bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of eleutheroside B metabolites derived from an extract of Acanthopanax senticosus Harms by high‐resolution liquid chromatography/quadrupole time‐of‐flight mass spectrometry and automated data analysis
Authors: Lu Fang , Sun Qiang , Bai Yun , Bao Shunru , Li Xuzhao , Yan Guangli , Liu Shumin
Published: January 2012

We elucidated the structure and metabolite profile of eleutheroside B, a component derived from the extract of Acanthopanax senticosus Harms, after oral administration of the extract in rats. Samples of rat plasma were collected and analyzed by selective high‐resolution liquid chromatography/quadrupole time‐of‐flight mass spectrometry (UPLC/Q‐TOF MS) automated data analysis method. A total of 11 metabolites were detected: four were identified, and three of those four are reported for the first time here. The three new plasma metabolites were identified on the basis of mass fragmentation patterns and literature reports. The major in vivo metabolic processes associated with eleutheroside B in A. senticosus include demethylation, acetylation, oxidation and glucuronidation after deglycosylation. A fairly comprehensive metabolic pathway was proposed for eleutheroside B. Our results provide a meaningful basis for drug discovery, design and clinical applications related to A. senticosus in traditional Chinese medicine. Copyright © 2012 John Wiley & Sons, Ltd.
A liquid chromatography–tandem mass spectrometry assay for the determination of nemonoxacin (TG‐873870), a novel nonfluorinated quinolone, in human plasma and urine and its application to a single‐dose pharmacokinetic study in healthy Chinese volunteers
Authors: Guo Beining , Zhang Jing , Yu Jicheng , Wu Xiaojie , Shi Yaoguo , Tsai Cheng‐Yuan
Published: January 2012

Nemonoxacin (TG‐873870) is a novel C‐8‐methoxy nonfluorinated quinolone with higher activity than ciprofloxacin, levofloxacin and moxifloxacin against Gram‐positive pathogens including methicillin‐susceptible or methicillin‐resistant Staphylococcus aureus and Streptococcus pneumoniae with various resistant phenotypes. A rapid, sensitive and selective liquid chromatography–tandem mass spectrometric (LC‐MS/MS) method was developed and validated to determine the concentration of nemonoxacin in human plasma and urine. Protein precipitation and liquid–liquid extraction were employed for plasma and urine sample preparations, respectively, and extract was then injected into the system. Separation was performed on a C18 reversed‐phase column using acetonitrile–0.1% formic acid as a mobile phase. Both analyte and internal standard (gatifloxacin) were determined using electrospray ionization and the MS data acquisition via the selected reaction monitoring in positive‐ion mode. The lower limit of quantification was 5 ng/mL and the calibration curves were linear in the concentration range of 5–1000 ng/mL. The accuracy, precision, selectivity, linearity, recovery, matrix effect and stability were validated for TG‐873870 in human plasma and urine. The method was successfully applied to a pharmacokinetic study enrolling 12 healthy Chinese volunteers administered nemonoxacin malate capsules. Copyright © 2012 John Wiley & Sons, Ltd.
Buffered Aluminum Chloride as a Highly Efficient Cocatalyst for Olefin Dimerization and Polymerization
Authors: Dötterl Matthias , Alt Helmut G.
Published: January 2012

A binary cocatalyst system based on simple aluminum chloride and weak Lewis bases such as triphenylbismuth or N‐methylpyrrole has been developed. A donor–acceptor interaction kept aluminum chloride dissolved in toluene or methylene chloride. The systems were investigated by use of 27Al NMR spectroscopy and were used as cocatalysts in nickel‐catalyzed dimerization and polymerization reactions of α‐olefins. Their Lewis acidities correlated to the line width of the 27Al NMR signals and were influenced by the solvent and the type and amount of buffer. For propene dimerization reactions, dimer selectivities of up to 95 % were achieved. Ethene was dimerized to give butenes (up to 92 %), of which 79 % were 1‐butene. With a Brookhart‐type nickel diimine complex, ethene was polymerized with a cocatalyst solely based on aluminum chloride. Up to 38 wt % of the reaction products were polyethylene with a typical molecular weight of 140 kg mol−1. The donor–acceptor interactions of triphenylbismuth and N‐methylpyrrole with aluminum chloride were successfully transferred to Lewis acidic chloroaluminate ionic liquids. Ethene was polymerized with a nickel diimine complex dissolved in buffered chloroaluminate ionic liquids in the absence of alkylaluminum groups.
Chemistry of Cobalt(II) Confined in the Pores of Ordered Silica Monoliths: From the Formation of the Monolith to the CoFe Prussian Blue Analogue Nanocomposite
Authors: Aouadi Merwen , Fornasieri Giulia , Briois Valérie , Durand Pierrick , Bleuzen Anne
Published: January 2012

Recently we conceived of an original strategy that allows the precipitation of Prussian blue analogues (PBAs) in the ordered pores of silica monoliths to lead to photomagnetic CoFe PBA–silica nanocomposites. To determine the critical parameters and fully control the synthesis of the photoactive CoFe PBA in the pores of the silica matrix, X‐ray absorption spectroscopy was performed at the cobalt K‐edge. This study showed that cobalt cation chemistry is the keystone of the entire process. The local environment and the electronic structure of the cobalt cation undergo several modifications during the formation process: first the incorporation of the cation as an octahedral complex into the ordered block copolymer phase, then the deprotonation by thermohydrolysis to give a fourfold‐coordinated deprotonated lowly condensed species and finally the formation of the 3D coordination network of CoFe PBA in acidic conditions through a rapid reprotonation followed by nucleophilic substitution accompanied by the electronic transfer, thus leading to the photomagnetic CoIII(LS)–FeII(LS) (LS=low spin) pairs.
Efficient Conventional‐ and Inverted‐Type Photovoltaic Cells Using a Planar Alternating Polythiophene Copolymer
Authors: Lee Wonho , Choi Hyosung , Hwang Sungu , Kim Jin Young , Woo Han Young
Published: January 2012

