bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a New Susceptibility Locus for Systemic Lupus Erythematosus on Chromosome 12 in Individuals of European Ancestry
Authors: Demirci F. Yesim , Wang Xingbin , Kelly Jennifer A. , Morris David L. , Barmada M. Michael , Feingold Eleanor , Kao Amy H. , Sivils Kathy L. , Bernatsky Sasha , Pineau Christian , Clarke Ann E. , Ramsey‐Goldman Rosalind , Vyse Timothy J. , Gaffney Patrick M. , Manzi Susan , Kamboh M. Ilyas 
Published: August 2015

ObjectiveGenome‐wide association studies (GWAS) in individuals of European ancestry identified a number of systemic lupus erythematosus (SLE) susceptibility loci using earlier versions of high‐density genotyping platforms. Followup studies on suggestive GWAS regions using larger samples and more markers identified additional SLE loci in subjects of European descent. This multistage study was undertaken to identify novel SLE loci.MethodsIn stage 1, we conducted a new GWAS of SLE in a North American case–control sample of subjects of European ancestry (n = 1,166) genotyped on Affymetrix Genome‐Wide Human SNP Array 6.0. In stage 2, we further investigated top new suggestive GWAS hits by in silico evaluation and meta‐analysis using an additional data set of subjects of European descent (>2,500 individuals), followed by replication of top meta‐analysis findings in another data set of subjects of European descent (>10,000 individuals) in stage 3.ResultsAs expected, our GWAS revealed the most significant associations at the major histocompatibility complex locus (6p21), which easily surpassed the genome‐wide significance threshold (P < 5 × 10−8). Several other SLE signals/loci previously implicated in Caucasians and/or Asians were also confirmed in the stage 1 discovery sample, and the strongest signals were observed at 2q32/STAT4 (P = 3.6 × 10−7) and at 8p23/BLK (P = 8.1 × 10−6). Stage 2 meta‐analyses identified a new genome‐wide significant SLE locus at 12q12 (meta P = 3.1 × 10−8), which was replicated in stage 3.ConclusionOur multistage study identified and replicated a new SLE locus that warrants further followup in additional studies. Publicly available databases suggest that this newly identified SLE signal falls within a functionally relevant genomic region and near biologically important genes.
Brief Report: Pulmonary Function Tests: High Rate of False‐Negative Results in the Early Detection and Screening of Scleroderma‐Related Interstitial Lung Disease
Authors: Suliman Yossra A. , Dobrota Rucsandra , Huscher Dörte , Nguyen‐Kim Thi D. L. , Maurer Britta , Jordan Suzana , Speich Rudolf , Frauenfelder Thomas , Distler Oliver 
Published: August 2015

ObjectiveValidated methods for the screening and early diagnosis of systemic sclerosis (SSc; scleroderma)–related interstitial lung disease (ILD) are needed. The aim of this study was to evaluate the performance of pulmonary function tests (PFTs) compared with that of high‐resolution computed tomography (HRCT) of the chest for the detection of SSc‐related ILD in clinical practice, and to identify predictors of lung involvement that is functionally occult but significant on HRCT.MethodsProspectively enrolled patients with SSc were assessed according to the European League Against Rheumatism (EULAR)/EULAR Scleroderma Trial and Research standards. The assessment included PFTs and HRCT. The HRCT images were evaluated in a blinded manner by 2 experienced radiologists. The performance parameters of PFTs for the diagnosis of SSc‐related ILD were calculated. Predictors of significant ILD as determined by HRCT in patients with normal forced vital capacity (FVC) values were identified through logistic regression.ResultsAmong the 102 patients, 64 (63.0%) showed significant ILD on HRCT, while only 27 (26.0%) had an FVC <80% of predicted, and 54 (53.0%) had a decrease in the results of at least 1 PFT. Forty (62.5%) of 64 patients with significant ILD on HRCT had a normal FVC value, translating into a high false‐negative rate. Notably, 5 of 40 patients with a normal FVC value had severe, functionally occult lung fibrosis; in 2 of these patients, the results of all of the PFTs were within normal limits. Patients with normal FVC values despite evidence of fibrosis on HRCT more frequently had anti–Scl‐70 antibodies and diffuse SSc and less frequently had anticentromere antibodies (ACAs) compared with patients with both normal FVC values and normal HRCT results.ConclusionThe derived evidence‐based data reveal a high risk of missing significant SSc‐related ILD when relying solely on PFTs. More comprehensive screening algorithms for early detection are warranted. In particular, additional imaging investigations for the early detection of SSc‐related ILD should be considered in ACA‐negative patients with normal FVC values.
Involvement of Mast Cells in α7 Nicotinic Receptor Agonist Exacerbation of Freund's Complete Adjuvant–Induced Monoarthritis in Mice
Authors: Lopes Fernando , Graepel Rabea , Reyes Jose Luis , Wang Arthur , Petri Björn , McDougall Jason J. , Sharkey Keith A. , McKay Derek M. 
Published: August 2015

