bluuebunny/crossref_metadata_2025 huggingface dataset:
Photoinduced Release of Neurotransmitter Amino Acids from Coumarin‐Fused Julolidine Ester Cages
Authors: Piloto Ana M. , Hungerford Graham , Costa Susana P. G. , Gonçalves M. Sameiro T.
Published: October 2013

The photoinduced release of several neurotransmitter amino acids (glycine, alanine, glutamic acid, β‐alanine and γ‐aminobutyric acid) was accomplished from ester cages based on a new photoremovable protecting group consisting of a coumarin built on the julolidine nucleus, namely a (11‐oxo‐2,3,5,6,7,11‐hexahydro‐1H‐pyrano[2,3‐f]pyrido[3,2,1‐ij]quinolin‐9‐yl)methyl group. Photolysis and steady‐state sensitization studies revealed that release of the active molecule occurred in short irradiation times at long wavelengths, with a very promising performance at 419 nm. Given the interest in the development of novel protecting groups that are cleavable with UV A or even visible radiation, it was found that a structural modification in the coumarin ring by assembly of a fused julolidine leads to a promising photolabile protecting group for organic synthesis and also for bioapplications.
Palladium‐Catalysed Synthesis of 9H‐Pyrrolo[1,2‐a]indol‐9‐ones and the Isomeric Indeno[2,1‐b]pyrrol‐8‐ones
Authors: Wang Shuyang , Yang Qinghua , Dong Jingjing , Li Changwei , Sun Li , Song Chuanjun , Chang Junbiao
Published: October 2013

9H‐Pyrrolo[1,2‐a]indol‐9‐ones and isomeric indeno[2,1‐b]pyrrol‐8‐ones could be obtained in moderate to good isolated yields, by subjecting the same substrates, 2‐bromophenyl N‐tosyl‐2‐pyrrolyl ketones, to different palladium catalysts.
Phosphonate Analogues of Arabinose 5‐Phosphate: Putative Ligands for Arabinose 5‐Phosphate Isomerases
Authors: Gabrielli Luca , Airoldi Cristina , Sperandeo Paola , Gianera Serena , Polissi Alessandra , Nicotra Francesco , Cipolla Laura
Published: October 2013

Metabolically stable arabinose 5‐phosphate analogues possessing phosphate mimetic groups at the 5‐position were synthesized and evaluated by saturation‐transfer‐difference (STD) NMR studies for their ability to interact with arabinose 5‐phosphate isomerase. Isosteric methylphosphonate 1 and (difluoromethyl)phosphonate 3 were recognised and bound by the catalytic pocket of the enzyme. The synthesized compounds were tested in vivo on E. coli and P. aeruginosa strains in order to evaluate their antibacterial activity.
Selective Reduction of Amino Allenephosphonates: Preparation of α‐Amino Vinylphosphonates
Authors: Adler Pauline , Gomes Filipe , Fadel Antoine , Rabasso Nicolas
Published: October 2013

α‐Amino vinylphosphonates were prepared by chemo‐ and stereoselective reduction of α‐amino allenephosphonates. Our results showed that the substituents on the allene, phosphonate, and nitrogen moieties affected the stereoselectivity of the reduction. Z‐α‐Amino vinylphosphonates were prepared with good selectivities up to > 95:5.
An (Aminopyrimidinato)titanium Catalyst for the Hydroamination of Alkynes and Alkenes
Authors: Brahms Christian , Tholen Patrik , Saak Wolfgang , Doye Sven
Published: October 2013

A new (aminopyrimidinato)titanium complex has been synthesised from inexpensive and easily accessible 2‐(tert‐butylamino)pyrimidine and [Ti(NMe2)4] and used as a catalyst for the intermolecular hydroamination of alkynes as well as the cyclization of aminoalkenes. The hydroamination reactions of 1‐phenylpropyne and terminal arylalkynes deliver the corresponding anti‐Markovnikov addition products with excellent yields and regioselectivities.
Perfluoroalkylated Bis(sulfilimine)s and Bis(sulfoximine)s by a Ritter‐Type Reaction
Authors: Pégot Bruce , Urban Céline , Diter Patrick , Magnier Emmanuel
Published: October 2013

Our synthetic methodology, which was previously developed for the preparation of perfluoroalkyl sulfilimines by a reaction between fluorinated sulfoxides and nitriles, has been successfully extended to dinitriles. According to the reaction conditions, we can preferentially produce a cyano monosulfilimine or a bis(sulfilimine). New cyano thioethers have been synthesized through a rearrangement process. Mono‐ and bis(sulfilimine)s were also oxidized to afford the corresponding sulfoximines, which provide a direct route to potential new ligands for catalysis and new electrophilic perfluoroalkylating reagents.
Synthesis of CF3‐Substituted Olefins by Julia–Kocienski Olefination Using 2‐[(2,2,2‐Trifluoroethyl)sulfonyl]benzo[d]thiazole as Trifluoromethylation Agent
Authors: Hafner Andreas , Fischer Tobias S. , Bräse Stefan
Published: October 2013

A modified Julia–Kocienski protocol was investigated for the synthesis of CF3‐substituted terminal olefins. By employing a simple one‐step procedure, aldehydes were converted into the corresponding CF3‐substituted olefins using 2‐[(2,2,2‐trifluoroethyl)sulfonyl]benzo[d]thiazole as the trifluoromethylation agent. This sulfone was prepared on a gram scale in two steps from inexpensive and commercially available trifluoroethanol. The Julia–Kocienski olefination tolerated various functional groups, and the trifluoromethylated olefins were obtained in good yields. However, the E/Z selectivity was strongly substrate dependent, and only moderate selectivities could be achieved.
Synthesis, Antiviral Evaluation, and Computational Studies of Cyclobutane and Cyclobutene L‐Nucleoside Analogues
Authors: Miralles‐Llumà Rosa , Figueras Antoni , Busqué Félix , Alvarez‐Larena Angel , Balzarini Jan , Figueredo Marta , Font Josep , Alibés Ramon , Maréchal Jean‐Didier
Published: October 2013