A low‐band‐gap alternating copolymer, poly{5,6‐bis(octyloxy)‐4‐(thiophen‐2‐yl)benzo[c]‐1,2,5‐thiadiazole} (PTBT), was synthesized and investigated for photovoltaic applications. PTBT showed a minimized torsion angle in its main backbone owing to the introduction of solubilizing octyloxy groups on the electron‐poor benzothiadiazole unit, thereby resulting in pronounced intermolecular ordering and a deep level of the HOMO (−5.41 eV). By blending PTBT with [6,6]phenyl‐C61‐butyric acid methyl ester (PC61BM), highly promising performance was achieved with power‐conversion efficiencies (PCEs) of 5.9 and 5.3 % for the conventional and inverted devices, respectively, under air mass 1.5 global (AM 1.5G, 100 mW cm−2) illumination. The open‐circuit voltage (VOC≈0.85–0.87 V) is one of the highest values reported thus far for thiophene‐based polymers (e.g., poly(3‐hexylthiophene) VOC≈0.6 V). The inverted device also achieved a remarkable PCE compared to other devices based on low‐band‐gap polymers. Ideal film morphology with bicontinuous percolation pathways was expected from the atomic force microscopy (AFM) images, space‐charge‐limited current (SCLC) mobility, and selected‐area electron‐diffraction (SAED) measurements. This molecular design strategy is useful for achieving simple, processable, and planar donor–acceptor (D–A)‐type low‐band‐gap polymers with a deep HOMO for applications in photovoltaic cells.
Chiral cinchona alkaloid‐derived thiourea catalyst for enantioselective synthesis of novel β‐amino esters by mannich reaction
Authors: Li Weihua , Song Baoan , Bhadury Pinaki S. , Li Liang , Wang Zhenchao , Zhang Xiaoyan , Hu Deyu , Chen Zhuo , Zhang Yuping , Bai Song , Wu Jian , Yang Song
Published: January 2012

A cinchona alkaloid‐derived thiourea catalyst has been designed to access new asymmetric β‐amino esters bearing benzothiazole moiety by utilizing a Mannich reaction between an imine and a malonate. A simultaneous activation of the two imine functionalities and malonate by the bifunctional chiral organocatalyst is proposed to account for the good yields (71–91%) and high enantiomeric excess (89.4–98.5%) under mild conditions. Chirality © 2012 Wiley Periodicals, Inc.
Enantioselective degradation of hexaconazole in rat hepatic microsomes in vitro
Authors: Zhang Ping , Dang Ziheng , Shen Zhigang , Zhu Wentao , Xu Xinyuan , Liu Donghui , Zhou Zhiqiang
Published: January 2012

Hexaconazole [(RS)‐2‐(2,4‐dichlorophenyl)‐1‐(1H‐1,2,4‐triazol‐1‐yl) hexan‐2‐ol] is a potent triazole fungicide and consists of a pair of enantiomers. Enantioselective degradation of hexaconazole was investigated in rat hepatic microsomes in vitro. Concentrations of (−)‐ and (+)‐hexaconazole and enantiomer fraction were determined by high performance liquid chromatography with a cellulose‐tris‐(3,5‐dimethylphenylcarbamate)‐based chiral stationary phase. The t1/2 of (−)‐hexaconazole and (+)‐hexaconazole were 23.70 and 13.95 min for rac‐ hexaconazole and 44.18 and 23.54 for enantiomers examined separately. Furthermore, hexaconazole is configurationally stable in rat hepatic microsomes, demonstrating no chiral inversion from the (−)‐hexaconazole to (+)‐hexaconazole or vice versa. Intrinsic metabolic clearance of (+)‐hexaconazole is 1.12 times than that of (−)‐hexaconazole. Interaction study revealed that there was competitive inhibition between (−)‐hexaconazole and (+)‐hexaconazole. In addition, there was a significant difference between the inhibitory concentration (IC50) of (−)‐ to (+)‐hexaconazole and (+)‐ to (−)‐hexaconazole [IC50(−)/(+)/IC50(+)/(−) = 1.88]. These results may have potential implications for better environmental and ecological risk assessment for hexaconazole. Chirality, 2012. © 2012 Wiley Periodicals, Inc.
Enantioselective determination of triazole fungice tetraconazole by chiral high‐performance liquid chromatography and its application to pharmacokinetic study in cucumber, muskmelon, and soils
Authors: Li Jing , Dong Fengshou , Xu Jun , Liu Xingang , Li Yuanbo , Shan Weili , Zheng Yongquan
Published: January 2012

A simple chiral high‐performance liquid chromatography method with diode array detector was developed and validated for stereoselective determination of tetraconazole enantiomers in cucumber, muskmelon, and soils. Good separation was achieved at 20°C using cellulose tris‐(4‐methylbenzoate) as chiral stationary phase, a mixture of n‐hexane and ethanol (90:10) as mobile phase at a flow rate of 0.8 ml/min. The assay method was linear over a range of concentrations (0.5–50 μg/ml) and the mean recoveries in all samples were more than 85% for the two enantiomers. The limits of detection for both enantiomers in plant and soil samples were 0.06 and 0.12 μg/g, respectively. Then, the proposed method was successfully applied to the study of enantioselective degradation of rac‐tetraconazole in cucumber, muskmelon, and soils. The results showed that the degradation of two enantiomers of tetraconazole followed first‐order kinetics and significantly stereoselective behavior was observed in cucumber, muskmelon, and Beijing soil. The preferential absorption and degradation of (−)‐S‐tetraconzole resulted in an enrichment of the (+)‐R‐tetraconazole residue in plant samples, whereas the (+)‐R‐tetraconazole showed a faster degradation in Beijing soil and the stereoselectivity might be caused by microorganisms. No stereoselective degradation was observed in Heilongjiang soil. Chirality 2012. 2012 © Wiley Periodicals, Inc.
Hydrothermal Carbonization: 2. Kinetics of Draff Conversion
Authors: Kruse Andrea , Badoux François , Grandl Robert , Wüst Dominik
Published: January 2012

