bluuebunny/crossref_metadata_2025 huggingface dataset:
ChemInform Abstract: Samarium(III) Triflate as an Efficient and Reusable Catalyst for Facile Synthesis of Benzoxazoles and Benzothiazoles in Aqueous Medium.
Authors: Gorepatil Pratapsinha B. , Mane Yogesh D. , Ingle Vilas S.
Published: February 2014

Water‐tolerant samarium triflate is found to be a suitable catalyst for the condensation of o‐aminophenols and o‐aminothiophenols with various aldehydes in aqueous ethanol.
ChemInform Abstract: Palladium‐Catalyzed β‐Arylation of Silyl Ketene Acetals and Application to the Synthesis of Benzo‐Fused δ‐Lactones.
Authors: Aspin Sam , Lopez‐Suarez Laura , Larini Paolo , Goutierre Anne Sophie , Jazzar Rodolphe , Baudoin Olivier
Published: February 2014

Silyl ketene acetals show enhanced chemoselectivity as nucleophiles in Pd‐catalyzed migrative C(sp3)‐H arylations with aryl bromides to give arylpropionic acid esters in good yields.
ChemInform Abstract: Organocatalytic Enantioselective γ‐Aminoalkylation of Unsaturated Ester: Access to Pipecolic Acid Derivatives.
Authors: Xu Jianfeng , Jin Zhichao , Chi Yonggui Robin
Published: February 2014

A NHC‐catalyzed cyclocondensation of α,β‐unsaturated esters with hydrazones of type (II) is developed to yield enantioenrichend δ‐lactams.
ChemInform Abstract: Pd(II)‐Catalyzed One‐Pot, Three‐Step Route for the Synthesis of Unsymmetrical Acridines.
Authors: Guo Hai‐Ming , Mao Run‐Ze , Wang Qiao‐Tian , Niu Hong‐Ying , Xie Ming‐Sheng , Qu Gui‐Rong
Published: February 2014

A one‐pot amination/cyclization/aromatization sequence is described to construct substituted acridines from 2‐formylphenyl triflates and electron rich anilines in the presence of Pd(II)/XPhos as the catalyst.
ChemInform Abstract: Enantioselective 1,3‐Dipolar Cycloaddition of C,N‐Cyclic Azomethine Imines to Unsaturated Nitriles Catalyzed by NiII—Pigiphos.
Authors: Milosevic Sandra , Togni Antonio
Published: February 2014

The new asymmetric cycloaddition reaction of cyclic azomethine imines with small unsaturated nitriles uses a dicationic Ni(II) complex as a catalyst.
ChemInform Abstract: Cascade Reaction Synthesis of Multisubstituted Bicyclic Pyridone Derivatives.
Authors: Chen Xuebing , Zhu Dandan , Wang Xiaoying , Yan Shengjiao , Lin Jun
Published: February 2014

A novel, efficient, economical, and environmentally friendly synthesis allows the preparation of a wide range of different functionalized bicyclic pyridone derivatives under mild reaction conditions.
ChemInform Abstract: Synthesis and Photochromic Properties of Quinoxalino[e]‐Anellated Dimethyldihydropyrene with Planar Chirality.
Authors: Sawada Tsuyoshi , Kihara Takao , Fujikawa Yuya , Narazaki Yu
Published: February 2014

Due to its photochemical properties compound (IV) could be used as a photo responsive circularly polarized emission material.
ChemInform Abstract: N‐Heterocyclic Carbenes Mediated Cyano‐Phosphorylation of Ketones.
Authors: He Lin , Zhang Jing , Fan Ye‐Cheng , Du Guang‐Fen , Zhang Jie , Dai Bin
Published: February 2014

The title reaction affords various different substituted cyanohydrin‐O‐phosphates under mild conditions and the reaction can be easily scaled‐up.
ChemInform Abstract: Functionalized Alkenylzinc Reagents Bearing Carbonyl Groups: Preparation by Direct Metal Insertion and Reaction with Electrophiles.
Authors: Saemann Christoph , Schade Matthias A. , Yamada Shigeyuki , Knochel Paul
Published: February 2014

The present protocol avoids the drawbacks of established procedures, namely low reaction temperatures and use of expensive alkenyl iodides.
ChemInform Abstract: Progress Toward the Total Synthesis of Bielschowskysin.
Authors: Townsend Steveen D. , Sulikowski Gary A.
Published: February 2014

The stereocontrolled introduction of the C6 and C12 vicinal quarternary centers via a [2 + 2]‐photocycloaddition is reported.
ChemInform Abstract: Preparation of Spiro[4.4]oxaphospholene and ‐azaphospholene Systems from Carbohydrate Templates.
Authors: Moura Marina , Josse Solen , Postel Denis
Published: February 2014

Some new title compounds such as (IV), (VI), (VIII), and (XI) are prepared in order to test their biological activity.
ChemInform Abstract: Regioselective Silyl/Acetate Exchange of Disaccharides Yields Advanced Glycosyl Donor and Acceptor Precursors.
Authors: Hsieh Hsiao‐Wu , Schombs Matthew W. , Witschi Mark A. , Gervay‐Hague Jacquelyn
Published: February 2014

Acid concentration, thermal conditions, and microwave assistance mediate the silyl/acetate exchange reaction.
ChemInform Abstract: Inhibitory Constituents from the Aerial Parts of Polygala tenuifolia on LPS‐Induced NO Production in BV2 Microglia Cells
Authors: Shi Tian‐Xing , Wang Shu , Zeng Ke‐Wu , Tu Peng‐Fei , Jiang Yong
Published: February 2014

isolation, structure determination and evaluation of inhibitory effects of five new phenolic glycosides, tenuisides A—E (I)—(III), new megastigmane glycoside, tenuiside F (IV), and seventeen known compounds on NO production in LPS‐activated BV‐2 microglia cells
ChemInform Abstract: Novel Ring A Rearranged Isomers with γ‐Lactone from the Fruits of Aphanamixis grandifolia.
Authors: Wang Xiao‐Bing , Zhang Yao , Wang Jun‐Song , Gu Yu‐Cheng , Kong Ling‐Yi
Published: February 2014