This paper describes the stereoselective synthesis of a series of functionalized cyclobutane and cyclobutene L‐nucleoside analogues featuring a methylene spacer between the carbocycle and the nucleobase. These L‐nucleoside analogues were subjected to comprehensive screening for antiviral activity. To obtain knowledge at the molecular structural level relevant for designing future analogues, the mechanism of action of these L‐nucleoside analogues as anti‐herpes simplex virus agents was investigated by computational approaches. In particular, protein–ligand docking calculations were used to rationalize the ability of the prodrug candidates to be activated. Docking experiments were performed on the three kinases involved in the activation process of thymine and guanine derivatives.
Transition‐Metal‐Free Synthesis of (E)‐Vinyl Sulfones from Vinyl Halides in Water
Authors: Liang Shuai , Zhang Ruo‐Yi , Wang Gao , Chen Shan‐Yong , Yu Xiao‐Qi
Published: October 2013

A practical transition‐metal‐free procedure for the synthesis of (E)‐vinyl sulfones through the coupling of vinyl halides with sodium sulfinates in water is reported. The reaction is strongly influenced by the presence of acids, and the use of nBu4NBr promotes its efficiency.
Iron‐Catalyzed Three‐Component Synthesis of α‐Amino Acid Derivatives
Authors: Halli Juliette , Manolikakes Georg
Published: October 2013

An efficient, iron‐catalyzed, three‐component synthesis of arylglycines starting from readily available amides, glyoxalates, and arenes or heteroarenes has been developed. This method provides a versatile, atom‐economic, and cost‐effective route to arylglycines with water as the only byproduct. With carbamates as the amide component, various synthetically useful N‐protected arylglycine derivatives could be prepared.
Electrochemical Behavior of Gold Nanoparticles Generated In Situ on 3‐(1‐Imidazolyl)propyl‐silsesquioxane
Authors: Simon Ícaro A. , Vacaro Bernardo B. , Nunes Michael R. , Benvenutti Edilson V. , Dias Silvio L. P. , Gushikem Yoshitaka , Arguello Jacqueline
Published: October 2013

Gold nanoparticles of different morphologies have been synthesized on a silica‐based organic‐inorganic hybrid material for catalytic applications. The gold nanoparticles formations proceed through in situ chemical reduction of the AuCl4− anions previously adsorbed on 3‐(1‐imidazolyl)propyl‐silsesquioxane, which plays the role of substrate and stabilizer. Two distinct reducing agents, sodium citrate and sodium borohydride, were employed to generate gold nanoparticles of different sizes. UV‐vis diffuse reflectance as well as transmission electron microscopy were employed to evaluate the particle’s morphology. Modified carbon paste electrodes were prepared from these materials and their electrochemical behavior investigated using potassium ferrocyanide and 4‐nitrophenol as redox model compounds. Both AuNPs‐modified electrodes decreased the overpotential of 4‐nitrophenol reduction by around 90 mV compared to the unmodified electrode as evidenced by cyclic voltammetry experiment. However, the smaller diameter particles (borohydride‐reduced) produced more significant catalytic effect as a consequence of their large surface area. Regarding the sensing parameters, the sensitivity is higher for the borohydride‐reduced AuNPs while the values of limit of detection are of the same order of magnitude. Thus, the detection limit and sensitivity are 70.0±0.6 nM and 187 µA/mM for the citrate‐reduced AuNPs; and 75.0±2.2 nM and 238 µA/mM for the borohydride‐reduced AuNPs.
Simultaneous Adsorptive Cathodic Stripping Voltammetric Determination of Nickel(II) and Cobalt(II) at an In Situ Bismuth‐Modified Gold Electrode
Authors: Mardegan A. , Dal Borgo S. , Scopece P. , Moretto L. M. , Hočevar S. B. , Ugo P.
Published: October 2013

A study on the simultaneous determination of Ni(II) and Co(II) dimethylglyoximates (Ni‐DMG and Co‐DMG) through adsorptive cathodic stripping voltammetry at an in situ bismuth‐modified gold electrode (Bi‐AuE) is reported. The key operational parameters, such as Bi(III) concentration, accumulation potential and accumulation time were optimized and the morphology of the Bi‐microcrystals deposited on the Au‐electrode was studied. The Bi‐AuE allowed convenient analysis of trace concentrations of solely Ni(II) or of Ni(II) and Co(II) together, with cathodic stripping voltammograms characterized by well‐separated stripping peaks. The calculated limit of detection (LOD) was 40 ng L−1 for Ni(II) alone, whereas the LOD was 98 ng L−1 for Ni(II) and 58 ng L−1 for Co(II), when both metal ions were measured together. The optimized method was finally applied to the analysis of certified spring water (NIST1640a) and of natural water sampled in the Lagoon of Venice. The results obtained with the Bi‐AuE were in satisfactory agreement with the certified values and with those provided by complementary techniques, i.e., ICP‐OES and ICP‐MS.
A Facile One‐Step Method for the Synthesis of Reduced Graphene Oxide Nanocomposites by NADH as Reducing Agent and Its Application in NADH Sensing
Authors: Tabrizi Mahmoud Amouzadeh , Zand Zahra
Published: October 2013