Die hydrothermale Karbonisierung ist ein vielversprechendes Verfahren, um kohlenstoffreiche Produkte für vielfältige Anwendungen, z. B. als Ersatz für fossile Kohle in Kraftwerken, herzustellen. Die Abnahme des Sauerstoffgehaltes als wesentliches Kriterium für die fortschreitende Karbonisierung wurde am Beispiel von Biertreber als Ausgangstoff untersucht und mit zwei einfachen kinetischen Ansätzen beschrieben. Dabei konnte aufgrund der Zusammensetzung des Produktes zwischen der Karbonisierung durch Kohlendioxid‐ bzw. Wasser‐Abspaltung unterschieden werden.
Spray Drying of BSA‐ and Interferon‐β Loaded Chitosan Particles
Authors: Gruber‐Traub Carmen , Burger‐Kentischer  Anke , Gretzinger Sarah , Hirth Thomas , Weber Achim
Published: January 2012

Die Formulierung und orale Applikation von therapeutischen Peptiden und Proteinen stellt aufgrund des proteolytischen Abbaus im Gastrointestinaltrakt und der geringen Resorption im Darmlumen eine Herausforderung dar. Für eine mögliche orale Verabreichung wurde eine chitosan‐basierte partikuläre Formulierung von Interferon‐β‐1b unter Einsatz eines Sprühtrockungsverfahrens entwickelt. Die Quantifizierung der biologischen Aktivität erfolgte mittels eines Antiviralen‐Assays und eines ELISA‐Assays. Der Aktivitätstest zeigte den Erhalt der biologischen Aktivität des Interferons nach dem Herstellungsprozess.
Adaptive Performance: A New Scale to Measure Individual Performance in Organizations
Authors: Charbonnier‐Voirin Audrey , Roussel Patrice
Published: January 2012

As a component of overall employee performance, adaptive performance refers to the ability of an individual to change his or her behaviour to meet the demands of a new environment. The concept is relevant to firms that face especially complex and volatile business conditions. Research and practice have been hampered by a general lack of a widely available, psychometrically sound, multidimensional scale of adaptive performance that is applicable across a wide range of job contexts. Using both qualitative and quantitative methods, we develop and evaluate a 19‐item scale measuring five dimensions of adaptive performance. Copyright © 2012 ASAC. Published by John Wiley & Sons, Ltd.
Statins Reduce Short‐ and Long‐Term Mortality Associated With Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting: Impact of Postoperative Atrial Fibrillation and Statin Therapy on Survival
Authors: Girerd Nicolas , Pibarot Philippe , Daleau Pascal , Voisine Pierre , O'Hara Gilles , Després Jean‐Pierre , Mathieu Patrick
Published: January 2012

Background:

Postoperative atrial fibrillation (POAF) is a frequent complication of coronary artery bypass grafting (CABG) surgery. The objective of this study was to determine the impact of POAF on both short‐ and long‐term mortality following isolated CABG.

Hypothesis:

POAF is associated with a poorer short and long‐term mortality following CABG.

Methods:

We retrospectively analyzed the preoperative and operative data of 6728 consecutive patients undergoing a first isolated CABG.

Results:

The incidence of POAF was 27.8%. Operative mortality was higher in patients with POAF compared to those without POAF (2.3% vs 0.9%, P < 0.001). On multivariate analysis, POAF remained an independent predictor of operative mortality (odds ratio [OR]: 1.78, P = 0.01). Patients with POAF also had reduced long‐term survival (6‐year survival: 85.3% vs 89.2%, P < 0.001). After adjusting for other predictors of mortality, POAF was significantly associated with increased long‐term mortality (hazard ratio [HR]: 1.35, P = 0.04). Of note, after adjustment for potential confounders, statin treatment had a highly protective effect in POAF patients for both operative mortality (OR: 0.38, P = 0.003) and long‐term mortality (HR: 0.62, P = 0.03), whereas it had no significant effect in patients without POAF.

Conclusions:

POAF is an independent predictor of both short‐ and long‐term mortality following CABG. Moreover, statin therapy was independently associated with better survival in patients with POAF.

Dr. Pibarot holds the Canada Research Chair in Valvular Heart Diseases, Canadian Institutes of Health Research. Dr. Mathieu is a research scholar from the Fonds de Recherches en Santé du Québec, Montreal, Canada. Dr. Després has served as a speaker for Abbott Laboratories, AstraZeneca, Solvay Pharma, GlaxoSmithKline, and Pfizer Canada Inc.; has received research funding from Eli Lilly Canada; and has served on the advisory boards of Novartis, Theratechnologies, Torrent Pharmaceuticals Ltd., and Sanofi‐Aventis. The authors have no other funding, financial relationships, or conflicts of interest to disclose.
Safety of Dental Extractions in Coronary Drug‐Eluting Stenting Patients Without Stopping Multiple Antiplatelet Agents
Authors: Park Mahn‐Won , Her Sung‐Ho , Kwon Jong Bum , Lee Jae Beom , Choi Min‐Seok , Cho Jung Sun , Kim Dong‐Bin , Chung Wook‐Sung , Seung Ki‐Bae , Kim Keon‐Yeop
Published: January 2012

Background:

The risk of excessive bleeding prompts physicians to stop multiple antiplatelet agents before minor surgery, which puts coronary stenting patients at risk for adverse thrombotic events.

