/deuterium exchange in D2O. Meanwhile, as expected, the reactivity of C2‐hydrogen was also inhibited significantly, with an upshift of 2.09 pKa units. This discovery will not only provide an emerging host molecule to modulate keto–enol tautomerism, but also potentially lead to a novel supramolecular formulation of AGE‐breaker ALA for improved stability and therapeutic efficacy.
Physiologically based pharmacokinetic–pharmacodynamic modeling to predict concentrations and actions of sodium‐dependent glucose transporter 2 inhibitor canagliflozin in human intestines and renal tubules
Authors: Mori Kazumi , Saito Ryuta , Nakamaru Yoshinobu , Shimizu Makiko , Yamazaki Hiroshi 
Published: September 2016

AbstractCanagliflozin is a recently developed sodium‐glucose cotransporter (SGLT) 2 inhibitor that promotes renal glucose excretion and is considered to inhibit renal SGLT2 from the luminal side of proximal tubules. Canagliflozin reportedly inhibits SGLT1 weakly and suppresses postprandial plasma glucose, suggesting that it also inhibits intestinal SGLT1. However, it is difficult to measure the drug concentrations of these assumed sites of action directly. The pharmacokinetic–pharmacodynamic (PK/PD) relationships of canagliflozin remain poorly characterized. Therefore, a physiologically based pharmacokinetic (PBPK) model of canagliflozin was developed based on clinical data from healthy volunteers and it was used to simulate luminal concentrations in intestines and renal tubules. In small intestine simulations, the inhibition ratios for SGLT1 were predicted to be 40%–60% after the oral administration of clinical doses (100–300 mg/day). In contrast, inhibition ratios of canagliflozin for renal SGLT2 and SGLT1 were predicted to be approximately 100% and 0.2%–0.4%, respectively. These analyses suggest that canagliflozin only inhibits SGLT2 in the kidney. Using the simulated proximal tubule luminal concentrations of canagliflozin, the urinary glucose excretion rates in canagliflozin‐treated diabetic patients were accurately predicted using the renal glucose reabsorption model as a PD model. Because the simulation of canagliflozin pharmacokinetics was successful, this PBPK methodology was further validated by successfully simulating the pharmacokinetics of dapagliflozin, another SGLT2 inhibitor. The present results suggest the utility of this PBPK/PD model for predicting canagliflozin concentrations at target sites and help to elucidate the pharmacological effects of SGLT1/2 inhibition in humans. Copyright © 2016 John Wiley & Sons, Ltd.
Thermische Leitfähigkeit von Stahlfaserbeton – eine theoretische Betrachtung
Authors: Fessel Dustin , Simon Peter , Guder Tom , Dehn Frank 
Published: September 2016

AbstractFür die Bemessung von Stahlbeton‐ und Spannbetontragwerken im Brandfall ist die Kenntnis der thermischen Leitfähigkeit λc des Betons eine der wesentlichen Eingangsgrößen. Im Fall der Zugabe von Stahlfasern zum Beton gibt es bislang widersprüchliche Aussagen, inwieweit sich diese auf die thermische Leitfähigkeit und somit auf den Feuerwiderstand auswirkt. Vor diesem Hintergrund wurden experimentell ermittelte und in der Literatur dokumentierte Untersuchungsergebnisse ausgewertet und systematisch durch eigene theoretische Betrachtungen sowie anhand eines computergestützten Evaluationsverfahrens ergänzt. Unter der Annahme der Gültigkeit der in DIN EN 1992‐1‐2:2010 angegebenen temperaturabhängigen Unter‐ und Obergrenze für die thermische Leitfähigkeit, auf der Grundlage theoretischer Betrachtungen zum Wärmewiderstand von Beton sowie anhand von Vergleichsrechnungen mittels eines numerischen Modells konnte gezeigt werden, dass sich für in der Praxis übliche Stahlfasergehalte von bis zu 1 Vol.‐% eine vernachlässigbare Änderung der thermischen Leitfähigkeit gegenüber normal‐ und hochfesten Betonen ohne Stahlfasern ergibt. Für andere Betonarten, die sich insbesondere hinsichtlich Betonrohdichte, Art, Größe und Anordnung von Poren sowie bzgl. des physikalischen und chemischen Wasserbindevermögens von normal‐ und hochfestem Beton unterscheiden, sollten jedoch gesonderte Betrachtungen angestellt werden.
Solution and solid state conformational preferences of a family of cyclic disulphide bridged tetrapeptides
Authors: Berger Nadja , Li Fee , Mallick Bert , Brüggemann J. Thomas , Sander Wolfram , Merten Christian 
Published: September 2016