Here, we report a green and eco‐friendly approach to synthesize reduced graphene oxide (rGO) via a mild hydrothermal process using nicotinamide adenine dinucleotide (NADH) as a reducing agent. The obtained rGO was characterized by UV‐visible absorption spectroscopy (UV‐vis), X‐ray diffraction spectroscopy, atomic force microscopy (AFM) and scanning electron microscopy (SEM). Electrochemical experiments indicated that the rGO/GC electrode exhibited an excellent electrocatalytic activity towards the oxidation of NADH, which can be attributed to the excellent electrical conductivity and high specific surface area of the rGO composite. The resulting biosensor showed highly sensitive amperometric response to NADH with a low detection limit (0.6 µM).
An optimized method to extract poplar leaf proteins for two‐dimensional gel electrophoresis guided by analysis of polysaccharides and phenolic compounds
Authors: Szuba Agnieszka , Wojakowska Anna , Lorenc–Plucińska Gabriela
Published: October 2013

Commonly used methods for protein extraction from plant leaves, such as extraction with phenol or a combination of trichloroacetic acid and acetone, were ineffective for four tested cultivars of poplar. Moreover, multiple protocols for 2DE of the extracted proteins gave different results when protein profiles of relatively closely related plants were compared. Given that polycyclic compounds strongly hinder 2DE, we analyzed the impact of polyphenols and polysaccharides present in the plant tissues used for protein extraction, on the quality of 2DE protein profiles. Analysis of content of polyphenols and polysaccharides in leaves of poplar cultivars showed that even small differences in concentrations of analyzed metabolites accompany large differences between poplar cultivars when considering the susceptibility of samples to protein extraction for 2DE. High‐quality 2DE results were correlated with decreased amounts of polyphenols. Additional analysis using MS/MS suggested that only levels of total phenolics affected the results of 2DE. Soluble total nonstructural carbohydrates also had a negative effect, but the level of starch was not important. Finally, we present an optimized method for extraction of proteins from poplar leaves, which enables reliable comparative analysis of four different poplar cultivars, that is, “Eridano,” “Villafranca,” “NE‐42,” and “Luisa Avanzo,” which have not yet been used for the proteomic studies.
Point of care creatinine measurement for diagnosis of renal disease using a disposable microchip
Authors: Ávila Mónica , Floris Arjan , Staal Steven , Ríos Ángel , Eijkel Jan , van den Berg Albert
Published: October 2013

A point‐of‐care device for the determination of elevated creatinine levels in blood is reported. This device potentially offers a new and simple clinical regime for the determination of creatinine that will give huge time savings and removal of several steps of determination. The test employs a disposable prefilled microchip and the handheld Medimate Multireader®. By optimizing the analytical conditions it was found that the LOD of the proposed method was 87 μM creatinine, close to the normal human serum levels that are in the range of 60 to 100 μM. A statistical analysis of the residual shows a normal distribution, indicating the absence of systematic errors in the proposed method. The test can be used to distinguish patients with renal insufficiency (creatinine levels >100 μM) from healthy persons. Long‐term monitoring could furthermore distinguish between acute renal failure and chronic kidney disease by the rate of creatinine concentration rise.
The axial rearrangement mixer: Working principles and in‐depth investigation
Authors: Goovaerts Robert , Vandermeersch Tobias , De Beeck Jeff Op , Eghbali Hamed , Desmet Gert
Published: October 2013

In the current paper, an axial rearrangement mixer is studied. The mixer aims to flatten out occasional composition fluctuations originating from the pump. In a first phase, dispersion in a single mixer channel is investigated using pulses introduced by a dedicated injection pulse generator. The mixing in the single channel is studied for different flow rates and a model is presented based on the experimental data. Next, the resulting signal for the whole mixer is studied.
Sensitive determination of positional isomers of benzenediols in human urine by boronate affinity capillary electrophoresis with chemiluminescence detection
Authors: Lin Zian , Sun Xiaobo , Hu Wenli , Yin Yuqing , Chen Guonan
Published: October 2013

A boronate ACE coupled with chemiluminescence (CL) detection was developed for sensitive determination of three isomeric benzenediols, which was based on the principle of an inhibited effect of borate complexation on the CL reaction between luminol and potassium hexacyanoferrate (K3Fe(CN)6) in alkaline solution. The effects of some important factors on CE separation and CL intensity were systemically investigated. Baseline separation of isomeric benzenediols including o‐benzenediol, m‐benzenediol, and p‐benzenediol was achieved by using a mobile phase of 40 mmol/L glycine–NaOH buffer at pH 9.4 containing 0.8 mmol/L luminol and 0.4 mol/L 4‐iodophenylboronic acid. The calibration curves of the analytes by plotting the peak height against corresponding concentration were linear over the range of 4.5 × 10−8 ∼ 4.5 × 10−5 mol/L for p‐benzenediol, 6.8 × 10−8 ∼ 2.7 × 10−5 mol/L for m‐benzenediol, and 9.0 × 10−8 ∼ 4.5 × 10−5 mol/L for o‐benzenediol. The corresponding detection limits for p‐, m‐, and o‐benzenediols were 2.8 × 10−8 mol/L (68 amol), 3.2 × 10−8 mol/L (108.4 amol), and 3.7 × 10−8 mol/L (125.8 amol; S/N = 3), respectively. The proposed method has been successfully applied to the analysis of trace benzenediols in spiked human urine sample and the recoveries were >97.2%. Our primary result demonstrated the proposed CE‐CL method has great potential for biomarker determination in clinical diagnosis.
Very fast electrophoretic determination of creatinine and uric acid in human urine using a combination of two capillaries with different internal diameters
Authors: Pavlíček Václav , Tůma Petr , Matějčková Jana , Samcová Eva
Published: October 2013