Hypothesis:

We hypothesized that most dental extractions can be carried out safely without stopping multiple antiplatelet agents.

Methods:

All dental extraction patients who had undergone coronary stenting and who were also on oral multiple antiplatelet agents therapy were enrolled. One hundred patients underwent dental procedures without stopping antiplatelet agents. All wounds were sutured and followed up at 24 hours, 1 week, and 1 month after the procedure. There were 2233 patients who had not taken oral antiplatelet agents from a health promotion center and had teeth extracted by the same method. After performing propensity‐score matching for the entire population, a total of 100 matched pairs of patients were created. The primary outcome was a composite of excessive intraextraction blood loss, transfusion, and rehospitalization for bleeding, and the secondary outcome was a composite of death, nonfatal myocardial infarction, target lesion revascularization, and stent thrombosis within 1 month after the procedure.

Results:

There were 2 excessive intraextraction bleeding cases that continued at the extraction site for 4 and 5 hours, respectively, in the coronary stenting patients, and 1 excessive intraextraction bleeding case that continued for 3 hours in the control patients. There were no cases of transfusion, rehospitalization for bleeding, or major cardiovascular events for the 2 propensity‐matched groups.

Conclusions:

We found that most dental extractions in coronary stenting patients can be carried out safely without stopping multiple antiplatelet agents.

The authors have no conflicts of interest to disclose.

This study was supported in part by a grant from Yuhan Corporation, Ltd., Seoul, The Republic of Korea.
Protease activation and the signal transduction pathway regulating motility in sperm from the water strider Aquarius remigis
Authors: Miyata Haruhiko , Thaler Catherine D. , Haimo Leah T. , Cardullo Richard A.
Published: January 2012

Many motile processes are regulated such that movement occurs only upon activation of a signaling cascade. Sperm from a variety of species are initially quiescent and must be activated prior to beating. The signaling events leading to the activation and regulation of sperm motility are not well characterized. Mature seminal vesicle sperm from the water strider Aquarius remigis are immotile in vitro, but vigorous motility is activated by trypsin. Trypsin‐activated motility was blocked by pretreatment of the sperm with BAPTA‐AM to chelate intracellular Ca2+ and was partially rescued by subsequent addition of A23187 and Ca2+. Thapsigargin stimulated motility in the absence of trypsin, suggesting that intracellular Ca2+ stores are available. In addition, motility could be fully activated by the phosphatase inhibitor calyculin A, suggesting that the immotile state is maintained by an endogenous phosphatase and that kinase activity is required for motility. The MEK1/2 inhibitor U0126 significantly reduced trypsin activated motility, and MPM‐2, an antibody which recognizes proline‐directed phosphorylation by kinases such as MAPK, recognized components of the water strider sperm flagellum. Antibodies specific for the mouse protease activated receptor PAR2 recognized an antigen on the sperm flagellum. These results suggest that trypsin stimulates a Ca2+ and MAPK mediated signaling pathway and potentially implicate a PAR2‐like protein in regulating motility. © 2012 Wiley Periodicals, Inc.
Preliminary Study of the Anticancer Applications of Mesoporous Materials Functionalized with the Natural Product Betulinic Acid
Authors: Sánchez‐Muñoz Sergio , Gómez‐Ruiz Santiago , Pérez‐Quintanilla Damián , Morante‐Zarcero Sonia , Sierra Isabel , Prashar Sanjiv , Paschke Reinhard , Kaluđerović Goran N.
Published: January 2012

Dehydrated MCM‐41 (S 1) was functionalized under nitrogen with 3‐chloropropyltriethoxysilane (CPTS) and 3‐aminopropyltriethoxysilane (APTS) by grafting in toluene at 80 °C over 48 h to give the corresponding materials S 2 and S 3, respectively. Subsequently, S 2 and S 3 were suspended in methanol and reacted in a nitrogen atmosphere with betulinic acid (BA) for 48 h at 65 °C (in the presence of the triethylamine of S 2) to give the BA‐functionalized materials S 4 and S 5. All materials studied were characterized by powder X‐ray diffraction, X‐ray fluorescence, nitrogen gas sorption, multinuclear MAS NMR spectroscopy, thermogravimetry, UV spectroscopy, IR, SEM, and TEM. To study the release of BA, S 4 and S 5 were suspended in solutions simulating various body pH conditions (pH 7.4, 5.5, and 3.0). Results of the quantification of BA release by HPLC for S 4 show a pH‐dependent and very slow BA release following a logarithmic tendency, while S 5 behaves differently, also pH‐dependent but, in this case, fast release of BA which requires only days for total release of the therapeutic compound. In addition, the cytotoxic activity of all synthesized materials against various cancer cell lines was studied. The results show the absence of an antiproliferative effect on the surfaces without BA S 1–S 3, while an antiproliferative effect was observed with S 4 and S 5 and was attributed to the release of BA in the medium.
Anatomical basis of sun compass navigation I: The general layout of the monarch butterfly brain
Authors: Heinze Stanley , Reppert Steven M.
Published: January 2012