Objective Activation of antiinflammatory cholinergic (vagal) pathways can reduce inflammation, and in vitro studies support a pivotal role of α7 nicotinic acetylcholine receptors (α7‐nAChR), macrophages, and T cells in these events. The aim of this study was to assess α7‐nAChR agonists as an antiinflammatory treatment for Freund's complete adjuvant (CFA)–induced monoarthritis.MethodsArthritis was induced by intraarticular injection of CFA unilaterally into the knee joints of mice. Animals were treated with α7‐nAChR agonists (AR‐R17779 or A844606), with or without antagonists (COG133 or methyllycaconitine), and joint inflammation and pain were assessed. Experiments were repeated in c‐KitW‐sh mast cell–deficient mice, and the effects of an α7‐nAChR agonist on mast cell proliferation, migration, and activation by lipopolysaccharide (LPS) were tested.ResultsTreatment with α7‐nAChR agonists significantly exacerbated CFA‐induced arthritis and pain, as gauged by all indices of assessment, the specificity of which was confirmed by coadministration of an nAChR antagonist that attenuated the increase in disease severity. Toluidine blue–positive mast cells were increased in the joint capsule of CFA plus AR‐R17779–treated mice, and AR‐R17779 enhanced LPS‐induced TNF proliferation and migration of a human mast cell line. The AR‐R17779–driven increase in severity of CFA‐induced arthritis was significantly reduced in mast cell–deficient mice.ConclusionUsing CFA to elicit a local inflammatory response, we found that pharmacologic activation of α7‐nAChR exacerbated joint inflammation and pain, in part via mast cells, which illustrates the organ‐ and disease‐specific nature of regulatory neuroimmune mechanisms. Thus, α7‐nAChR activation may not be uniformly antiinflammatory in all types of inflammatory joint disease.
A Novel Allyl Transfer Coupled with a Grob Fragmentation
Authors: Li Shao‐Gang , Chen Hui‐Jun , Yang Yang‐Yang , Wu Wen‐Ju , Wu Yikang 
Published: August 2015

AbstractA novel acid‐promoted rearrangement is disclosed. In the previously unknown transformation, an allyl group migrated to an in situ formed carbocation stabilized by an electron‐rich aryl or heteroaryl group, resulting in a stereoselective intramolecular Grob fragmentation. The outcome of the rearrangement observed with an array of substrates can be satisfactorily rationalized using a working hypothesis with the aid of a six‐membered transition state similar to those proposed for the anionic oxy‐Cope or oxonia‐Cope rearrangements, but involving only one instead of two double bonds.
Improved stereoselective bioreduction of t‐butyl 6‐cyano‐(5R)‐hydroxy‐3‐oxohexanoate by Rhodotorula glutinis through heat treatment
Authors: Luo Xi , Wang Ya‐Jun , Zheng Yu‐Guo 
Published: August 2015