A capillary system formed by combining 25 and 100 μm id capillaries was used in the short‐end injection mode to determine creatinine and uric acid in human urine. The separation was performed at an electric field intensity of 2.3 kV/cm. Creatinine was determined in a BGE with a composition of 20 mM citric acid/NaOH (pH 3.0), and uric acid was determined in 20 mM MES/NaOH (pH 6.0). Under these conditions, migration times of 12.2 s for creatinine and 8.6 s for uric acid were achieved. The LOD value is 2.4 mg/L for creatinine and 0.9 mg/L for uric acid; the RSD for the migration time varies in the range 0.7–1.1% (intra day) to 1.0–7.5% (inter day); RSDs for the peak areas equalled 3.4–4.0% (intra day) and 4.3–4.7% (inter day). The determined creatinine values in seven urine samples vary in the range 221–1394 mg/L for creatinine and 87–615 mg/L for uric acid. t‐Test did not reveal any statistically significant difference between the developed CE methodologies and reference methods – Jaffé reaction for creatinine and enzymatic uricase test for uric acid.
Evaluation of electroosmotic markers in aqueous and nonaqueous capillary electrophoresis
Authors: Hellqvist Alexander , Hedeland Ylva , Pettersson Curt
Published: October 2013

The most common method to determine the EOF in CE is to measure the migration time for a neutral marker. In this study, 12 compounds (three novel and some previously used) were investigated as EOF markers in aqueous and nonaqueous BGEs. In the aqueous buffer systems (ammonium acetate, sodium phosphate, and sodium borate) the evaluation included a wide pH range (2–12). Two BGEs contained chiral selectors (sulphated‐β‐CD, (−)‐diketogulonic acid) and one that contained a micellar agent (SDS) were included in the study. The majority of the evaluated compounds were found to migrate with the EOF in the water‐based BGEs and are thus useful as EOF markers. However, in the SDS‐based BGE only four of the compounds (acetone, acrylamide, DMSO, and ethanol) were found to be applicable. In the nonaqueous BGEs 11 markers (acetone, acetophenone, acrylamide, anthracene, benzene, 4‐(4‐methoxybenzylamino)‐7‐nitro‐2,1,3‐benzoxadiazole, benzyl alcohol, 2,5‐diphenyloxazole, ethanol, flavone, and mesityl oxide) seemed to be functional as EOF markers. Even though several of the evaluated compounds can be used as EOF markers in the investigated BGEs, the authors would recommend the use of acrylamide as a general marker for UV detection. Furthermore, the four fluorescent markers (of which three were novel) gave RSD values equal to the other markers and can be used for the determination of the EOF in CE or microchip CE with fluorescence detection.
Advance of CE and CEC in phytochemical analysis (2012–2013)
Authors: Zhao Jing , Hu De‐jun , Lao Kameng , Yang Zong‐mei , Li Shao‐ping
Published: October 2013

This article presents an overview of the advance of CE and CEC in phytochemical analysis, based on the literature not mentioned in our previous review papers [Chen, X. J., Zhao, J., Wang, Y. T., Huang, L. Q., Li, S. P., Electrophoresis 2012, 33, 168–179], mainly covering the years 2012–2013. In this article, attention is paid to online preconcentration, rapid separation, and sensitive detection. Selected examples illustrate the applicability of CE and CEC in biomedical, pharmaceutical, environmental, and food analysis. Finally, some general conclusions and future perspectives are given.
Developments in coupled solid‐phase extraction–capillary electrophoresis 2011–2013
Authors: Ramautar Rawi , Somsen Govert W. , de Jong Gerhardus J.
Published: October 2013

This article presents an overview of the design and application of coupled SPE–CE systems that have been reported in the literature between January 2011 and June 2013. The present paper is an update of three previous review papers covering the years 2000–2011 (Electrophoresis 2008, 29, 108–128; Electrophoresis 2010, 31, 44–54; Electrophoresis 2012, 33, 243–250). The use of in‐line and on‐line SPE–CE approaches is described in this review. Emerging technological developments, such as the use of in‐line frit‐free SPE and chip‐based SPE for extraction of sample components prior to CE analysis, are outlined. Selected examples illustrate the applicability of SPE–CE in biomedical, pharmaceutical, and environmental analysis. A complete overview of recent SPE–CE studies is given in table format, providing information on sample type, SPE sorbent, coupling mode, detection mode, and LOD. Finally, some general conclusions and future perspectives are provided.
Multiplex ligase‐based genotyping methods combined with CE
Authors: Shin Gi Won , Chung Boram , Jung Gyu Yong , Jung Gyoo Yeol
Published: October 2013

In this genomic era, the ability to assay multiple genomic hot spots that have strong clinical implications is greatly desired. Conventional PCR‐based methods suffer from frequent false‐positive detections, particularly when a multiplex analysis is desirable. As an alternative to the error‐prone conventional methods, multiplex ligase‐based genotyping methods combined with CE have a strong potential. In this review, both previously developed methods and emerging methods are described to reveal the specificity, sensitivity, and simplicity of the ligase‐based methods. For each step (ligation, amplification, and separation), the principles of several alternative methods are discussed along with their applications to explore the future development of ligase‐based diagnostic methods.
N‐methyl‐2‐pyrrolidonium methyl sulfonate acidic ionic liquid as a new dynamic coating for separation of basic proteins by capillary electrophoresis
Authors: Guo Xiao‐Feng , Chen Hui‐Ying , Zhou Xiao‐Hai , Wang Hong , Zhang Hua‐Shan
Published: October 2013