Each fall, eastern North American monarch butterflies (Danaus plexippus) use a time‐compensated sun compass to migrate to their overwintering grounds in central Mexico. The sun compass mechanism involves the neural integration of skylight cues with timing information from circadian clocks to maintain a constant heading. The neuronal substrates for the necessary interactions between compass neurons in the central complex, a prominent structure of the central brain, and circadian clocks are largely unknown. To begin to unravel these neural substrates, we performed 3D reconstructions of all neuropils of the monarch brain based on anti‐synapsin labeling. Our work characterizes 21 well‐defined neuropils (19 paired, 2 unpaired), as well as all synaptic regions between the more classically defined neuropils. We also studied the internal organization of all major neuropils on brain sections, using immunocytochemical stainings against synapsin, serotonin, and γ‐aminobutyric acid. Special emphasis was placed on describing the neuroarchitecture of sun‐compass‐related brain regions and outlining their homologies to other migratory species. In addition to finding many general anatomical similarities to other insects, interspecies comparison also revealed several features that appear unique to the monarch brain. These distinctive features were especially apparent in the visual system and the mushroom body. Overall, we provide a comprehensive analysis of the brain anatomy of the monarch butterfly that will ultimately aid our understanding of the neuronal processes governing animal migration. J. Comp. Neurol. 520:1599–1628, 2012. © 2012 Wiley Periodicals, Inc.
Coherent Motion Reveals Non‐Ergodic Nature of Internal Conversion between Excited States
Authors: Kuhlman Thomas S. , Sølling Theis I. , Møller Klaus B.
Published: January 2012

We found that specific nuclear motion along low‐frequency modes is effective in coupling electronic states and that this motion prevail in some small molecules. Thus, in direct contradiction to what is expected based on the standard models, the internal conversion process can proceed faster for smaller molecules. Specifically, we focus on the S2→S1 internal conversion in cyclobutanone, cyclopentanone, and cyclohexanone. By means of time‐resolved mass spectrometry and photoelectron spectroscopy the relative rate of this transition is determined to be 13:2:1. Remarkably, we observe coherent nuclear motion on the S2 surface in a ring‐puckering mode and motion along this mode in combination with symmetry considerations allow for a consistent explanation of the observed relative time‐scales not afforded by only considering the density of vibrational states or other aspects of the standard models.
DNA “Nanolamps”: “Clicked” DNA Conjugates with Photon Upconverting Nanoparticles as Highly Emissive Biomaterial
Authors: Rubner Moritz M. , Achatz Daniela E. , Mader Heike S. , Stolwijk Judith A. , Wegener Joachim , Harms Gregory S. , Wolfbeis Otto S. , Wagenknecht Hans‐Achim
Published: January 2012

Upconverting nanoparticles (UCNPs) are a highly attractive tool owing to their unique property of showing visible luminescence when excited in the near‐infrared (NIR) region. Plain UCNPs have no biorecognition capabilities, but functionalization of their surface with azido groups renders them conjugatable to ethynyl‐modified oligonucleotides in a bioorthogonal fashion. Single‐stranded DNA was covalently attached to the surface of UCNPs by click chemistry and purified by size exclusion chromatography (SEC) at elevated temperature. Covalent attachment was evidenced by diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy. DNA conjugation makes the particle soluble in water and enables it to recognize its counter strand. Such UCNPs are capable of nonspecifically crossing cell membranes. Confocal microscopy reveals the high potential of the bright UCNPs for live cell imaging in the NIR, where the UCNP–DNA conjugates can be considered to act as a kind of nano‐sized lamp. Furthermore, cross‐linking of those DNA nanolamps yields highly emissive aggregates.
Multiparametric cytometry for exploration of complex cellular dynamics
Authors: Gondois‐Rey Françoise , Granjeaud Samuel , Kieu Suong Le Thi , Herrera Diana , Hirsch Ivan , Olive Daniel
Published: January 2012

The development of polychromatic cytometry has contributed to significant progress in the field of human immunology. Although numerous functional studies of rare cell populations have been performed using this technology, here we used polychromatic cytometry to explore the dynamics of complex cellular systems implicated in innate immunity. We used PBMC stimulated with live influenza virus as an experimental model. We studied the time course of activation of PBMC, which contain DC, monocytes, and NK cells, all of which are, in addition to their innate immune properties, susceptible to Flu infection. We developed 12 color panels to investigate intracellular expression of IFN‐α, TNF‐α, IL‐12, IL‐6, IFN‐γ, CD107, and influenza virus nucleoprotein simultaneously in these cell populations. These panels allowed reproducible determination of activation markers induced in DC after their direct exposure to various stimulations or in NK cells by indirect DC‐mediated activation within the complex cellular environment. The ability to use a low number of cells and reduced quantities of reagents permitted us to perform kinetic experiments. The power of polychromatic cytometry associated with bioinformatic tools allowed us to analyze the multiple functional data generated as dynamic clustering maps. These maps present a readily understandable view of activation events induced in different populations of PBMC. In addition, it reveals new information on the coordination of the complex pathways induced and on the cellular interactions that sustained indirect DC‐mediated NK cell activation. Our work shows that polychromatic cytometry is a tool for discoveries in unexplored complex cell systems, at the crossroads of immunology and virology. © 2012 International Society for Advancement of Cytometry
FCS 3.1 Implementation Guidance
Authors: Bray Chris , Spidlen Josef , Brinkman Ryan R.
Published: January 2012

The Flow Cytometry Standard (FCS) format was developed back in 1984. Since then, FCS became the standard file format supported by all flow cytometry software and hardware vendors. Over the years, updates were incorporated to adapt to technological advancements in both flow cytometry and computing technologies. However, flexibility in how data may be stored in FCS has led to implementation difficulties for instrument vendors and third party software developers. In this technical note, we are providing implementation guidance and examples related to FCS 3.1, the latest version of the standard. By publishing this text, we intend to prevent potential compatibility issues that could be faced when implementing the FCS spillover and preferred display keywords that have arisen during discussions among some implementers. © 2012 International Society for Advancement of Cytometry.
Peculiarities of Vibrational Spectra and Electronic Structure of the Five‐Membered Metallacyclocumulenes of the Group 4 Metals
Authors: Aysin Rinat R. , Leites Larissa A. , Burlakov Vladimir V. , Shur Vladimir B. , Beweries Torsten , Rosenthal Uwe
Published: January 2012