Aphagranols A (I) and B (II) are isolated and their structure is determined using spectroscopic methods and confirmed by comparison to their acetylated derivative.
ChemInform Abstract: Sydowiols A—C (I): Mycobacterium tuberculosis Protein Tyrosine Phosphatase (PtpA) Inhibitors from an East China Sea Marine‐Derived fungus, Aspergillus sydowii.
Authors: Capon Robert J. , et al. et al.
Published: February 2014

The sydowiols A (Ia) and C (Ic) are identified as M.
ChemInform Abstract: Enantioselective Syntheses of FR901464 (Ib) and Spliceostatin A (Ia): Potent Inhibitors of Spliceosome.
Authors: Ghosh Arun K. , Chen Zhi‐Hua
Published: February 2014

A short and improved synthesis of the title compounds is presented in 19 and 20 total steps, respectively.
ChemInform Abstract: Additional Cytotoxic Substances Isolated from the Sponge‐Derived Gymnascella dankaliensis.
Authors: Amagata Taro , Tanaka Makoto , Yamada Takeshi , Chen Yi‐Pei , Minoura Katsuhiko , Numata Atsushi
Published: February 2014

Dankastin C (I) shows potent cell growth inhibitory activity against the murine P388 cell line.
ChemInform Abstract: Lithium—Sulfur Batteries: Electrochemistry, Materials, and Prospects
Authors: Yin Ya‐Xia , Xin Sen , Guo Yu‐Guo , Wan Li‐Jun
Published: February 2014

Review: 127 refs.
ChemInform Abstract: Toward a Green Way for the Chemical Production of Supported Graphenes Using Porous Solids
Authors: Ruiz‐Garcia Cristina , Darder Margarita , Aranda Pilar , Ruiz‐Hitzky Eduardo
Published: February 2014

Review: 94 refs.
ChemInform Abstract: Low Temperature Ordering in Easy‐axis S = 1 Kagome and Triangular Lattice Antiferromagnets
Authors: Damle Kedar
Published: February 2014

Review: 25 refs.
ChemInform Abstract: Molecular Engineering of Functional Inorganic and Hybrid Materials
Authors: Sanchez C. , et al. et al.
Published: February 2014

Review: 328 refs.
ChemInform Abstract: Zeolites from a Materials Chemistry Perspective
Authors: Davis Mark E.
Published: February 2014

Review: 72 refs.
ChemInform Abstract: Synthesis Strategies for Preparing Useful Small Pore Zeolites and Zeotypes for Gas Separations and Catalysis
Authors: Moliner Manuel , Martinez Cristina , Corma Avelino
Published: February 2014

Review: 113 refs.
ChemInform Abstract: Nanoporous Solids: How Do They Form? An in situ Approach
Authors: Ferey Gerard , Haouas Mohamed , Loiseau Thierry , Taulelle Francis
Published: February 2014

Review: focus on in situ NMR spectroscopy of the soluble species present in syntheses media during crystallization; 81 refs.
ChemInform Abstract: Boronic Esters in Asymmetric Synthesis
Authors: Matteson Donald S.
Published: February 2014

Review: 133 refs.
ChemInform Abstract: Metalation Dictates Remote Regioselectivity: Ruthenium‐Catalyzed Functionalization of meta CAr—H Bonds.
Authors: Julia‐Hernandez Francisco , Simonetti Marco , Larrosa Igor
Published: February 2014

Review: 12 refs.
ChemInform Abstract: β‐Keto Sulfones: Preparation and Application in Organic Synthesis
Authors: Markitanov Yuriy M. , Timoshenko Vadim M. , Shermolovich Yuriy G.
Published: February 2014

Review: 200 refs.
ChemInform Abstract: Recent Applications of Organic Dyes as Photoredox Catalysts in Organic Synthesis
Authors: Nicewicz David A. , Nguyen Tien M.
Published: February 2014

Review: 28 refs.
ChemInform Abstract: (‐)‐Cytisine and Derivatives: Synthesis, Reactivity, and Applications
Authors: Rouden Jacques , Lasne Marie‐Claire , Blanchet Jerome , Baudoux Jerome
Published: February 2014

Review: 656 refs.
ChemInform Abstract: Carbon—Carbon Bond Formation Through Palladium Homoenolates
Authors: Nithiy Nisha , Rosa David , Orellana Arturo
Published: February 2014

Review: 62 refs.
ChemInform Abstract: Synthesis and Uses of Fluorous and Highly Fluorinated Macrocyclic and Spherical Molecules
Authors: Yi Wen‐Bin , Ma Jing‐Jing , Jiang Lv‐Qi , Cai Chun , Zhang Wei
Published: February 2014

Review: 77 refs.
ChemInform Abstract: Base‐Catalyzed Mukaiyama‐Type Aldol Additions, a Continued Quest for Stereoselectivity
Authors: Sutar Revannath L. , Joshi Navalkishore N.
Published: February 2014

Review: 122 refs.
ChemInform Abstract: Mechanistic and Kinetic Aspects of Pentose Dehydration Towards Furfural in Aqueous Media Employing Homogeneous Catalysis
Authors: Danon Bart , Marcotullio Gianluca , de Jong Wiebren
Published: February 2014

Review: 115 refs.
ChemInform Abstract: Drug Discovery Considerations in the Development of Covalent Inhibitors
Authors: Mah Robert , Thomas Jason R. , Shafer Cynthia M.
Published: February 2014

Review: 71 refs.
ChemInform Abstract: Ion Conducting Membranes for Fuel Cells and Other Electrochemical Devices
Authors: Kreuer Klaus‐Dieter
Published: February 2014

Review: 118 refs.
ChemInform Abstract: Waste Tire Pyrolysis — A Review
Authors: Martinez Juan Daniel , Puy Neus , Murillo Ramon , Garcia Tomas , Navarro Maria Victoria , Mastral Ana Maria
Published: February 2014