A simple and economical CE method has been developed for the analysis of four model basic proteins by employing N‐methyl‐2‐pyrrolidonium methyl sulfonate ionic liquid (IL) as the dynamic coating material based on the interaction of both between electrostatic attraction and hydrogen bond, and between the organic cations of IL and the inner surface of bare fused‐silica capillary. The N‐methyl‐2‐pyrrolidonium‐based IL modified capillary not only generated a stable suppressed electroosmotic flow, but also effectively eliminated the wall adsorption of proteins. Several important parameters such as the IL concentration, pH values, and concentrations of the background electrolyte were optimized to improve the separation of basic proteins. Consequently, under the optimum separation conditions, a satisfied separation of basic proteins including lysozyme, cytochrome c, ribonuclease A, and α‐chymotrypsinogen A with theoretical plates ranging from 2.09 × 105 to 4.48 × 105 plates/m had been accomplished within 15 min. The proposed method first illustrated the effect of hydrogen bond between coating material and inner capillary surface on the coating, which should be a new strategy to design and select more effective coating materials to form more stable coatings in CE.
Applications of capillary electrophoresis in characterizing recombinant protein therapeutics
Authors: Zhao Shuai Sherry , Chen David D. Y.
Published: October 2013

The use of recombinant protein for therapeutic applications has increased significantly in the last three decades. The heterogeneity of these proteins, often caused by the complex biosynthesis pathways and the subsequent PTMs, poses a challenge for drug characterization to ensure its safety, quality, integrity, and efficacy. CE, with its simple instrumentation, superior separation efficiency, small sample consumption, and short analysis time, is a well‐suited analytical tool for therapeutic protein characterization. Different separation modes, including CIEF, SDS‐CGE, CZE, and CE‐MS, provide complementary information of the proteins. The CE applications for recombinant therapeutic proteins from the year 2000 to June 2013 are reviewed and technical concerns are discussed in this article.
Electrolyte system strategies for anionic isotachophoresis with electrospray‐ionization mass‐spectrometric detection. 2. Isotachophoresis in moving‐boundary systems
Authors: Gebauer Petr , Malá Zdena , Boček Petr
Published: October 2013

This contribution is the second part of the project on strategies used in the selection of electrolyte systems for anionic ITP with ESI‐mass spectrometric detection. It presents ITP as a powerful tool for selective stacking of anionic analytes, performed in a nonconventional way in moving‐boundary systems where two co‐anions are present in both the leading and terminating zones. The theoretical background is given to substantiate the conditions for the existence and migration of ITP boundaries in moving‐boundary systems and stacking of analytes at these boundaries. The practical aspects of the theory are shown in form of stacking‐window diagrams that bring immediate information about which analytes are stacked in a given system. The presented theory and strategy are illustrated and verified on the example of analysis of a model mixture of salicylic acid, ibuprofen and diclofenac, and comparison of regular and free‐acid ITP with moving‐boundary ITP systems formed by formic and propionic acids and ammonium as counterion.
DNA glycosylases search for and remove oxidized DNA bases
Authors: Wallace Susan S.
Published: October 2013

This review article presents, an overview of the DNA glycosylases that recognize oxidized DNA bases using the Fpg/Nei family of DNA glycosylases as models for how structure can inform function. For example, even though human NEIL1 and the plant and fungal orthologs lack the zinc finger shown to be required for binding, DNA crystal structures revealed a “zincless finger” with the same properties. Moreover, the “lesion recognition loop” is not involved in lesion recognition, rather, it stabilizes 8‐oxoG in the active site pocket. Unlike the other Fpg/Nei family members, Neil3 lacks two of the three void‐filling residues that stabilize the DNA duplex and interact with the opposite strand to the damage which may account for its preference for lesions in single‐stranded DNA. Also single‐molecule approaches show that DNA glycosylases search for their substrates in a sea of undamaged DNA by using a wedge residue that is inserted into the DNA helix to probe for the presence of damage. Environ. Mol. Mutagen. 54:691–704, 2013. © 2013 Wiley Periodicals, Inc.
Inhibition of p38 MAPK sensitizes tumour cells to cisplatin‐induced apoptosis mediated by reactive oxygen species and JNK
Authors: Pereira Lorena , Igea Ana , Canovas Begoña , Dolado Ignacio , Nebreda Angel R.
Published: October 2013

The p38 MAPK pathway is an important regulator of many cellular responses. It is well established that p38 MAPK signalling negatively regulates epithelial cell transformation, but enhanced p38 MAPK activity has been also correlated with bad clinical prognosis in some tumour types. Here, we provide genetic and pharmacological evidence showing that p38 MAPK inhibition cooperates with the chemotherapeutic agent cisplatin to kill tumour cells. We show that p38 MAPK inhibition results in ROS upregulation, which in turn activates the JNK pathway via inactivation of phosphatases, sensitizing human tumour cells to cisplatin‐induced apoptosis. Using a mouse model for breast cancer, we confirm that inhibition of p38 MAPK cooperates with cisplatin treatment to reduce tumour size and malignancy in vivo. Taken together, our results illustrate a new function of p38 MAPK that helps tumour cells to survive chemotherapeutic drug treatments, and reveal that the combination of p38 MAPK inhibitors with cisplatin can be potentially exploited for cancer therapy.
mRNA 3′end processing: A tale of the tail reaches the clinic
Authors: Hollerer Ina , Grund Kerstin , Hentze Matthias W. , Kulozik Andreas E
Published: October 2013