The vibrational (Raman and IR) spectra of metallacyclic cumulenes of the type Cp2M(η4‐tBuC4tBu) [M = Ti (1), Zr (2), Hf (3)] were obtained and analyzed in terms of normal coordinate calculations. The system of three cumulated C=C bonds in the five‐membered metallacycle was shown to exhibit a peculiar spectral pattern with three normal modes with frequencies at ca. 1900 (νs1), 1650 (νas2), and 1280 cm–1 (νs3). The νs1 mode is a symmetric stretch of the two equivalent C1–C2 and C3–C4 bonds (with simultaneous contraction of the central C2–C3 bond), the νas2 mode is their antisymmetric combination, while the νs3 mode has a complex eigenvector and involves a “breathing” motion of the metallacycle as a whole along with C–CtBu bond stretches. Reconstruction of the electron‐density distribution in the molecules studied by using Bader's AIM theory resulted in a specific molecular graph of the metallacycle, that with the so‐called “T‐shaped” configuration, pointing to topological instability of the system. This is in contrast to analogously calculated “normal” bonding patterns for related cyclopropene complexes Cp2Ti(η2‐RC2R).
N1‐Functionalized Indole‐Phosphane Oxazoline (IndPHOX) Ligands in Asymmetric Allylic Substitution Reactions
Authors: Wang Yu , Vaismaa Matti J. P. , Rissanen Kari , Franzén Robert
Published: January 2012

N‐Functionalized IndPHOX ligands bearing various groups have been synthesized and the effects of the N1‐substituent on the reaction rate, yield, and asymmetric induction in a palladium‐catalyzed allylic substitution reaction are reported. The presence of an oxygen atom in the ligands, namely an N‐MOM or N‐THP group, led to enhancement of the enantioselectivity in the allylic amination reaction. In addition, a ligand with a chiral oxazoline ring at C‐1 and a phosphane substituent at C‐2 provided high enantioselectivity in good yield in an asymmetric allylic alkylation reaction.
Breaking apart the typical mortality salience manipulation: Two questions, two outcomes
Authors: Burgin Chris J. , Sanders Matthew A. , vanDellen Michelle R. , Martin Leonard L.
Published: January 2012

The typical mortality salience manipulation asks participants to reflect on two questions, one about the emotions associated with the thought of death and the other about what happens after one dies. In five experiments, we separated these two questions and gave participants either one or a control question. In Experiment 1, participants' responses to the afterlife question were coded as being informed more by cultural knowledge and values compared with responses to the emotion question. Experiments 2 and 3 demonstrated that participants responding to the afterlife question showed greater stereotype usage compared with those responding to the emotion or a control question. In Experiment 4, results illustrate that the afterlife and emotion question differ on various coding dimensions related to self‐focus, emotion, and culturally related death words, but not death‐related words. In addition, participants who responded to the afterlife question demonstrated greater cultural worldview defense by setting a higher bail for an alleged prostitute compared with those who answered the emotion or a control question. In Experiment 5, participants responding to the emotion question demonstrated a greater preference for personally endorsed values compared with those who responded to the emotion or a control question. These results suggest that the two questions used in the common mortality salience manipulation produce different results when separated. Copyright © 2012 John Wiley & Sons, Ltd.
Comparative effects of the herbicides chlortoluron and mesotrione on freshwater microalgae
Authors: Valiente Moro Claire , Bricheux Genevieve , Portelli Christophe , Bohatier Jacques
Published: January 2012

Extensive use of herbicides in agriculture is accompanied by the risk of environmental contamination of aquatic ecosystems. The present study shows the effects of the herbicides chlortoluron and mesotrione on three microalgae species: two chlorophyceae (Pediastrum tetras, Ankistrodesmus fusiformis) and one diatom (Amphora coffeaeformis). The authors calculated the IC50 for one chlorophyceae and the diatom. The order of toxicity (median inhibitory concentration [IC50]) for mesotrione was A. coffeaeformis (13.1 mg/L) > A. fusiformis (56.1 mg/L) and A. fusiformis (0.05 mg/L) > A. coffeaeformis (0.08 mg/L) for chlortoluron. The impact of herbicides applied at 0.2 mg/L was then examined in Erlenmeyer flasks by monitoring for growth, pigment content, and metabolic activity. Algal responses varied widely according to species and herbicide. For example, chlortoluron showed a significant inhibitory effect on the growth of A. coffeaeformis, whereas mesotrione induced an increase in cellular density in A. fusiformis. Other cellular parameters, such as pigment content in P. tetras, were stimulated by both herbicides. The results obtained confirmed that microalgae cultures are clearly affected by acute and chronic exposition to herbicides. Further monitoring should be carried out in the field to assess the impact of sublethal levels of toxicity and the growth-enhancing effects of mesotrione and chlortoluron on natural algae communities. Environ. Toxicol. Chem. 2012;31:778–786. © 2012 SETAC
Ameliorative effects of sodium chloride on acute copper toxicity among Cope's gray tree frog (Hyla chrysoscelis) and green frog (Rana clamitans) embryos
Authors: Brown Maria G. , Dobbs Emily K. , Snodgrass Joel W. , Ownby David R.
Published: January 2012