AbstractOptically pure t‐butyl 6‐cyano‐(3R, 5R)‐dihydroxyhexanoate ((R)‐1b) is the key precursor for atorvastatin calcium, the most widely used cholesterol‐lowering drug. In this work, a strain ZJB‐09224 capable of asymmetrically reducing t‐butyl 6‐cyano‐(5R)‐hydroxy‐3‐oxohexanoate (1a) to corresponding optically pure (R)‐1b was successfully isolated from soil sample, identified belonging to Rhodotorula glutinis based on the morphology, physiological tests, and the 18S rDNA sequence analysis. It was found that heat treatment of cell suspension at 45 °C for 25 Min significantly improved R. glutinis ZJB‐09224 stereoselectivity. The asymmetric bioreduction of 1a was most efficient at pH 7.5, 35 °C, 50 mM (15.0 g L−1) substrate concentration, 40.0 g DCW L−1 cell loading size, 0.54 M (60.0 g L−1) sodium lactate acting as co‐substrate. Under these optimal conditions, 0.046 M (R)‐1b was produced with de (diastereomeric excess) value of 99.2% after 40 H conversion. Moreover, R. glutinis ZJB‐09224 has a broad substrate spectrum, making it a potential tool for some valuable chiral alcohol pharmaceutical intermediates synthesis.
Species‐ and gender‐dependent differences in the glucuronidation of a flavonoid glucoside and its aglycone determined using expressed UGT enzymes and microsomes
Authors: Dai Peimin , Luo Feifei , Wang Ying , Jiang Huangyu , Wang Liping , Zhang Guiyu , Zhu Lijun , Hu Ming , Wang Xinchun , Lu Linlin , Liu Zhongqiu 
Published: August 2015

AbstractFlavonoids occur naturally as glucosides and aglycones. Their common phenolic hydroxyl groups may trigger extensive UDP‐glucuronosyltransferase (UGT)‐ catalysed metabolism. Unlike aglycones, glucosides contain glucose moieties. However, the influence of these glucose moieties on glucuronidation of glucosides and aglycones remains unclear. In this study, the flavonoid glucoside tilianin and its aglycone acacetin were used as model compounds. The glucuronidation characteristics and enzyme kinetics of tilianin and acacetin were compared using human UGT isoforms, liver microsomes and intestinal microsomes obtained from different animal species. Tilianin and acacetin were metabolized into different glucuronides, with UGT1A8 produced as the main isoform. Assessment of enzyme kinetics in UGT1A8, human liver microsomes and human intestinal microsomes revealed that compared with tilianin, acacetin displayed lower Km (0.6‐, 0.7‐ and 0.6‐fold, respectively), higher Vmax (20‐, 60‐ and 230‐fold, respectively) and higher clearance (30‐, 80‐ and 300‐fold, respectively). Furthermore, glucuronidation of acacetin and tilianin showed significant species‐ and gender‐dependent differences. In conclusion, glucuronidation of flavonoid aglycones is faster than that of glucosides in the intestine and the liver. Understanding the metabolism and species‐ and gender‐dependent differences between glucosides and aglycones is crucial for the development of drugs from flavonoids. Copyright © 2015 John Wiley & Sons, Ltd.
Probabilistic Inferences Under Emotional Stress: How Arousal Affects Decision Processes
Authors: Wichary Szymon , Mata Rui , Rieskamp Jörg 
Published: August 2015

