bluuebunny/crossref_metadata_2025_split huggingface dataset:
From the Sequence to the Conformation of the Unabridged Transmembrane Domains TM1 and TM2 of the cASIC1a Ion Channel – A Parallel Tempering Approach
Authors: Pietra Francesco 
Published: March 2015

AbstractThis work was devised to unravel, along replica‐exchange molecular‐dynamics (REMD) simulations, the conformation in solution of the TM1 and TM2 transmembrane domains of the homotrimeric cASIC1a ion channel. This includes the head of TM1 and tail of TM2 that had previously defied X‐ray diffraction analysis in the crystal. The structure of the open‐channel complex of cASIC1a with psalmotoxin 1 (PcTx1) was chosen here as a basis, although, to make the simulations affordable, the procedure was limited to the missing portions, including a few adjacent α‐helical turns. The latter were held fixed during the simulations. Reassembling the whole subunit, by superimposition of the fixed portions, resulted in diving of both TM1 and TM2 as continuous α‐helices into the cytoplasm. At completion of this work, it appeared, from similar X‐ray diffraction studies, that TM2 for both the complex of cASIC1a with the coral snake MitTx toxin, and the isolated desensitized ion channel, is discontinuous, with the triad G443‐A444‐S445 taking an extended, belt‐like conformation. In this way, a filter ring against hydrated ions is formed by G443 in the trimer. Our REMD examination of this complex revealed a strong resistance by G443, and only that residue, to take dihedral‐angle values compatible with an α‐helical conformation. This suggests that the flexibility of glycine alone does not explain formation of the extended, belt‐like conformation of the triad G443‐A444‐S445. This also requires cooperation in the trimer.
Tools of the Trade: Investigations into Design Strategies of Small Molecules to Target Components in Alzheimer's Disease
Authors: Derrick Jeffrey S. , Lim Mi Hee 
Published: March 2015

AbstractThe growing prevalence of Alzheimer's disease (AD) has warranted the development of effective therapeutic methods. Current available drugs for AD (i.e., acetylcholinesterase (AChE) inhibitors and N‐methyl‐D‐aspartate (NMDA) receptor antagonists) have only offered brief symptomatic relief. Considering that the numbers affected by AD are projected to substantially rise, long‐term strategies are urgently needed. The multiple series of small molecules to combat AD have been expanded, with current methods taking aim at factors, such as misfolded protein accumulation, metal ion dyshomeostasis, and oxidative stress. This concept article focuses on describing the design of compounds to target various components of AD and underlining recent advances that have been made.
Acid‐Stable Peroxoniobophosphate Clusters To Make Patterned Films
Authors: Son Jung‐Ho , Park Deok‐Hie , Keszler Douglas A. , Casey William H. 
Published: March 2015

AbstractTwo new peroxoniobophosphate clusters were isolated as tetramethylammonium (TMA) salts having the stoichiometries: TMA5[HNb4P2O14(O2)4]⋅9 H2O and TMA3[H7Nb6P4O24(O2)6]⋅7 H2O. The former is stable over the pH range: 3<pH<12 and the latter is stable only below pH 3. These two molecules interconvert as a function of solution pH. The [H7Nb6P4O24(O2)6]3− cluster can be used to fabricate patterned niobium phosphate films by electron‐beam lithography after solution deposition.
Bioisosteric Matrices for Ligands of Serotonin Receptors
Authors: Warszycki Dawid , Mordalski Stefan , Staroń Jakub , Bojarski Andrzej J. 
Published: March 2015

AbstractThe concept of bioisosteric replacement matrices is applied to explore the chemical space of serotonin receptor ligands, aiming to determine the most efficient ways of manipulating the affinity for all 5‐HT receptor subtypes. Analysis of a collection of over 1 million bioisosteres of compounds with measured activity towards serotonin receptors revealed that an average of 31 % of the ligands for each target are mutual bioisosteres. In addition, the collected dataset allowed the development of bioisosteric matrices—qualitative and quantitative descriptions of the biological effects of each predefined type of bioisosteric substitution, providing favored paths of modifying the compounds. The concept exemplified here for serotonin receptor ligands can likely be more broadly applied to other target classes, thus representing a useful guide for medicinal chemists designing novel ligands.
The Predicted Ensemble of Low‐Energy Conformations of Human Somatostatin Receptor Subtype 5 and the Binding of Antagonists
Authors: Dong Sijia S. , Abrol Ravinder , Goddard William A. 
Published: March 2015