Recent advances reveal mRNA 3′end processing as a highly regulated process that fine‐tunes posttranscriptional gene expression. This process can affect the site and/or the efficiency of 3′end processing, controlling the quality and the quantity of substrate mRNAs. The regulation of 3′end processing plays a central role in fundamental physiology such as blood coagulation and innate immunity. In addition, errors in mRNA 3′end processing have been associated with a broad spectrum of human diseases, including cancer. We summarize and discuss the paradigmatic shift in the understanding of 3′end processing as a mechanism of posttranscriptional gene regulation that has reached clinical medicine.
Optimization and Analysis of High‐Power Hydrogen/Bromine‐Flow Batteries for Grid‐Scale Energy Storage
Authors: Cho Kyu Taek , Albertus Paul , Battaglia Vincent , Kojic Aleksandar , Srinivasan Venkat , Weber Adam Z.
Published: October 2013

For storage of grid‐scale electrical energy, redox‐flow batteries (RFBs) are considered promising technologies. This paper explores the influence of electrolyte composition and ion transport on cell performance by using an integrated approach of experiments and cost modeling. In particular, the impact of the area‐specific resistance on system capability is elucidated for the hydrogen/bromine RFB. The experimental data demonstrate very good performance with 1.46 W cm−2 peak power and 4 A cm−2 limiting current density at ambient conditions for an optimal cell design and reactant concentrations. The data and cost model results show that higher concentrations of RFB reactants do not necessarily result in lower capital cost as there is a tradeoff between cell performance and storage (tank) requirements. In addition, the discharge time and overall efficiency demonstrate nonlinear effects on system cost, with a 3 to 4 hour minimum discharge time showing a key transition to a plateau in terms of cost for typical RFB systems. The presented results are applicable to many different RFB chemistries and technologies and highlight the importance of ohmic effects and associated area‐specific resistance on RFB viability.
Nonlinear response estimates of RC frames using linear analysis of SDOF systems
Authors: Yaghmaei‐Sabegh Saman , Neekmanesh Shabnam , Lumantarna Elisa
Published: October 2013

An approximate‐simple method for nonlinear response estimates of reinforced concrete frames subjected to near‐field and far‐field records is presented in this paper. The approximate method is based on equivalent single‐degree‐of‐freedom and linear multi‐degree‐of‐freedom models. In this procedure, the nonlinear maximum roof displacement is estimated using an effective period factor and elastic response spectrum with an equivalent damping. The effective period factor was proposed for far‐field and near‐field ground motion records. For regions of high seismicity, the maximum roof displacement can be estimated by applying an effective period factor of 2.3 and 2.1 for near‐field and far‐field records, respectively, and 9% damped displacement response spectrum. For regions of moderate seismicity, a lower effective period factor of 1.9 and 1.8, for near‐field and far‐field records, respectively, can be applied to estimate the maximum roof displacement. A relationship between linear and nonlinear response of multi‐degree‐of‐freedom systems was also proposed to obtain estimates of the maximum inter‐story drift of nonlinear responding reinforced concrete frames. In addition, the effects of number of ground motion records used in the analyses on the scatters of results were investigated. The required number of ground motions to produce a reliable response was proposed. Copyright © 2013 John Wiley & Sons, Ltd.
Post‐fire bedload sediment delivery across spatial scales in the interior western United States
Authors: Wagenbrenner Joseph W. , Robichaud Peter R.
Published: October 2013

Post‐fire sediment yields can be up to three orders of magnitude greater than sediment yields in unburned forests. Much of the research on post‐fire erosion rates has been at small scales (100 m2 or less), and post‐fire sediment delivery rates across spatial scales have not been quantified in detail. We developed relationships for post‐fire bedload sediment delivery rates for spatial scales up to 117 ha using sediment yield data from six published studies and two recently established study sites. Sediment yields and sediment delivery ratios (SDRs; sediment delivered at the catchment scale divided by the sediment delivered from a plot nested within the catchment) were related to site factors including rainfall characteristics, area, length, and ground cover. Unit‐area sediment yields significantly decreased with increasing area in five of the six sites. The annual SDRs ranged from 0.0089 to 1.15 and these were more closely related to the ratio of the plot lengths than the ratio of plot areas. The developed statistical relationships will help quantify post‐fire sediment delivery rates across spatial scales in the interior western United States and develop process‐based scaling relationships. Published in 2013. This article is a U.S. Government work and is in the public domain in the USA.
A new approach for the laboratory culture of the fathead minnow, Pimephales promelas
Authors: Gordon Denise A. , Smith Mark E. , Wratschko Melissa , Agard David , Holden Lisa , Wilcox Steve , Lazorchak James M.
Published: October 2013

Fathead minnows are routinely cultured for use in aquatic toxicology studies. A new mass culture system described in the present study consisted of 6 stainless steel tanks, each containing 68 fish and 20 spawning substrates. Spawning results are compared with a previous system of 22 individual glass aquaria, which contained 16 fish and 4 spawning substrates per tank. During a 19-mo period, the new system produced an average of 4105 eggs/d, compared with an average of 2465 eggs/d with the previous system. Labor and maintenance were reduced with the new system. The stainless steel tanks eliminated aquaria glass breakage, and daily water use was reduced by 45%. Analysis of reference toxicant data from fish cultured using both systems indicated no change in the sensitivity of the test animals. Analyses of 2009 egg production data determined that a 6:1 to 7:1 female to male ratio had a significantly positive impact on egg production levels and that 6-mo-old breeding stock should be introduced to the spawning tanks in mid-spring for optimal egg production during the rest of the year. Implementing a stainless steel mass culture system significantly increased efficiency of egg production; reduced turnaround delay of mature animal availability for toxicity and molecular testing; and reduced labor time, costs, and inherent safety hazards, compared with glass aquaria systems. Environ Toxicol Chem 2014;33:126–133. © 2013 SETAC
The impact of municipal wastewater effluent on field-deployed freshwater mussels in the Grand River (Ontario, Canada)
Authors: Gillis Patricia L. , Gagné François , McInnis Rodney , Hooey Tina M. , Choy Emily S. , André Chantale , Hoque Md Ehsanul , Metcalfe Chris D.
Published: October 2013