AbstractA set of cyclic tetrapeptides of the general form cyclo (Boc‐Cys‐Pro‐X‐Cys‐OMe) with X being L‐/D‐Ala, L‐/D‐Val, and L‐/D‐Trp was synthesized. These peptides serve as model systems for structure elucidation in solution and feature a variety of structural motifs — namely a β‐turn with intramolecular hydrogen bonding interactions, cis/trans isomerism, and a disulphide bond. In this work, we performed a comprehensive structural analysis focussing on their β‐turn conformational preferences using NMR, VCD, and Raman spectroscopy. Our results provide evidence for a strong influence of a single stereocenter on the structures of the peptides whereas solvent polarity does not significantly affect them. Additionally, the solid state conformational preferences were studied by crystal structure analysis. Overall, a general trend for the conformational preferences of this set of peptides can be concluded from the results of the complementary investigations.
Development and validation of a high performance liquid chromatography quantification method of levo‐tetrahydropalmatine and its metabolites in plasma and brain tissues: application to a pharmacokinetic study
Authors: Abdallah Inas A. , Huang Peng , Liu Jing , Lee David Y. , Liu‐Chen Lee‐Yuan , Hassan Hazem E. 
Published: September 2016

AbstractLevo‐tetrahydropalmatine (l‐THP) is an alkaloid isolated from Chinese medicinal herbs of the Corydalis and Stephania genera. It has been used in China for more than 40 years mainly as an analgesic with sedative/hypnotic effects. Despite its extensive use, its metabolism has not been quantitatively studied, nor there a sensitive reliable bioanalytical method for its quantification simultaneously with its metabolites. As such, the objective of this study was to develop and validate a sensitive and selective HPLC method for simultaneous quantification of l‐THP and its desmethyl metabolites l‐corydalmine (l‐CD) and l‐corypalmine (l‐CP) in rat plasma and brain tissues. Rat plasma and brain samples were processed by liquid–liquid extraction using ethyl acetate. Chromatographic separation was achieved on a reversed‐phase Symmetry® C18 column (4.6 × 150 mm, 5 μm) at 25°C. The mobile phase consisted of acetonitrile–methanol–10 mm ammonium phosphate (pH 3) (10:30:60, v/v) and was used at a flow rate of 0.8 mL/min. The column eluent was monitored at excitation and emission wavelengths of 230 and 315 nm, respectively. The calibration curves were linear over the concentration range of 1–10,000 ng/mL. The intra‐ and interday reproducibility studies demonstrated accuracy and precision within the acceptance criteria of bioanalytical guidelines. The validated HPLC method was successfully applied to analyze samples from a pharmacokinetic study of l‐THP in rats. Taken together, the developed method can be applied for bioanalysis of l‐THP and its metabolites in rodents and potentially can be transferred for bioanalysis of human samples.
Modification of an Enzyme Biocatalyst for the Efficient and Selective Oxidative Demethylation of para‐Substituted Benzene Derivatives
Authors: Chao Rebecca R. , Lau Ian C.‐K. , De Voss James J. , Bell Stephen G. 
Published: September 2016