AbstractMany models of decision making neglect emotional states that could affect individuals' cognitive processes. The present work explores the effect of emotional stress on people's cognitive processes when making probabilistic inferences. Two contrasting hypotheses are tested against one another: the uncertainty‐reduction and attention‐narrowing hypotheses of how emotional stress affects decision making. In the experimental study, emotional stress was induced through the use of highly aversive pictures immediately before each decision. Emotional state was assessed by both subjective (state anxiety, arousal, and pleasantness ratings) and objective (skin conductance) measures. The results show that emotional stress impacts decision making; in particular, emotionally aroused participants seem to have focused on the most important information and selected simpler decision strategies relative to participants in a control condition. The results are in line with the attention‐narrowing hypothesis and suggest that emotional stress can impact decision making through limited predecisional information search and the selection of simpler decision strategies. Copyright © 2015 John Wiley & Sons, Ltd.
Human Acid β‐Glucosidase Inhibition by Carbohydrate Derived Iminosugars: Towards New Pharmacological Chaperones for Gaucher Disease
Authors: Parmeggiani Camilla , Catarzi Serena , Matassini Camilla , D'Adamio Giampiero , Morrone Amelia , Goti Andrea , Paoli Paolo , Cardona Francesca 
Published: August 2015

AbstractA collection of carbohydrate‐derived iminosugars belonging to three structurally diversified sub‐classes (polyhydroxylated pyrrolidines, piperidines, and pyrrolizidines) was evaluated for inhibition of human acid β‐glucosidase (glucocerebrosidase, GCase), the deficient enzyme in Gaucher disease. The synthesis of several new pyrrolidine analogues substituted at the nitrogen or α‐carbon atom with alkyl chains of different lengths suggested an interpretation of the inhibition data and led to the discovery of two new GCase inhibitors at sub‐micromolar concentration. In the piperidine iminosugar series, two N‐alkylated derivatives were found to rescue the residual GCase activity in N370S/RecNcil mutated human fibroblasts (among which one up to 1.5‐fold). This study provides the starting point for the identification of new compounds in the treatment of Gaucher disease.
Scaffold‐Hopping of Multicationic Amphiphiles Yields Three New Classes of Antimicrobials
Authors: Mitchell Myles A. , Iannetta Anthony A. , Jennings Megan C. , Fletcher Madison H. , Wuest William M. , Minbiole Kevin P. C. 
Published: August 2015

AbstractQuaternary ammonium compounds (QACs) are a vital class of antiseptics. Recent investigations into their construction are uncovering novel and potent multicationic variants. Based on a trisQAC precedent, we have implemented a scaffold‐hopping approach to develop alternative QAC architectures that display 1–3 long alkyl chains in specific projections from cyclic and branched core structures bearing 3–4 nitrogen atoms. The preparation of 30 QAC structures allowed for correlation of scaffold structure with antimicrobial activity. We identified QACs with limited conformational flexibility that have improved bioactivity against planktonic bacteria as compared to their linear counterparts. We also confirmed that resistance, as evidenced by an increased minimum inhibitory concentration (MIC) for methicillin‐resistant Staphylococcus aureus (MRSA) compared to methicillin‐susceptible Staphylococcus aureus (MSSA), can reduce efficacy up to 64‐fold for monocationic QACs. Differentiation of antimicrobial and anti‐biofilm activity, however, was not observed, suggesting that these compounds utilize a non‐specific mode of eradication.
Abnormal expression of DNA methyltransferases and genomic imprinting in cloned goat fibroblasts
Authors: Wan Yongjie , Deng Mingtian , Zhang Guomin , Ren Caifang , Zhang Hao , Zhang Yanli , Wang Lizhong , Wang Feng 
Published: August 2015

AbstractSomatic cell nuclear transfer (SCNT) is a useful way to produce cloned animals. However, SCNT animals exhibit DNA methylation and genomic imprinting abnormalities. These abnormalities may be due to the faulty epigenetic reprogramming of donor cells. To investigate the consequence of SCNT on the genomic imprinting and global methylation in the donor cells, growth patterns and apoptosis of cloned goat fibroblast cells (CGFCs) at passage 7 were determined. Growth patterns in CGFCs were similar to the controls; however, the growth rate in log phase was lower and apoptosis in CGFCs were significantly higher (P < 0.01). In addition, quantitative expression analysis of three DNA methyltransferases (Dnmt) and two imprinted genes (H19, IGF2R) was conducted in CGFCs: Dnmt1 and Dnmt3b expression was significantly reduced (P < 0.01), and H19 expression was decreased sixfold (P < 0.01); however, the expression of Dnmt3a was unaltered and IGF2R expression was significantly increased (P < 0.05). Finally, we used bisulfite sequencing PCR to compare the DNA methylation patterns in differentially methylated regions (DMRs) of H19 and IGF2R. The DMRs of H19 (P < 0.01) and IGF2R (P < 0.01) were both highly methylated in CGFCs. These results indicate that the global genome might be hypomethylated. Moreover, there is an aberrant expression of imprinted genes and DMR methylation in CGFCs.
Diversity‐Oriented Synthesis through Rh‐Catalyzed Selective Transformations of a Novel Multirole Directing Group
Authors: Su Bo , Wei Jiang‐bo , Wu Wen‐lian , Shi Zhang‐jie 
Published: August 2015