To examine effects of municipal wastewater effluent (MWWE) on sentinel organisms, the authors deployed caged freshwater mussels (Lasmigona costata) in the Grand River (ON, Canada) upstream and downstream of an MWWE outfall. Passive sampling devices were deployed alongside caged mussels to confirm exposure. Biomarkers of xenobiotic biotransformation, oxidative stress, estrogenicity, and immunomodulation were investigated. Elevated concentrations of selected pharmaceutical and personal care products (PPCPs) and a natural estrogen (estrone) were found at the downstream sites. Mussels caged downstream of the effluent for 2 wk showed minimal evidence of exposure, while those deployed for 4 wk exhibited significantly higher levels of lipid peroxidation (LPO) and glutathione S-transferase (GST) activity, demonstrating that MWWE-exposed mussels exhibit increased activity in xenobiotic conjugation and oxidative stress. With respect to immune responses, a significant increase in plasma lysozyme activity and hemocyte viability was observed in MWWE-exposed mussels. Vitellogenin (vtg)-like protein in male mussels showed a trend toward induction after 4 wk of deployment at the first downstream site, but mean levels were not significantly different. Discriminant function analysis indicated that mussels deployed for 4 wk upstream and downstream of the MWWE discharge could be discriminated on the basis of LPO, GST, plasma lysozyme, and vtg responses. The physiological stress observed in caged mussels indicates that wild mussels chronically exposed to MWWE in this ecosystem would also be negatively impacted. Environ Toxicol Chem 2014;33:134–143. © 2013 SETAC
Age-related polychlorinated biphenyl dynamics in immature bull sharks (Carcharhinus leucas)
Authors: Olin Jill A. , Beaudry Marina , Fisk Aaron T. , Paterson Gordon
Published: October 2013

Polychlorinated biphenyls (PCBs) were quantified in liver tissues of bull sharks (Carcharhinus leucas) ranging in age from <4 wk to >3 yr. Summed values of PCBs (ΣPCBs) ranged from 310 ng/g to 22 070 ng/g (lipid wt) across age classes with ΣPCB concentrations for the youngest sharks in the present study (<4 wk; 5230 ± 2170 ng/g lipid wt) determined to not significantly differ from those quantified in >3-yr-old sharks, highlighting the extent of exposure of this young life stage to this class of persistent organic pollutants (POPs). Age normalization of PCB congener concentrations to those measured for the youngest sharks demonstrated a significant hydrophobicity (log octanol/water partition coefficient [KOW]) effect that was indicative of maternal offloading of highly hydrophobic (log KOW ≥6.5) congeners to the youngest individuals. A distinct shift in the PCB congener profiles was also observed as these young sharks grew in size. This shift was consistent with a transition from the maternally offloaded signal to the initiation of exogenous feeding and the contributions of mechanisms including growth dilution and whole-body elimination. These results add to the growing pool of literature documenting substantially high concentrations of POPs in juvenile sharks that are most likely attributable to maternal offloading. Collectively, such results underscore the potential vulnerability of young sharks to POP exposure and pose additional concerns for shark-conservation efforts. Environ Toxicol Chem 2014;33:35–43. © 2013 SETAC
Investigating Alternatives to the fish early-life stage test: A strategy for discovering and annotating adverse outcome pathways for early fish development
Authors: Villeneuve Daniel , Volz David C. , Embry Michelle R. , Ankley Gerald T. , Belanger Scott E. , Léonard Marc , Schirmer Kristin , Tanguay Robert , Truong Lisa , Wehmas Leah
Published: October 2013

The fish early-life stage (FELS) test (Organisation for Economic Co-operation and Development [OECD] test guideline 210) is the primary test used internationally to estimate chronic fish toxicity in support of ecological risk assessments and chemical management programs. As part of an ongoing effort to develop efficient and cost-effective alternatives to the FELS test, there is a need to identify and describe potential adverse outcome pathways (AOPs) relevant to FELS toxicity. To support this endeavor, the authors outline and illustrate an overall strategy for the discovery and annotation of FELS AOPs. Key events represented by major developmental landmarks were organized into a preliminary conceptual model of fish development. Using swim bladder inflation as an example, a weight-of-evidence–based approach was used to support linkage of key molecular initiating events to adverse phenotypic outcomes and reduced young-of-year survival. Based on an iterative approach, the feasibility of using key events as the foundation for expanding a network of plausible linkages and AOP knowledge was explored and, in the process, important knowledge gaps were identified. Given the scope and scale of the task, prioritization of AOP development was recommended and key research objectives were defined relative to factors such as current animal-use restrictions in the European Union and increased demands for fish toxicity data in chemical management programs globally. The example and strategy described are intended to guide collective efforts to define FELS-related AOPs and develop resource-efficient predictive assays that address the toxicological domain of the OECD 210 test. Environ Toxicol Chem 2014;33:158–169. © 2013 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited.
Optical bioassay for measuring sublethal toxicity of insecticides in Daphnia pulex
Authors: Zein Maya A. , McElmurry Shawn P. , Kashian Donna R. , Savolainen Peter T. , Pitts David K.
Published: October 2013