AbstractThe bacterial CYP199A4 enzyme is able to oxidise a narrow range of aromatic acids, which includes 4‐methoxybenzoic acid, efficiently. A serine 244 to aspartate variant was identified with enhanced activity for a wide range of para‐methoxy‐substituted benzenes. Substrates in which the acidic benzoic acid moiety is replaced with a phenol and the amide, aldehyde and bromide analogues were all oxidised with high activity by the S244D mutant (product formation rate >600 nmol nmolCYP−1 min−1) with turnover numbers of up to 20 000. If the carboxylate moiety was modified to a nitro, ketone, boronic acid, hydroxymethyl or nitrile group, these substrates were also oxidised at a significantly higher activity by S244D than the wild‐type enzyme. 3,4‐Dimethoxybenzaldehyde was demethylated selectively and oxidatively to 3‐methoxy‐4‐hydroxybenzaldehyde by the S244D mutant 84‐fold more rapidly than with the wild‐type enzyme. CYP199A4 would have applications in the catalytic regioselective oxidative demethylation of suitably substituted benzene substrates under mild conditions and in the presence of more oxidatively sensitive functional groups, such as an aldehyde.
Selectivity and Lifetime Effects in Zeolite‐Catalysed Baeyer–Villiger Oxidation Investigated in Batch and Continuous Flow
Authors: Yakabi Keiko , Milne Kirstie , Buchard Antoine , Hammond Ceri 
Published: September 2016

AbstractIn this manuscript, we investigate the kinetic, mechanistic and lifetime aspects of the Baeyer–Villiger oxidation of cyclohexanone with Sn‐β as catalyst and H2O2 as oxidant, with the aim of: 1) elucidating the overall reaction network, 2) closing the carbon balance, particularly at high levels of conversion, and 3) examining the intensification of this process in the continuous regime. The results presented herein conclusively demonstrate that this reaction is highly selective for the desired product (ϵ‐caprolactone) only below conversions of 60 %. Above this level of conversion, unavoidable hydrolysis of ϵ‐caprolactone to 6‐hydroxyhexanoic acid is observed, which consumes the desired product and leads to a reduction in catalytic activity through poisoning. By elucidating the reaction network and working under optimised conditions, we show the potential viability of this methodology to operate continuously over a 180 h period, both at high levels of productivity (324 g (cyclohexanone converted) cm−3 (reactor volume) kg−1 (catalyst) h−1) and selectivity (70 % at 60 % conversion). Over 5000 substrate turnovers were observed during this period, an order of magnitude higher than previously noted for this particular catalyst system.
Relation between Hydrogen Evolution and Hydrodesulfurization Catalysis
Authors: Šarić Manuel , Moses Poul Georg , Rossmeisl Jan 
Published: September 2016

AbstractA relation between hydrogen evolution and hydrodesulfurization catalysis was found by density functional theory calculations. The hydrogen evolution reaction and the hydrogenation reaction in hydrodesulfurization share hydrogen as a surface intermediate and, thus, have a common elementary step, which indicates that the same catalyst should perform well for both hydrogen evolution and hydrogenation. If that catalyst also fulfills additional criteria for breaking carbon–sulfur bonds and releasing hydrogen sulfide, it will be a good hydrodesulfurization catalyst. The hydrogen evolution reaction is normally performed at room temperature and standard pressure, whereas the hydrodesulfurization reaction is driven by high temperature and pressure. Owing to the very different operating conditions, the adsorption free energy of hydrogen differs between hydrodesulfurization and the hydrogen evolution reaction, which makes the connection between the two less obvious.
Synthesis and Deprotonation of Aminophosphane Complexes: First K/N(H)R Phosphinidenoid Complexes and Access to a Complex with a P2N‐Ring Ligand
Authors: Majhi Paresh Kumar , Kyri Andreas Wolfgang , Schmer Alexander , Schnakenburg Gregor , Streubel Rainer 
Published: September 2016