AbstractIn the context of transition‐metal‐catalyzed CH functionalization, directing‐group strategy was developed for the improvement of chemical reactivity and selectivity. Recently, to avoid the inherent limitations of traditional mono‐role directing groups, a dual‐role oxidizing‐directing‐group strategy was developed, in which the directing group acts both as directing group and oxidant. Herein, we report a multirole directing group, which possesses multiple reactive sites, exhibits unique reactivity and selectivity, and leads to four different types of products from a single starting material through rhodium‐catalyzed CH activation/alkyne annulation reactions. The excellent product diversity and regio‐ and redox selectivity were well controlled by the tuning of solvents and oxidants.
Recent Advances in the Synthesis and Electrocatalytic Applications of Platinum‐Based Bimetallic Alloy Nanostructures
Authors: Lai Jianping , Luque Rafael , Xu Guobao 
Published: August 2015

AbstractPt‐based bimetallic alloy nanomaterials with a low Pt loading can exhibit promising catalytic properties with exciting electrochemical applications. An effective structure control of Pt‐based bimetallic alloy nanomaterials is critical to achieve enhanced catalytic properties. This review article focuses on recent advances in the controllable synthesis and electrocatalytic applications of Pt‐based bimetallic alloy nanostructures. Recent contributions on the controllable synthesis of a rich variety of Pt‐based bimetallic alloy nanostructures, for example, PtPd, PtCu, PtNi, PtCo, and PtFe, and hybrid nanostructures based on Pt‐based bimetallic alloy nanomaterials are summarized. Different Pt‐based bimetallic alloy nano‐electrocatalysts with enhanced activity and durability for different electrocatalytic reactions, such as the fuel cell reaction and the hydrogen evolution reaction, are outlined. Finally, an outlook on future trends and developments is provided.
Black Titania for Superior Photocatalytic Hydrogen Production and Photoelectrochemical Water Splitting
Authors: Zhu Guilian , Yin Hao , Yang Chongyin , Cui Houlei , Wang Zhou , Xu Jijian , Lin Tianquan , Huang Fuqiang 
Published: August 2015

AbstractTo utilize visible‐light solar energy to meet environmental and energy crises, black TiO2 as a photocatalyst is an excellent solution to clean polluted air and water and to produce H2. Herein, black TiO2 with a crystalline core–amorphous shell structure reduced easily by CaH2 at 400 °C is demonstrated to harvest over 80 % solar absorption, whereas white TiO2 harvests only 7 %, and possesses superior photocatalytic performances in the degradation of organics and H2 production. Its water decontamination is 2.4 times faster and its H2 production was 1.7 times higher than that of pristine TiO2. Photoelectrochemical measurements reveal that the reduced samples exhibit greatly improved carrier densities, charge separation, and photocurrent (a 4.5‐fold increase) compared with the original TiO2. Consequently, this facile and versatile method could provide a promising and cost‐effective approach to improve the visible‐light absorption and performance of TiO2 in photocatalysis.
Hierarchically Structured MnO2‐Co/C Nanocomposites: Highly Efficient and Magnetically Recyclable Catalysts for the Aerobic Oxidation of Alcohols
Authors: Zhi Jian , Mitchell Sharon , Pérez‐Ramírez Javier , Reiser Oliver 
Published: August 2015