Review: 209 refs.
ChemInform Abstract: Evaluation of Biochars by Temperature Programmed Oxidation/Mass Spectrometry
Authors: Jackson Michael A. , Eberhardt Thomas L. , Boateng Akwasi A. , Mullen Charles A. , Groom Leslie H.
Published: February 2014

Review: 34 refs.
A β‐Lactone‐Based Antivirulence Drug Ameliorates Staphylococcus aureus Skin Infections in Mice
Authors: Weinandy Franziska , Lorenz‐Baath Katrin , Korotkov Vadim S. , Böttcher Thomas , Sethi Shneh , Chakraborty Trinad , Sieber Stephan A.
Published: February 2014

Skin infections caused by Staphylococcus aureus are a major clinical concern, especially if they are caused by multi‐resistant strains. In these cases, a spread into deeper soft tissues or the bloodstream results in life‐threatening conditions that are difficult to treat by conventional antibiotics. Previous in vitro experiments with a small β‐lactone‐based molecule demonstrated that antibiotic‐sensitive and ‐resistant S. aureus strains are effectively disarmed in their virulence and corresponding pathogenicity. In this work, in vivo mouse studies show that this methodology is effective for the treatment of skin abscesses in mice. A single dose of the β‐lactone significantly decreased abscess size even when applied 6 h post‐infection. Although the molecule requires pharmacological optimization (improved stability, for example), this study emphasizes the potential value of antivirulence therapies.
Comparison of secondary and primary thyroid cancer in adolescents and young adults
Authors: Goldfarb Melanie , Freyer David R.
Published: February 2014

BACKGROUND

Thyroid cancer is one of the 5 most common malignancies in adolescent and young adult (AYA) patients (ages 15‐39 years) and may develop de novo or in patients previously treated for cancer. This study compared the tumor characteristics, treatment, and overall survival (OS) of secondary malignant neoplasm (SMN) versus primary thyroid cancer in AYA patients.

METHODS

All cases of AYA thyroid cancer contained in the 1998 to 2010 American College of Surgeons National Cancer Database were divided into 2 cohorts according to primary or secondary occurrence. Comparisons using appropriate statistical methods were performed.

RESULTS

Of 41,062 cases, 1349 (3.3%) had experienced a prior malignancy. Compared with cases of primary thyroid cancer, SMNs were more likely multifocal (odds ratio [OR] = 1.173, 95% confidence interval [CI] = 1.049‐1.313) microcarcinomas < 1 cm (OR = 1.496, 95% CI = 1.327‐1.687) with tall/columnar cells (OR = 2.187, 95% CI = 0.534‐0.692), of white race (OR = 2.643, 95% CI = 1.310‐5.331) and age 35‐39 years (OR = 1.239, 95% CI = 1.093‐1.404) and less likely female (OR = 0.608, 95% CI = 0.534‐0.692), Hispanic (OR = 0.779, 95% CI = 0.642‐0.946) age 15‐19 years (OR = 0.624, 95% CI = 0.510‐0.763) or 25‐29 years (OR = 0.711, 95% CI = 0.604‐0.837), or less likely > 4 cm in size (OR = 0.610, 95% CI = 0.493‐0.758). There was a 6.63‐fold (95% CI = 4.97‐8.86, P < .001) relative risk of death for secondary versus primary thyroid cancers after adjusting for demographic, tumor, and thyroid treatment factors. Only Hispanic origin, tall/columnar cell histology, and distant metastases decreased OS for SMNs.

CONCLUSIONS

AYAs who develop thyroid cancer as a SMN have a significantly decreased OS compared to AYAs with primary thyroid cancer. Multiple demographic and tumor differences exist between these 2 cohorts. Whether the outcome disparity results from previous cancer treatment or differences in biology, environment, or access to care are areas needing further investigation. Cancer 2014;120:1155–1161. © 2014 American Cancer Society.
Cryogenic Colocalization Microscopy for Nanometer‐Distance Measurements
Authors: Weisenburger Siegfried , Jing Bo , Hänni Dominik , Reymond Luc , Schuler Benjamin , Renn Alois , Sandoghdar Vahid
Published: February 2014

The main limiting factor in spatial resolution of localization microscopy is the number of detected photons. Recently we showed that cryogenic measurements improve the photostability of fluorophores, giving access to Angstrom precision in localization of single molecules. Here, we extend this method to colocalize two fluorophores attached to well‐defined positions of a double‐stranded DNA. By measuring the separations of the fluorophore pairs prepared at different design positions, we verify the feasibility of cryogenic distance measurement with sub‐nanometer accuracy. We discuss the important challenges of our method as well as its potential for further improvement and various applications.
Dispersion Characteristics and Aggregation in Titanate Nanowire Colloids
Authors: Horváth Endre , Grebikova Lucie , Maroni Plinio , Szabó Tamás , Magrez Arnaud , Forró László , Szilagyi Istvan
Published: February 2014

Titanate nanowires (TiONWs) are synthesized through the hydrothermal method and characterized in acidic aqueous dispersions by using electrophoresis, dynamic light scattering, and atomic force microscopy. The TiONWs have a rodlike shape with an average length of about 600 nm and a thickness of 35 nm. They are positively charged under the conditions used. Their surface charge properties and aggregation are investigated in the presence of oppositely charged poly(styrene sulfonate) (PSS) polyelectrolyte. Charge neutralization followed by a subsequent charge reversal process is observed, which is attributed to the adsorption of PSS. The colloids are unstable near the charge neutralization point and stable at lower and higher PSS doses, in good qualitative agreement with the theory developed by Derjaguin, Landau, Verwey, and Overbeek (DLVO). The nanowires prefer to align along the walls, leading to “spaghetti‐like” oriented aggregates. The aggregation processes of bare and PSS‐coated TiONWs are monitored at different concentrations of an inert electrolyte; slow aggregation is found at low salt levels, whereas aggregation is rapid beyond the critical coagulation concentration, as predicted by the DLVO theory, which describes the colloid stability of the TiONWs adequately in all the systems investigated. Coating of the nanowires with the polyelectrolyte leads to a critical coagulation concentration 75 times higher than that of the bare titanates, indicating the enormous stabilizing effect of PSS.
Experimental and Theoretical Characterization of 5,10‐Diminoporphodimethenes: Dearomatized Porphyrinoids from Palladium‐Catalyzed Hydrazinations of 5,10‐Diarylporphyrins
Authors: Bašić Bruno , Locos Oliver B. , Rintoul Llew , Kan Jinglan , Jiang Jianzhuang , Arnold Dennis P.
Published: February 2014