AbstractSynthesis of 1,1′‐bifunctional aminophosphane complexes 3 a–e was achieved by the reaction of Li/Cl phosphinidenoid complex 2 with various primary amines (R=Me, iPr, tBu, Cy, Ph). Deprotonation of complex 3 a (R=Me) with potassium hexamethyldisilazide yielded a mixture of K/NHMe phosphinidenoid complex 4 a and potassium phosphanylamido complex 4 a′. Treatment of complex 3 c (R=tBu) and e (R=Ph) with KHMDS afforded the first examples of K/NHR phosphinidenoid complexes 4 c and e. The reaction of complex 3 c with 2 molar equivalents of KHMDS followed by PhPCl2 afforded complexes 5 c,c′, which possess a P2N‐ring ligand. All complexes were characterized by NMR, IR, MS, and microanalysis, and additionally, complexes 3 b–e and 5 c′ were scrutinized by single‐crystal X‐ray crystallography.
Site‐Specific Isotope‐Labeling of Inosine Phosphoramidites and NMR Analysis of an Inosine‐Containing RNA Duplex
Authors: Dallmann Andre , Beribisky Alexander V. , Gnerlich Felix , Rübbelke Martin , Schiesser Stefan , Carell Thomas , Sattler Michael 
Published: September 2016

AbstractStructural features and internal dynamics of inosine‐containing RNAs are poorly understood. NMR studies of such RNAs require 13C,15N‐labeling, which cannot be achieved using in vitro transcription as inosine and guanosine are not distinguished by RNA polymerase. Herein, we report the synthesis of an inosine phosphoramidite with selective 13C8 and 15N7‐isotope incorporation in the base and uniform 13C‐labeling of the ribose. Chemical synthesis of an RNA duplex containing four consecutive IU base pairs with this optimized isotope‐labeling scheme greatly simplifies NMR spectra and resolves signal overlap. The absence of detectable NMR signals of imino protons and unusual inter‐residue NOE correlations in this RNA indicate deviations from standard A‐form geometry, consistent with reduced stability of this duplex seen in UV melting studies compared to its nonedited RNA counterparts. These studies indicate that the introduction of IU base pairs distorts and destabilizes RNA helices significantly compared to the also noncanonical GU base‐pairs. Our optimized isotope‐labeling scheme enables high‐resolution NMR studies of inosine‐edited RNAs.
Chirality Relay in 2,2′‐Substituted 1,1′‐Binaphthyl: Access to Propeller Chirality of the Tricoordinate Boron Center
Authors: Wang Chen , Sun Zuo‐Bang , Xu Qing‐Wen , Zhao Cui‐Hua 
Published: September 2016

AbstractIt is a challenging issue to achieve propeller chirality for triarylboranes owing to the low transition barrier between the P and M forms of the boron center. Herein, we report a new strategy to achieve propeller chirality of triarylboranes. It was found that the chirality relay from axially chiral 1,1′‐binaphthyl to propeller chirality of the trivalent boron center can be realized when a Me2N and a Mes2B group (Mes=mesityl) are introduced at the 2,2′‐positions of the 1,1′‐binaphthyl skeleton (BN‐BNaph) owing to the strong π–π interaction between the Me2N‐bonded naphthyl ring and the phenyl ring of one adjacent Mes group, which not only exerts great steric hindrance on the rotation of the two Mes groups but also gives unequal stability to the two configurations of the boron center for a given configuration of the binaphthyl moiety. The stereostructures of the boron center were fully characterized through 1H NMR spectroscopy, X‐ray crystal analyses, and theoretical calculations. Detailed comparisons with the analog BN‐Ph‐BNaph, in which the Mes2B group is separated from 1,1′‐binaphthyl by a para‐phenylene spacer, confirmed the essential role of π–π interaction for the successful chirality relay in BN‐BNaph.
Production of Pure Aqueous 13C‐Hyperpolarized Acetate by Heterogeneous Parahydrogen‐Induced Polarization
Authors: Kovtunov Kirill V. , Barskiy Danila A. , Shchepin Roman V. , Salnikov Oleg G. , Prosvirin Igor P. , Bukhtiyarov Andrey V. , Kovtunova Larisa M. , Bukhtiyarov Valerii I. , Koptyug Igor V. , Chekmenev Eduard Y. 
Published: September 2016