AbstractPorous MnO2 microspheres distributed around magnetic carbon‐coated cobalt nanoparticles were developed. The performance of these nanoparticles rivals that of Pd‐based catalysts for the selective oxidation of alcohols. Excellent recyclability was conveniently achieved by magnetic decantation and is demonstrated in ten consecutive cycles with no apparent material or performance losses.
Enhanced Visible‐Light Photoelectrocatalytic Activity of {001}TiO2 Electrodes Assisted with Carbon Quantum Dots
Authors: Zhang Ya‐nan , Tian Hongyi , Zhao Guohua 
Published: August 2015

AbstractAiming at further developing the application of highly reactive {001}TiO2 in photoelectrocatalytic oxidation, which is only limited by its response in UV light, carbon quantum dots (CQDs) are introduced to provide the excitation sources for {001}TiO2 through upconversion from visible to UV light. The CQDs/{001}TiO2 photoelectrode is prepared by loading the CQDs on truncated square pyramid‐shaped TiO2 spheres exposed to high‐activity {001} facets, using a simple impregnation–drying method. The results indicate that the CQDs/{001}TiO2 possess enhanced photoelectrocatalytic ability with an increased photocurrent of 12 mA cm−2 and photocurrent decay time of 1.75 s. Compared with pure {001}TiO2, the surface photochemical reaction resistance of CQDs/{001}TiO2 decreases, whereas the number of photogenerated carriers increase greatly. This visible‐light photoelectrocatalytic activity results from the synergistic effect of CQDs and the {001} facet of anatase TiO2.
Electrospinning Synthesis of Porous CoWO4 Nanofibers as an Ultrasensitive, Nonenzymatic, Hydrogen‐Peroxide‐Sensing Interface with Enhanced Electrocatalysis
Authors: Liao Sheng‐Hui , Lu Shi‐Yu , Bao Shu‐Juan , Yu Ya‐Nan , Yu Ling 
Published: August 2015

AbstractIn this work, porous WO3, Co3O4, and CoWO4 nanofibers (NFs) were fabricated by using an electrospinning technique followed by high‐temperature calcination. The different NFs were used to modify biosensor electrodes and detect H2O2 without the help of an enzyme. The electrochemical results indicated that the CoWO4 NF‐based sensor presented a remarkable electrocatalytic activity towards H2O2 oxidation, including lower redox potential, lower detection limit, fast response, as well as the widest linear range among our designed biosensors of this type. Furthermore, we found that the ideal test potential of a nonenzymatic biosensor is closely dependent on the composition of the detected electrode surface, and the test potential has a great effect on the detection linear range of nanomaterial‐based biosensors. The results of this work provide a new way to explore excellent nanomaterials for modifying nonenzymatic biosensor electrodes.
Highly Stable PEMFC Electrodes Based on Electrospun Antimony‐Doped SnO2
Authors: Cavaliere Sara , Jiménez‐Morales Ignacio , Ercolano Giorgio , Savych Iuliia , Jones Deborah , Rozière Jacques 
Published: August 2015

AbstractHigh durability and activity for the oxygen reduction reaction were demonstrated for oxide‐supported platinum catalysts. The supports were antimony‐doped SnO2 (ATO) fibres‐in‐tubes obtained by electrospinning and subsequent calcination. The doping with antimony instead of the already‐reported niobium, allowed the preparation of tin oxide with electrical conductivity that was similar to carbon, which also had an increased electrocatalyst loading. Platinum nanoparticles supported on electrospun ATO demonstrated higher electrochemical stability and comparable mass activity to commercial Pt/C during ex situ potential cycling. The in situ fuel cell tests also revealed improved corrosion resistance with no noticeable degradation of the oxide‐based membrane electrode assembly (MEA), but a slightly lower performance compared to the MEA with carbon‐supported catalysts.