A new dearomatized porphyrinoid, 5,10‐diiminoporphodimethene (5,10‐DIPD), has been prepared by palladium‐catalyzed hydrazination of 5,10‐dibromo‐15,20‐bis(3,5‐di‐tert‐butylphenyl)porphyrin and its nickel(II) complex, by using ethyl and 4‐methoxybenzyl carbazates. The oxidative dearomatization of the porphyrin ring occurs in high yield. Further oxidation with 2,3‐dichloro‐5,6‐dicyanobenzoquinone forms the corresponding 5,10‐bis(azocarboxylates), thereby restoring the porphyrin aromaticity. The UV/visible spectra of the NiIIDIPDs exhibit remarkable redshifts of the lowest‐energy bands to 780 nm, and differential pulse voltammetry reveals a contracted electrochemical HOMO–LUMO gap of 1.44 V. Density functional theory (DFT) was used to calculate the optimized geometries and frontier molecular orbitals of model 5,10‐DIPDNi7cand 5,10‐bis(azocarboxylate)Ni8c. The conformations of the carbamate groups and the configurations of the CNZ unit were considered in conjunction with the NOESY spectra, to generate the global minimum geometry and two other structures with slightly higher energies. In the absence of solution data regarding conformations, ten possible local minimum conformations were considered forNi8c. Partition of the porphyrin macrocycle into tri‐ and monopyrrole fragments inNi7cand the inclusion of terminal conjugating functional groups generate unique frontier molecular orbital distributions and a HOMO–LUMO transition with a strong element of charge transfer from the monopyrrole ring. Time‐dependent DFT calculations were performed for the three lowest‐energy structures ofNi7candNi8c, and weighting according to their energies allowed the prediction of the electronic spectra. The calculations reproduce the lower‐energy regions of the spectra and the overall forms of the spectra with high accuracy, but agreement is not as good in the Soret region below 450 nm.
Isomerism of Cycloserine and Its Protonated Form
Authors: Fraschetti Caterina , Filippi Antonello , Borocci Stefano , Steinmetz Vincent , Speranza Maurizio
Published: February 2014

A comprehensive ab initio investigation has been performed on the structure and stability of the isomers of cycloserine and its protonated forms in the unsolvated state. Many conformers of cycloserine in the ketonic (K), enolic (E4 and E2), and zwitterionic (Z7 and Z2) forms have been characterized. Enols E2 are only a few kilocalories per mole less stable than the K isomers. Enols E4, as well as Z7 and Z2 zwitterions, are several tens of kilocalories per mole less stable than K. All the above isomeric structures exhibit pronounced isoxazolidine ring puckering, which generates very rich conformeric landscapes. The relative stability of the conformers of K, E2, and E4 responds essentially to a complex balance between the attractive and repulsive electrostatic interactions among their functional groups. The preferred site of protonation of cycloserine in the gas phase has been also investigated computationally and experimentally by IR multiphoton dissociation (IRMPD) spectroscopy. The most basic center of cycloserine is the N(7) nitrogen atom (proton affinity (PA)=215.3 kcal mol−1). Another important basic site is the O(6) oxygen atom (PA=213.0 kcal mol−1). Their most populated conformers have been identified by IRMPD spectroscopy. Their predominance responds to the electrostatic interactions among the functional groups of the protonated molecule.
Synthesis of Zn‐doped talc in hydrothermal atmosphere
Authors: Catalano M. , Belluso E. , Miriello D. , Barrese E. , Bloise A.
Published: February 2014

Zn‐doped talc were synthesized under hydrothermal conditions at constant reaction time and pressure of 160 hours and 2 kbar respectively, at three different temperatures (300, 500 and 650 °C) with pH‐values of 5 and 7. The starting materials and run products were characterized by X‐ray powder diffraction (XRPD), scanning electron microscopy with annexed energy‐dispersive spectrometry (SEM‐EDS), differential scanning calorimetry thermogravimetric analysis (DSC‐TG) and Fourier transform infrared (FT‐IR). The results showed that the temperature, pH‐value of the reaction mixture and amount of zinc in the starting mixture affected the growth of the Zn‐doped talc. When synthesized at low temperature talc presents low crystallinity, flawed morphology but higher content in zinc in its lattice. A thermal treatment at, or above 500 °C allowed a significant flaw reduction in talc morphology, a higher crystallinity and a lower content in dopant. When large amounts of Zn were present in the starting mixtures, Zn‐doped talc grew small in size and poorly shaped. The effect of Zn doping on some chemical/physical characteristics of the synthesized talc was also discussed.
Amine‐Functionalized Amino Acid‐based Ionic Liquids as Efficient and High‐Capacity Absorbents for CO2
Authors: Saravanamurugan Shunmugavel , Kunov‐Kruse Andreas J. , Fehrmann Rasmus , Riisager Anders
Published: February 2014

Ionic liquids (ILs) comprised of ammonium cations and anions of naturally occurring amino acids containing an additional amine group (e.g., lysine, histidine, asparagine, and glutamine) were examined as high‐capacity absorbents for CO2. An absorption capacity of 2.1 mol CO2 per mol of IL (3.5 mol CO2 per kg IL, 13.1 wt % CO2) was measured for [N66614][Lys] at ambient temperature and about 1 mol CO2 per mol of IL at 80 °C (under 1 bar of CO2). This demonstrated that desorption is possible under CO2‐rich conditions by temperature‐swing absorption; three consecutive sorption cycles were performed with the IL. The mechanistic and kinetic study of the absorption process was further substantiated by NMR spectroscopy and in situ attenuated total reflectance FTIR for [N66614][Lys] and the homologous phosphonium‐based IL [P66614][Lys]. This study revealed that carbamic acid was formed with CO2 in both ILs by chemisorption; however, the amino acid–carboxyl groups on the anion played an important—but different—catalytic role for the sorption kinetics in the two ILs. The origin of the cationic effect is speculated to be correlated with the strength of the ion interactions in the two ILs.
Preserving Particle Characteristics at Increasing Production Rate of ZnO Nanoparticles by Chemical Vapor Synthesis
Authors: Schilling Carolin , Winterer Markus
Published: February 2014