AbstractA supported metal catalyst was designed, characterized, and tested for aqueous phase heterogeneous hydrogenation of vinyl acetate with parahydrogen to produce 13C‐hyperpolarized ethyl acetate for potential biomedical applications. The Rh/TiO2 catalyst with a metal loading of 23.2 wt % produced strongly hyperpolarized 13C‐enriched ethyl acetate‐1‐13C detected at 9.4 T. An approximately 14‐fold 13C signal enhancement was detected using circa 50 % parahydrogen gas without taking into account relaxation losses before and after polarization transfer by magnetic field cycling from nascent parahydrogen‐derived protons to 13C nuclei. This first observation of 13C PHIP‐hyperpolarized products over a supported metal catalyst in an aqueous medium opens up new possibilities for production of catalyst‐free aqueous solutions of nontoxic hyperpolarized contrast agents for a wide range of biomolecules amenable to the parahydrogen induced polarization by side arm hydrogenation (PHIP‐SAH) approach.
Asymmetric Synthesis of an Amino Acid Derivative from Achiral Aroyl Acrylamide by Reversible Michael Addition and Preferential Crystallization
Authors: Kaji Yuki , Uemura Naohiro , Kasashima Yoshio , Ishikawa Hiroki , Yoshida Yasushi , Mino Takashi , Sakamoto Masami 
Published: September 2016

AbstractSingle‐handed α‐amino acid derivatives were generated from achiral precursors without an external chiral source. Conjugate addition of phenethylamine to an achiral aroyl acrylamide under homogeneous conditions gave the α‐amino amides in quantitative yields, which crystallized as a conglomerate of a P21 crystal system. Dynamic preferential crystallization or attrition‐enhanced deracemization resulted in the formation of enantiomorphic crystals of 99 % ee.
ChemInform Abstract: Enclathration of X@La4 Tetrahedra in Channels of Zn—P Frameworks in La3Zn4P6X (X: Cl, Br).
Authors: Wang Jian , Kaseman Derrick , Lee Kathleen , Sen Sabyasachi , Kovnir Kirill 
Published: September 2016

AbstractPhase‐pure polycrystalline La3Zn4P6Cl (I) and La3Zn4P6.6Br0.8 (II) are prepared by solid state reactions of stoichiometric amounts of La, Zn, red P, and anhydrous ZnCl2 (ZnBr2) (glassy carbon crucibles in evacuated silica tubes, 1073 K, 6 d).
ChemInform Abstract: A Deep‐Ultraviolet Nonlinear Optical Crystal: Strontium Beryllium Borate Fluoride with Planar Be(O/F)3 Groups.
Authors: Yu Na , Wang Shichao , Ye Ning , Liang Fei , Lin Zheshuai , Luo Min , Poeppelmeier Kenneth R. 
Published: September 2016

AbstractSingle crystals of Sr3 [(Be0.3B0.7)3B3O10] [Be(O0.7F0.3)3] (I) are grown by spontaneous crystallization of a molten SrO/B2O3/LiF flux using a 3:1:3:5 molar mixture of SrCO3, BeO, B2O3, and LiF (Pt crucible, 950 °C; rapid cooling to 800 °C at a rate of 50 °C/h and further cooling to 700 °C at a rate of 3 °C/h).
ChemInform Abstract: Structural, Magnetic and Theoretical Investigations on the Magnetocaloric Properties of La0.7Sr0.25K0.05MnO3 Perovskite.
Authors: El Kossi S. , Dhahri J. , Hlil E. K. 
Published: September 2016

AbstractThe title compound is synthesized by solid state reaction of La2O3, SrCO3, K2CO3, and MnO2 (calcination at 900—1100 °C, sintering at 1200 °C for 24 h).
ChemInform Abstract: Lithiation‐Driven Structural Transition of VO2F into Disordered Rock‐Salt LixVO2F.
Authors: Chen Ruiyong , Maawad Emad , Knapp Michael , Ren Shuhua , Beran Premysl , Witter Raiker , Hempelmann Rolf 
Published: September 2016

AbstractRhombohedral VO2F (space group R$\bar 3$c) is synthesized as a new high capacity/energy density cathode material for rechargeable Li‐batteries by ball‐milling of stoichiometric mixtures of VOF3 and V2O5.