Urban stormwater runoff is composed of a mixture of components, including polycyclic aromatic hydrocarbons, metals, deicing agents, and many others. The fate of these chemicals is often in stormwater detention ponds that are used by amphibians for breeding. Among aquatic organisms, the toxic mechanism for many metals involves interference with active Na+ and Cl− uptake. Addition of cations has been shown to reduce the toxicity of metals among some aquatic organisms through competitive inhibition, but no studies have investigated the interaction between NaCl and Cu among amphibian embryos and larvae. To determine the degree to which NaCl may ameliorate the toxicity of Cu to amphibian embryos and larvae, the authors exposed Hyla chrysoscelis (Cope's gray treefrogs) and Rana (Lithobates) clamitans (green frogs) to seven levels of Cu and NaCl in fully factorial experiments. When exposure was in artificial hard water, Cu was highly toxic to both species (96-h median lethal concentration [LC50] of 44.7 µg/L and 162.6 µg/L for H. chrysoscelis and R. clamitans, respectively). However, approximately 500 mg/L of NaCl eliminated Cu toxicity over the range of Cu concentrations used in the experiments (maximum 150 µg Cu/L for H. chrysoscelis and 325 µg Cu/L for R. clamitans). The current results suggest that NaCl is likely responsible for the toxic effects of NaCl and metal mixtures that might be typical of runoff from road surfaces in northern latitudes. Environ. Toxicol. Chem. 2012;31:836–842. © 2012 SETAC
Effects of progesterone on reproduction and embryonic development in the fathead minnow (Pimephales promelas)
Authors: DeQuattro Zachary A. , Peissig Evan J. , Antkiewicz Dagmara S. , Lundgren Erica J. , Hedman Curtis J. , Hemming Jocelyn D.C. , Barry Terence P.
Published: January 2012

High concentrations (375 ng/L) of the steroid hormone progesterone (P4) were measured in snowmelt runoff associated with large livestock-feeding operations in Wisconsin. To gain insight into the potential endocrine-disrupting effects of P4 in fish, experiments were conducted to evaluate the effects of short-term exposure to environmentally relevant concentrations of P4 on reproduction and embryonic development in the fathead minnow (Pimephales promelas). For the reproduction assay, groups of reproductively mature fish were exposed for 21 d to nominal concentrations of 0, 10, 100, and 1,000 ng/L P4 in a flow-through system, and various key reproductive endpoints (e.g., egg number, fertilization success) were quantified throughout the exposure period. The embryonic development assay consisted of incubating fathead minnow eggs in static culture to quantify the effects of P4 on early development and hatching success. Progesterone caused dose-dependent decreases in fecundity and fertility and significantly reduced gonadosomatic index and vitellogenin gene expression in females. There were no effects of P4 on early embryonic development or hatching success. Progesterone may be a significant endocrine-disrupting chemical in fish. Environ. Toxicol. Chem. 2012;31:851–856. © 2012 SETAC
Bioaccumulation of waterborne Ni in Dreissena polymorpha: A stable isotope experiment to assess the effect of zinc, calcium, and dissolved organic matter
Authors: Bourgeault A. , Gourlay-Francé C. , Ayrault S. , Tusseau-Vuillemin M.-H.
Published: January 2012

The effect of Ca, Zn, and dissolved natural organic matter (NOM) on waterborne Ni accumulation was investigated in a freshwater mussel. An enriched stable metal isotope tracer was required to measure the Ni uptake rate accurately. Zebra mussels were exposed to environmentally relevant concentrations of 62Ni (from 0.5 to 8 µg/L) for 48 h in media spiked with Ca, Zn, or dissolved NOM. The 62Ni uptake was inhibited by Ca (from 0.138 ± 0.021 to 0.061 ± 0.010 L/g/d for Ca concentrations ranging from 43 to 133 mg/L) and enhanced by Zn (from 0.051 ± 0.006 to 0.109 ± 0.007 L/g/d for Zn concentrations ranging from 6.6 to 38.3 µg/L). The mechanisms behind the synergistic effect of Zn remain unclear, yet it can be hypothesized that Ni uptake is facilitated by Zn-dependent transport sites. To formalize the effects of Ca and Zn, a model was proposed to express the Ni uptake rate as a function of the mussels' filtration rate and of Ca and Zn concentrations. The 62Ni uptake increased at low NOM concentrations and decreased at higher concentrations. This could be explained by the influence of NOM on both the speciation of Ni and the filtration activity of mussels. At high NOM concentrations, a modification of the membrane's permeability might also have favored Ni uptake, although this was not clearly established in this study. Therefore, the effect of water composition on Ni bioavailability to zebra mussels cannot be predicted by competition and complexation models alone, because it also influences the animal's physiology. Environ. Toxicol. Chem. 2012;31:819–827. © 2012 SETAC
Tissue distribution of perfluorinated compounds in farmed freshwater fish and human exposure by consumption
Authors: Shi Yali , Wang Jieming , Pan Yuanyuan , Cai Yaqi
Published: January 2012

In the present study, the levels of 14 perfluorinated compounds (PFCs) were analyzed in the blood, liver, muscle, brain, and eggs of popular farmed freshwater fish from Beijing. Perfluorooctane sulfonate (PFOS) was the predominant compound in all samples, with the highest concentration at 70.7 ng/g wet weight. The highest mean levels of PFOS in all tissues were observed in bighead (1.48–22.5 ng/g wet wt) and the lowest in tilapia (0.260–1.63 ng/g wet wt). In addition, perfluoroundecanoic acid was the second dominant PFC in blood, liver, muscle, and eggs, with the highest concentration at 19.2 ng/g wet weight. However, perfluorodecanoic acid levels (less than the limit of detection [LOD] to 0.963 ng/g wet wt) were similar to or slightly higher than perfluoroundecanoic acid levels (<LOD to 0.918 ng/g wet wt) in the brain. Generally, the highest mean concentrations of PFOS and total PFCs were found in fish blood, followed by liver, brain, and muscle, further supporting the premise that PFOS can bind more easily to serum proteins than to fatty tissues. The egg to liver ratios as maternal transfer ratios were calculated for PFOS, ranging from 0.93 to 2.0. Furthermore, based on consumption information for fish in Beijing, the human dietary intake of PFCs through fish consumption were estimated at 0.24 ng/kg/d for PFOS and 0.44 ng/kg/d for total PFC. These results indicate a low health risk posed from PFCs to the residents of Beijing through the consumption of fish. Environ. Toxicol. Chem. 2012;31:717–723. © 2012 SETAC
Performance of magnetic resonance elastography and diffusion-weighted imaging for the staging of hepatic fibrosis: A meta-analysis
Authors: Wang Qing-Bing , Zhu Hui , Liu Hai-Ling , Zhang Bei
Published: January 2012