Many emerging contaminants tend to be biologically active at very low concentrations, occur in water as part of complex mixtures, and impact biota in ways that are not detected using traditional toxicity tests (e.g., median lethal concentration). To evaluate emerging contaminants, the authors developed a method for detecting sublethal behavioral effects by quantifying the swimming behavior of Daphnia pulex, a model organism for studying aquatic toxicity. This optical tracking technique is capable of measuring many swimming parameters, 2 of which—cumulative distance and angular change—are presented. To validate this technique, 2 prototypical compounds that exhibit different modes of action as well as corresponding insecticides that are commonly found in surface waters were investigated. The acetylcholinesterase (AChE) inhibitor physostigmine was used as the prototypical compound for the large number of AChE inhibitor insecticides (e.g., chlorpyrifos). Nicotine was used as the prototypical compound for neonicotinoid insecticides (e.g., imidacloprid). Results demonstrate that this assay is capable of detecting sublethal behavioral effects that are concentration-dependent and that insecticides with the same mode of action yield similar results. The method can easily be scaled up to serve as a high-throughput screening tool to detect sublethal toxic effects of a variety of chemicals. This method is likely to aid in enhancing the current understanding of emerging contaminants and to serve as a novel water-quality screening tool. Environ Toxicol Chem 2014;33:144–151. © 2013 SETAC
Does a concomitant exposure to lead influence unfavorably the naphthalene subchronic toxicity and toxicokinetics?
Authors: Katsnelson Boris A. , Minigaliyeva Ilzira A. , Degtyareva Tamara D. , Privalova Larisa I. , Beresneva Tatyana A.
Published: October 2013

Rats were given 20 times during 40 d either naphthalene per gavage or the same and lead acetate intraperitoneally in single doses corresponding to 5% of the respective 50% lethal doses. The concomitant exposure to lead not only added some typical indicators of lead toxicity to the moderate naphthalene intoxication picture but also exaggerated some less specific indices for intoxication. However, a number of such indices testified to attenuation of naphthalene's adverse effects under the impact of lead. Lead also lowered urinary excretion of both total and conjugated naphthalene, while the free- to total naphthalene ratio in urine sharply increased. These results corroborate implicitly the initial hypothesis that lead, being an inhibitor of cytochrome P450, hinders phase I of the naphthalene biotransformation and, thus, the formation of derivates which can be more toxic but are capable of entering into reactions of conjugation with resulting detoxication and elimination of naphthalene from the body. Environ Toxicol Chem 2014;33:152–157. © 2013 SETAC
Predicting the sensitivity of populations from individual exposure to chemicals: The role of ecological interactions
Authors: Gabsi Faten , Schäffer Andreas , Preuss Thomas G.
Published: October 2013

Population responses to chemical stress exposure are influenced by nonchemical, environmental processes such as species interactions. A realistic quantification of chemical toxicity to populations calls for the use of methodologies that integrate these multiple stress effects. The authors used an individual-based model for Daphnia magna as a virtual laboratory to determine the influence of ecological interactions on population sensitivity to chemicals with different modes of action on individuals. In the model, hypothetical chemical toxicity targeted different vital individual-level processes: reproduction, survival, feeding rate, or somatic growth rate. As for species interactions, predatory and competition effects on daphnid populations were implemented following a worst-case approach. The population abundance was simulated at different food levels and exposure scenarios, assuming exposure to chemical stress solely or in combination with either competition or predation. The chemical always targeted one vital endpoint. Equal toxicity-inhibition levels differently affected the population abundance with and without species interactions. In addition, population responses to chemicals were highly sensitive to the environmental stressor (predator or competitor) and to the food level. Results show that population resilience cannot be attributed to chemical stress only. Accounting for the relevant ecological interactions would reduce uncertainties when extrapolating effects of chemicals from individuals to the population level. Validated population models should be used for a more realistic risk assessment of chemicals. Environ Toxicol Chem 2014;33:1449–1457. © 2014 SETAC
Influence of carbon nanotubes with preloaded and coexisting dissolved organic matter on the bioaccumulation of polycyclic aromatic hydrocarbons to Chironomus plumosus larvae in sediment
Authors: Shen Mohai , Xia Xinghui , Zhai Yawei , Zhang Xiaotian , Zhao Xiuli , Zhang Pu
Published: October 2013

The ubiquity of dissolved organic matter (DOM) in an aqueous environment may have influence on the carbonaceous material's impact on the bioaccumulation of polycyclic aromatic hydrocarbons (PAHs) to benthonic organisms in contaminated sediment. In the present study, 1 multiwalled carbon nanotube (MWNT); 2 types of DOM (fulvic acid and tannic acid), and 2 PAHs (pyrene and chrysene) were selected to study the influence of MWNT with preloaded and coexisting DOM on the bioaccumulation of PAHs to Chironomus plumosus larvae in sediment. Moreover, the freely dissolved concentrations of PAHs were measured to explore the influence mechanisms. The results showed that despite the presence or absence of preloaded or coexisting DOM, the presence of 1% MWNT in sediments suppressed the biota-sediment accumulation factor (BSAF) and elevated the water-based bioaccumulation factor (BAF) of PAHs. However, the BSAF and BAF values generally decreased with the increase of 2 forms of both DOM; this was caused by the combined impact of DOM and MWNT on the freely dissolved concentrations of PAHs and the ingestion behavior of benthic organisms. Environ Toxicol Chem 2014;33:182–189. © 2013 SETAC