ZnO nanoparticles are synthesized by chemical vapor synthesis (CVS) via various possible routes, i.e., by increasing the total pressure, the precursor concentration, the reactor diameter, and alternatively by parallelization through the use of parallel reactors, to increase the production rate. The influence on the particle characteristics, such as size, size distribution, degree of agglomeration, and crystallinity as an integral parameter for the defect level, is investigated. It is found that only the use of parallel tubes allows an increase in the production rate while preserving particle characteristics, whereas the other routes increase the production rate at the cost of altered particle characteristics.
In search of antiaging modalities: Evaluation of mTOR‐ and ROS/DNA damage‐signaling by cytometry
Authors: Darzynkiewicz Zbigniew , Zhao Hong , Halicka H. Dorota , Li Jiangwei , Lee Yong‐Syu , Hsieh Tze‐Chen , Wu Joseph M.
Published: February 2014

This review presents the evidence in support of the IGF‐1/mTOR/S6K1 signaling as the primary factor contributing to aging and cellular senescence. Reviewed are also specific interactions between mTOR/S6K1 and ROS‐DNA damage signaling pathways. Outlined are critical sites along these pathways, including autophagy, as targets for potential antiaging (gero‐suppressive) and/or chemopreventive agents. Presented are applications of flow‐ and laser scanning‐ cytometry utilizing phospho‐specific Abs, to monitor activation along these pathways in response to the reported antiaging drugs rapamycin, metformin, berberine, resveratrol, vitamin D3, 2‐deoxyglucose, and acetylsalicylic acid. Specifically, effectiveness of these agents to attenuate the level of constitutive mTOR signaling was tested by cytometry and confirmed by Western blotting through measuring phosphorylation of the mTOR‐downstream targets including ribosomal protein S6. The ratiometric analysis of phosphorylated to total protein along the mTOR pathway offers a useful parameter reporting the effects of gero‐suppressive agents. In parallel, their ability to suppress the level of constitutive DNA damage signaling induced by endogenous ROS was measured. While the primary target of each of these agents may be different the data obtained on several human cancer cell lines, WI‐38 fibroblasts and normal lymphocytes suggest common downstream mechanism in which the decline in mTOR/S6K1 signaling and translation rate is coupled with a reduction of oxidative phosphorylation and ROS that leads to decreased oxidative DNA damage. The combined assessment of constitutive γH2AX expression, mitochondrial activity (ROS, ΔΨm), and mTOR signaling provides an adequate gamut of cell responses to test effectiveness of gero‐suppressive agents. Described is also an in vitro model of induction of cellular senescence by persistent replication stress, its quantitative analysis by laser scanning cytometry, and application to detect the property of the studied agents to attenuate the induction of senescence. Discussed is cytometric analysis of cell size and heterogeneity of size as a potential biomarker used to asses gero‐suppressive agents and longevity. © 2014 International Society for Advancement of Cytometry
A high‐throughput LC‐MS/MS screen for GHRP in equine and human urine, featuring peptide derivatization for improved chromatography
Authors: Timms Mark , Hall Nikki , Levina Vita , Vine John , Steel Rohan
Published: February 2014

The growth hormone releasing peptides (GHRPs) hexarelin, ipamorelin, alexamorelin, GHRP‐1, GHRP‐2, GHRP‐4, GHRP‐5, and GHRP‐6 are all synthetic met‐enkephalin analogues that include unnatural D‐amino acids. They were designed specifically for their ability to stimulate growth hormone release and may serve as performance enhancing drugs. To regulate the use of these peptides within the horse racing industry and by human athletes, a method is presented for the extraction, derivatization, and detection of GHRPs from equine and human urine. This method takes advantage of a highly specific solid‐phase extraction combined with a novel derivatization method to improve the chromatography of basic peptides. The method was validated with respect to linearity, repeatability, intermediate precision, specificity, limits of detection, limits of confirmation, ion suppression, and stability. As proof of principle, all eight GHRPs or their metabolites could be detected in urine collected from rats after intravenous administration. Copyright © 2014 John Wiley & Sons, Ltd.
Mesodermal Fgf10b cooperates with other fibroblast growth factors during induction of otic and epibranchial placodes in zebrafish
Authors: Maulding Kirstin , Padanad Mahesh S. , Dong Jennifer , Riley Bruce B.
Published: February 2014

Background: Vertebrate otic and epibranchial placodes develop in close proximity in response to localized fibroblast growth factor (Fgf) signaling. Although less is known about epibranchial induction, the process of otic induction in highly conserved, with important roles for Fgf3 and Fgf8 reported in all species examined. Fgf10 is also critical for otic induction in mouse, but the only zebrafish ortholog examined to date, fgf10a, is not expressed early enough to play such a role. A second zebrafish ortholog, fgf10b, has not been previously examined. Results: We find that zebrafish fgf10b is expressed at tailbud stage in paraxial cephalic mesoderm beneath prospective epibranchial tissue, lateral to the developing otic placode. Knockdown of fgf10b does not affect initial otic induction but impairs subsequent accumulation of otic cells. Formation of epibranchial placodes and ganglia are also moderately impaired. Combinatorial disruption of fgf10b and fgf3 exacerbates the deficiency of otic cells and eliminates epibranchial induction entirely. Disruption of fgf10b and fgf24 also strongly reduces, but does not eliminate, epibranchial induction. Conclusions: fgf10b participates in a late phase of otic induction and, in combination with fgf3, is especially critical for epibranchial induction. Developmental Dynamics 243:1275–1285, 2014. © 2014 Wiley Periodicals, Inc.
Effect of the Mediterranean diet on heart failure biomarkers: a randomized sample from the PREDIMED trial
Authors: Fitó Montserrat , Estruch Ramón , Salas‐Salvadó Jordi , Martínez‐Gonzalez Miguel Angel , Arós Fernando , Vila Joan , Corella Dolores , Díaz Oscar , Sáez Guillermo , de la Torre Rafael , Mitjavila María‐Teresa , Muñoz Miguel Angel , Lamuela‐Raventós Rosa‐María , Ruiz‐Gutierrez Valentina , Fiol Miquel , Gómez‐Gracia Enrique , Lapetra José , Ros Emilio , Serra‐Majem Lluis , Covas María‐Isabel ,   on behalf of the PREDIMED Study Investigators
Published: February 2014

Aims

Scarce data are available on the effect of the traditional Mediterranean diet (TMD) on heart failure biomarkers. We assessed the effect of TMD on biomarkers related to heart failure in a high cardiovascular disease risk population.