A meta-analysis was performed to assess and compare the accuracies of magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI) for the staging of hepatic fibrosis. Online journal databases and a manual search from January 2000 to May 2011 were used. We identified 41 studies, but only 14 met the criteria to perform a meta-analysis assessing MRE (five trials) or DWI (10 trials). Fibrosis was categorized by redistribution into five stages according to histopathological description. A bivariate binomial model was used to combine the sensitivity and specificity and their 95% confidence intervals (CIs), from which diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and summary receiver operating characteristic (sROC) were derived to indicate the diagnostic accuracy of imaging modalities. With MRE, the sensitivity, specificity, DOR, PLR, NLR, and area under sROC curve (with 95% CIs) for staging F0 ˜ F1 versus F2 ˜ F4 and F0 ˜ F2 versus F3 ˜ F4 were 0.94 (0.81-0.98), 0.95 (0.87-0.98), 20 (7-57), 0.06 (0.02-0.22), 317 (55-1,796), 0.98 (0.97-0.99) and 0.92 (0.85-0.96), 0.96 (0.91-0.98), 21 (10-45), 0.08 (0.04-0.16), 251 (103-609), and 0.98 (0.96-0.99), respectively; and with DWI, these values were 0.77 (0.71-0.82), 0.78 (0.69-0.85), 3 (2-5), 0.30 (0.22-0.40), 12 (6-21), 0.83 (0.79-0.86) and 0.72 (0.60-0.81), 0.84 (0.77-0.89), 5 (3-7), 0.34 (0.23-0.50), 13 (6-29), and 0.86 (0.83-0.89), respectively. A z test demonstrated that MRE had a significantly higher accuracy than DWI in those indicators (P < 0.05). Conclusion: MRE is more reliable for staging hepatic fibrosis, compared with DWI, with a high combination of sensitivity, specificity, likelihood ratios, DOR, and area under sROC curve. (HEPATOLOGY 2012;56:239–247)
Cidea promotes hepatic steatosis by sensing dietary fatty acids
Authors: Zhou Linkang , Xu Li , Ye Jing , Li De , Wang Wenshan , Li Xuanhe , Wu Lizhen , Wang Hui , Guan Feifei , Li Peng
Published: January 2012

High levels of dietary saturated fat have been closely associated with the development of hepatic steatosis, but the factors that mediate this process remain elusive. Here, we observed that the level of cell death-inducing DNA fragmentation factor-alpha-like effector a (Cidea) expression was highly correlated with the severity of hepatic steatosis in humans. Overexpression of Cidea in mouse liver resulted in increased hepatic lipid accumulation and the formation of large lipid droplets (LDs). In contrast, mice with a Cidea deficiency had decreased lipid accumulation and alleviated hepatic steatosis when they received a high-fat-diet feeding or in ob/ob mice. Furthermore, the knockdown of Cidea in livers of ob/ob mice resulted in significantly reduced hepatic lipid accumulation and smaller LDs. Importantly, we observed that Cidea expression in hepatocytes was specifically induced by saturated fatty acids (FAs), and such induction was reduced when sterol response element-binding protein (SREBP)1c was knocked down. In contrast, the overexpression of SREBP1c restored the saturated FA-induced expression of Cidea. In addition, we observed that the stability of Cidea protein in hepatocytes increased significantly in response to treatment with FAs. Conclusion: Cidea plays critical roles in promoting hepatic lipid accumulation and in the development of hepatic steatosis by acting as a sensor that responds to diets that contain FAs. (Hepatology 2012;56:95–107)
Inhibition of hepcidin transcription by growth factors
Authors: Goodnough Julia B. , Ramos Emilio , Nemeth Elizabeta , Ganz Tomas
Published: January 2012

The hepatic peptide hormone hepcidin controls the duodenal absorption of iron, its storage, and its systemic distribution. Hepcidin production is often insufficient in chronic hepatitis C and alcoholic liver disease, leading to hyperabsorption of iron and its accumulation in the liver. Hepatocyte growth factor (HGF) and epidermal growth factor (EGF) mediate hepatic regeneration after liver injury. We examined the effect of these growth factors on hepcidin synthesis by hepatocytes. HGF and EGF treatment of primary mouse hepatocytes, as well as EGF administration in mice, suppressed hepcidin messenger RNA (mRNA) synthesis. The suppression of hepcidin by these growth factors was transcriptional, and was mediated by a direct effect of HGF and EGF on the bone morphogenetic protein (BMP) pathway regulating hepcidin synthesis. We further show that growth factors interfered with nuclear localization of activated sons of mothers against decapentaplegic (Smad) and increased the nuclear pool of the BMP transcriptional corepressor TG-interacting factor (TGIF). In a kinase screen with small-molecule kinase inhibitors, inhibitors in the PI3 kinase pathway and in the mitogen-activated ERK kinase/extracellular signal-regulated kinase (MEK/ERK) pathway prevented HGF suppression of hepcidin in primary mouse hepatocytes. Conclusion: HGF and EGF suppress hepatic hepcidin synthesis, in part through PI3 kinase MEK/ERK kinase pathways which may be modulating the nuclear localization of BMP pathway transcriptional regulators including activated Smads1/5/8 and the corepressor TGIF. EGF, HGF, and possibly other growth factors that activate similar pathways may contribute to hepcidin suppression in chronic liver diseases, promote iron accumulation in the liver, and exacerbate the destructive disease processes. (HEPATOLOGY 2012;56:291–299)