Methods and Results

A total of 930 subjects at high cardiovascular risk (420 men and 510 women) were recruited in the framework of a multicentre, randomized, controlled, parallel‐group clinical trial directed at testing the efficacy of the TMD on the primary prevention of cardiovascular disease (The PREDIMED Study). Participants were assigned to a low‐fat diet (control, n = 310) or one of two TMDs [TMD + virgin olive oil (VOO) or TMD + nuts]. Depending on group assignment, participants received free provision of extra‐virgin olive oil, mixed nuts, or small non‐food gifts. After 1 year of intervention, both TMDs decreased plasma N‐terminal pro‐brain natriuretic peptide, with changes reaching significance vs. control group (P < 0.05). Oxidized low‐density lipoprotein decreased in both TMD groups (P < 0.05), the decrease in TMD + VOO group reaching significance vs. changes in control group (P = 0.003). Changes in lipoprotein(a) after TMD + VOO were less than those in the control group (P = 0.046) in which an increase (P = 0.035) was observed. No changes were observed in urinary albumin or albumin/creatinine ratio.

Conclusions

Individuals at high risk of cardiovascular disease (CVD) who improved their diet toward a TMD pattern reduced their N‐terminal pro‐brain natriuretic peptide compared with those assigned to a low‐fat diet. The same was found for in vivo oxidized low‐density lipoprotein and lipoprotein(a) plasma concentrations after the TMD + VOO diet. From our results TMD could be a useful tool to mitigate against risk factors for heart failure. From our results TMD could modify markers of heart failure towards a more protective mode.
CO Substitution Reactions of Diiron Complexes [{(μ‐SCH2)2X}Fe2(CO)6] and [{(μ‐SeCH2)2X}Fe2(CO)6] (X = O, CH2) with Ph2PCl/Me3NO to Give Ph2PCl‐, Ph2PNMe2‐, and Ph2PP(=O)Ph2‐Substituted Complexes Related to [FeFe] Hydrogenases
Authors: Song Li‐Cheng , Cao Meng , Du Zong‐Qiang , Feng Zhan‐Heng , Ma Zhen , Song Hai‐Bin
Published: February 2014

Diiron carbonyl complex [{(μ‐SCH2)2O}Fe2(CO)6] (A) reacted with Ph2PCl and Me3NO in MeCN at room temperature to give the expected and unexpected Ph2PCl‐, Ph2PNMe2‐, and Ph2PP(=O)Ph2‐substituted complexes [{(μ‐SCH2)2O}Fe2(CO)5L] [1, L = Ph2PCl; 2, L = Ph2PNMe2; 3, L = Ph2PP(=O)Ph2], whereas complex [{(μ‐SCH2)2CH2}Fe2(CO)6] (B) reacted with Ph2PCl and Me3NO under similar conditions to afford only the unexpected complexes [{(μ‐SCH2)2CH2}Fe2(CO)5L] [4, L = Ph2PNMe2; 5, L = Ph2PP(=O)Ph2]. Similarly, complex [{(μ‐SeCH2)2O}Fe2(CO)6] (C) reacted with Ph2PCl and Me3NO in MeCN at room temperature to give the unexpected complexes [{(μ‐SeCH2)2O}Fe2(CO)5L] [6, L = Ph2PNMe2; 7, L = Ph2PP(=O)Ph2], and the corresponding unexpected complexes [{(μ‐SeCH2)2CH2}Fe2(CO)5L] [8, L = Ph2PNMe2; 9, L = Ph2PP(=O)Ph2] were produced by the reaction of complex [{(μ‐SeCH2)2CH2}Fe2(CO)6] (D) with Ph2PCl and Me3NO under similar conditions. The structures of 1–9 were characterized by elemental analysis and spectroscopy, and for 1–5 and 7–9 by X‐ray crystallography. Possible pathways for the formation of the functionalized phosphine‐substituted complexes 1–9 have been suggested. Complexes 1–9 can be regarded as models for [FeFe] hydrogenases as their structures are similar to the active site of [FeFe] hydrogenases, and some have been found to be catalysts for proton reduction to hydrogen in the presence of HOAc.
A Novel L‐Cysteine Electrochemical Sensor Using Sulfonated Graphene‐poly(3,4‐Ethylenedioxythiophene) Composite Film Decorated with Gold Nanoparticles
Authors: Wang Xiaoqiang , Wen Yangping , Lu Limin , Xu Jingkun , Zhang Long , Yao Yuanyuan , He Haohua
Published: February 2014

By exploiting the electrostatic interaction between positively charged 3,4‐ethylenedioxythiophene cation radicals and negatively charged sulfonated graphene (SG) sheets, we prepared a poly(3,4‐ethylenedioxythiophene)‐sulfonated graphene (SG‐PEDOT) composite film by a one‐step electrochemical process. The composite was further decorated with gold nanoparticles (AuNPs) and employed as an electrode material for the detection of L‐cysteine (Cys). The SG‐PEDOT composite film is shown to provide a rough surface for the electrodeposition of AuNPs and to improve substrate accessibility and interaction with Cys. Moreover, the AuNPs‐decorated composite exhibits better electrocatalytic performance than that of a SG‐PEDOT composite only. Under optimum experimental conditions, the amperometric current of the sensor is linearly related to the concentration of Cys in the 0.1 to 382 µM range, and the detection limit is 0.02 µM (at S/N=3). The modified electrode displays favorable selectivity, good stability and high reproducibility. The method was successfully applied to the detection of Cys in spiked human urine.
Nitrite‐Selective Electrode Based On Cobalt(II) tert‐Butyl‐Salophen Ionophore
Authors: Néel Bastien , Ghahraman Asfhar Majid , Crespo Gastón A. , Pawlak Marcin , Dorokhin Denis , Bakker Eric
Published: February 2014

A series of polymeric nitrite‐selective electrodes containing a new lipophilic ionophore Co(II) tert‐butyl‐salophen is reported. The stability of Co(II) ionophores within a PVC‐based membrane was investigated by leaching experiments. Different membrane compositions were explored in order to reach the lowest possible limit of detection for a PVC‐based nitrite selective polymeric membrane electrode containing this ionophore. The optimal electrode showed a limit of detection of 2×10−6 M and exhibited four orders of magnitude of discrimination over nitrate, chloride and bromide. The electrodes were evaluated in undiluted human urine and attest to the robustness of the ionophore.
Mechanisms of chromosomal instability in melanoma
Authors: Kaufmann William K. , Carson Craig C. , Omolo Bernard , Filgo Adam J. , Sambade Maria J. , Simpson Dennis A. , Shields Janiel M. , Ibrahim Joseph G. , Thomas Nancy E.
Published: February 2014

A systems biology approach was applied to investigate the mechanisms of chromosomal instability in melanoma cell lines. Chromosomal instability was quantified using array comparative genomic hybridization to identify somatic copy number alterations (deletions and duplications). Primary human melanocytes displayed an average of 8.5 alterations per cell primarily representing known polymorphisms. Melanoma cell lines displayed 25 to 131 alterations per cell, with an average of 68, indicative of chromosomal instability. Copy number alterations included approximately equal numbers of deletions and duplications with greater numbers of hemizygous (−1,+1) alterations than homozygous (−2,+2). Melanoma oncogenes, such as BRAF and MITF, and tumor suppressor genes, such as CDKN2A/B and PTEN, were included in these alterations. Duplications and deletions were functional as there were significant correlations between DNA copy number and mRNA expression for these genes. Spectral karyotype analysis of three lines confirmed extensive chromosomal instability with polyploidy, aneuploidy, deletions, duplications, and chromosome rearrangements. Bioinformatic analysis identified a signature of gene expression that was correlated with chromosomal instability but this signature provided no clues to the mechanisms of instability. The signature failed to generate a significant (P = 0.105) prediction of melanoma progression in a separate dataset. Chromosomal instability was not correlated with elements of DNA damage response (DDR) such as radiosensitivity, nucleotide excision repair, expression of the DDR biomarkers γH2AX and P‐CHEK2, nor G1 or G2 checkpoint function. Chromosomal instability in melanoma cell lines appears to influence gene function but it is not simply explained by alterations in the system of DDR. Environ. Mol. Mutagen. 55:457–471, 2014. © 2014 Wiley Periodicals, Inc.
Epigenome‐wide DNA methylation changes with development of arsenic‐induced skin lesions in Bangladesh: A case–control follow‐up study
Authors: Seow Wei Jie , Kile Molly L. , Baccarelli Andrea A. , Pan Wen‐Chi , Byun Hyang‐Min , Mostofa Golam , Quamruzzaman Quazi , Rahman Mahmuder , Lin Xihong , Christiani David C.
Published: February 2014

Studies have found an association between aberrant DNA methylation and arsenic‐induced skin lesions. However, little is known about DNA methylation changes over time in people who develop arsenic‐induced skin lesions. We sought to investigate epigenome‐wide changes of DNA methylation in people who developed arsenic‐induced skin lesions in a 10‐year period. In 2009–2011, we conducted a follow‐up study of 900 skin lesion cases and 900 controls and identified 10 people who developed skin lesions since a baseline survey in 2001–2003. The 10 cases (“New Cases”) were matched with 10 controls who did not have skin lesions at baseline or follow‐up (“Persistent Controls”). Drinking water and blood samples were collected, and skin lesion was diagnosed by the same physician at both time points. We measured DNA methylation in blood using Infinium HumanMethylation450K BeadChip, followed by quantitative validation using pyrosequencing. Two‐sample t‐tests were used to compare changes in percent methylation between New Cases and Persistent Controls. Six CpG (cytosine‐phosphate‐guanine) sites with greatest changes of DNA methylation over time among New Cases were further validated with a correlation of 93% using pyrosequencing. One of the validated CpG site (cg03333116; change of %methylation was 13.2 in New Cases versus −0.09 in Persistent Controls; P < 0.001) belonged to the RHBDF1 gene, which was previously reported to be hypermethylated in arsenic‐exposed cases. We examined DNA methylation changes with the development of arsenic‐induced skin lesions over time but nothing was statistically significant given the small sample size of this exploratory study and the high dimensionality of data. Environ. Mol. Mutagen. 55:449–456, 2014. © 2014 Wiley Periodicals, Inc.
Mitochondrially targeted ZFNs for selective degradation of pathogenic mitochondrial genomes bearing large‐scale deletions or point mutations
Authors: Gammage Payam A , Rorbach Joanna , Vincent Anna I , Rebar Edward J , Minczuk Michal
Published: February 2014

We designed and engineered mitochondrially targeted obligate heterodimeric zinc finger nucleases (mtZFNs) for site‐specific elimination of pathogenic human mitochondrial DNA (mtDNA). We used mtZFNs to target and cleave mtDNA harbouring the m.8993T>G point mutation associated with neuropathy, ataxia, retinitis pigmentosa (NARP) and the “common deletion” (CD), a 4977‐bp repeat‐flanked deletion associated with adult‐onset chronic progressive external ophthalmoplegia and, less frequently, Kearns‐Sayre and Pearson's marrow pancreas syndromes. Expression of mtZFNs led to a reduction in mutant mtDNA haplotype load, and subsequent repopulation of wild‐type mtDNA restored mitochondrial respiratory function in a CD cybrid cell model. This study constitutes proof‐of‐principle that, through heteroplasmy manipulation, delivery of site‐specific nuclease activity to mitochondria can alleviate a severe biochemical phenotype in primary mitochondrial disease arising from deleted mtDNA species.
AMPed up to treat prostate cancer: novel AMPK activators emerge for cancer therapy
Authors: Schiewer Matthew J , Knudsen Karen E
Published: February 2014

Despite recent advances in the treatment for metastatic prostatic adenocarcinoma, clinical management of this tumor type remains a major challenge, and there is as of yet no durable cure for advanced disease. Developing pathways that could be co‐targeted alongside the androgen receptor or that would otherwise thwart the development of the CRPC is a current translational and clinical priority. In this issue, a new study by Zadra et al identifies the energy sensor AMPK (5′ AMP‐activated kinase) as a viable therapeutic target in prostate cancer.
Memory Versus Perception of Body Size in Patients with Anorexia Nervosa and Healthy Controls
Authors: Øverås Maria , Kapstad Hilde , Brunborg Cathrine , Landrø Nils Inge , Lask Bryan
Published: February 2014

The objective of this study was to compare body size estimation based on memory versus perception, in patients with anorexia nervosa (AN) and healthy controls, adjusting for possible confounders. Seventy‐one women (AN: 37, controls: 35), aged 14–29 years, were assessed with a computerized body size estimation morphing program. Information was gathered on depression, anxiety, time since last meal, weight and height. Results showed that patients overestimated their body size significantly more than controls, both in the memory and perception condition. Further, patients overestimated their body size significantly more when estimation was based on perception than memory. When controlling for anxiety, the difference between patients and controls no longer reached significance. None of the other confounders contributed significantly to the model. The results suggest that anxiety plays a role in overestimation of body size in AN. This finding might inform treatment, suggesting that more focus should be aimed at the underlying anxiety. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.
A simple method to determine mineralization of 14C-labeled compounds in soil
Authors: Myung Kyung , Madary Michael W. , Satchivi Norbert M.
Published: February 2014

Degradation of organic compounds in soil is often determined by measuring the decrease of the parent compound and analyzing the occurrence of its metabolites. However, determining carbon species as end products of parent compound dissipation requires using labeled materials that allow more accurate determination of the environmental fate of the compound of interest. The current conventional closed system widely used to monitor degradation of 14C-labeled compounds in soil is complex and expensive and requires a specialized apparatus and facility. In the present study, the authors describe a simple system that facilitates measurement of mineralization of 14C-labeled compounds applied to soil samples. In the system, soda lime pellets to trap mineralized 14C-carbon species, including carbon dioxide, were placed in a cup, which was then inserted above the treated soil sample in a tube. Mineralization of [14C]2,4-D applied to soil samples in the simple system was compared with that in the conventional system. The simple system provided an equivalent detection of 14C-carbon species mineralized from the parent compound. The results demonstrate that this cost- and space-effective simple system is suitable for examining degradation and mineralization of 14C-labeled compounds in soil and could potentially be used to investigate their mineralization in other biological matrices. Environ Toxicol Chem 2014;33:1303–1307. © 2014 SETAC
Bioavailability and bioaccumulation of sediment-bound polychlorinated biphenyls to carp
Authors: Gaillard Juliette , Banas Damien , Thomas Marielle , Fournier Agnès , Feidt Cyril
Published: February 2014

The relative bioavailability of sediment-bound polychlorinated biphenyls (PCBs 138, 153, and 180) from a local contaminated site was examined using an in vivo carp model. Surface sediment from the PCB-contaminated site and spiked canola oil containing equivalent masses of PCBs were respectively incorporated in the sediment-dosed diets and oil-dosed diets at 3 dose levels resulting in 6 experimental diets. Juvenile carps (n = 90) were divided in 18 tanks (5 fish × 6 treatments × 3 tanks). Fish were fed the control diet during the adaptation period (15 d). Next, 1 fish was sampled in each tank and muscle tissues were combined in control groups. During the exposure period (15 d), the remaining fish were fed with 1 of the 6 experimental diets. At the end of the experiment, fish were sampled and muscle tissues were combined for each tank. The PCBs were monitored in feed and fish muscle. For both the contaminated sediment and spiked canola oil groups, concentrations of PCBs 138, 153, and 180 in muscle linearly increased with concentrations in food, with similar intercepts and slopes. In the present study, the sediment-bound PCBs were as bioavailable as those spiked into canola oil and fed to carp in a standard diet. Environ Toxicol Chem 2014;33:1324–1330. © 2014 SETAC
Delimitating species in paleoanthropology
Authors: White Tim D.
Published: February 2014

Evolutionary biologists created a large twentieth‐century literature about delimiting biological species. Paleontologists contributed the unique complications of deep time. Toward century's end, one participant wrote: “In all probability more paper has been consumed on the questions of the nature and definition of the species than any other subject in evolutionary and systematic biology.”
The species in primatology
Authors: Groves Colin
Published: February 2014

Biologists of the late eighteenth and early nineteenth centuries all bandied about the term “species,” but very rarely actually said what they meant by it. Often, however, one can get inside their thinking by piecing together some of their remarks. One of the most nearly explicit‐appropriately, for the man who wrote a book called The Origin of Species – was Charles Darwin: “Practically, when a naturalist can unite two forms together by others having intermediate characters, he treats the one as a variety of the other… He later translated this into evolutionary terms: “Hereafter, we shall be compelled to acknowledge that the only distinction between species and well‐marked varieties is, that the latter are known, or believed, to be connected at the present day by intermediate gradations, whereas species were formerly thus connected”1:484‐5
A darwinian species definition and its implications
Authors: Jolly Clifford J.
Published: February 2014

A review of the vast literature on the epistemology and ontology of “species” is far beyond the capacity of both the writer and the length‐allotment of this essay, limiting it to a somewhat dogmatic presentation of personal opinions, few of them original. Also prohibited by the prescribed word limit is an account of species concepts considered but not adopted; in many cases, their omission does not do justice to their intellectual content.