AbstractHuman somatostatin receptor subtype 5 (hSSTR5) regulates cell proliferation and hormone secretion. However, the identification of effective therapeutic small‐molecule ligands is impeded because experimental structures are not available for any SSTR subtypes. Here, we predict the ensemble of low‐energy 3D structures of hSSTR5 using a modified GPCR Ensemble of Structures in Membrane BiLayer Environment (GEnSeMBLE) complete sampling computational method. We find that this conformational ensemble displays most interhelical interactions conserved in class A G protein‐coupled receptors (GPCRs) plus seven additional interactions (e.g., Y2.43–D3.49, T3.38–S4.53, K5.64–Y3.51) likely conserved among SSTRs. We then predicted the binding sites for a series of five known antagonists, leading to predicted binding energies consistent with experimental results reported in the literature. Molecular dynamics (MD) simulation of 50 ns in explicit water and lipid retained the predicted ligand‐bound structure and formed new interaction patterns (e.g. R3.50–T6.34) consistent with the inactive μ‐opioid receptor X‐ray structure. We suggest more than six mutations for experimental validation of our prediction. The final predicted receptor conformations and antagonist binding sites provide valuable insights for designing new small‐molecule drugs targeting SSTRs.
Iodide‐Free Ionic Liquid with Dual Redox Couples for Dye‐Sensitized Solar Cells with High Open‐Circuit Voltage
Authors: Li Chun‐Ting , Lee Chuan‐Pei , Lee Chi‐Ta , Li Sie‐Rong , Sun Shih‐Sheng , Ho Kuo‐Chuan 
Published: March 2015

AbstractA novel ionic‐liquid mediator, 1‐butyl‐3‐{2‐oxo‐2‐[(2,2,6,6‐tetramethylpiperidin‐4‐yl)amino]ethyl}‐1H‐imidazol‐3‐ium selenocyanate (ITSeCN), has been successfully synthesized for dye‐sensitized solar cells (DSSCs). ITSeCN possesses dual redox channels, imidazolium‐functionalized 2,2,6,6‐tetramethylpiperidine N‐oxyl (TEMPO) and selenocyanate, which can serve as the cationic redox mediator and the anionic redox mediator, respectively. Therefore, ITSeCN has a favorable redox nature, which results in a more positive standard potential, larger diffusivity, and better kinetic heterogeneous rate constant than those of iodide. The DSSC with the ITSeCN electrolyte shows an efficiency of 8.38 % with a high open‐current voltage (VOC) of 854.3 mV, and this VOC value is about 150 mV higher than that for the iodide‐based DSSC. Moreover, different electrocatalytic materials were employed to trigger the redox reaction of ITSeCN. The ITSeCN‐based DSSC with the CoSe counter electrode achieved the best performance of 9.01 %, which suggested that transition‐metal compound‐type materials would be suitable for our newly synthesized ITSeCN mediator.
Bulky Monodentate Biphenylarsine Ligands: Synthesis and Evaluation of Their Structure Effects in the Palladium‐Catalyzed Heck Reaction
Authors: Quinteros Gisela J. , Uberman Paula M. , Martín Sandra E. 
Published: March 2015

AbstractBiphenyl‐based arsine ligands were prepared in two‐step fashion by Pd‐catalyzed arsination and microwave‐assisted Suzuki–Miyaura coupling, providing sterically demanding arsine ligands in overall isolated yields up to 82 % as air‐stable solids. Short reaction times were achieved with the assistance of microwave irradiation in the direct and simple described protocol for the synthesis of biarylarsine ligands. The activities of the biphenyl arsine ligands were explored in Pd‐catalyzed Heck coupling. As a general trend, the ligands with “blocked” ortho‐positions on the non‐arsine‐containing ring of the biphenyl backbone performed more efficiently in the coupling reaction. This catalytic system allowed several interesting stilbenes to be obtained in very good yields.
Neurobiological and Clinical Variables Associated with Alcohol Abuse in Bulimia Nervosa
Authors: Vaz‐Leal Francisco J. , Ramos‐Fuentes María I. , Rodríguez‐Santos Laura , Flores‐Mateos Isabel S. , Franco‐Zambrano Andrés , Rojo‐Moreno Luis , Beato‐Fernández Luis 
Published: March 2015

AbstractThe study was aimed at analysing the reciprocal relationships of several clinical and neurobiological items in order to predict alcohol misuse in patients with bulimia nervosa (BN). Seventy BN patients and 70 healthy controls were assessed for depression, impulsivity, borderline personality traits and self‐defeating behaviours using specific scales; serum cortisol and 24‐hour urinary excretion of serotonin and 5‐hydroxiindolacetic acid were also assessed. The study confirmed the implications of these clinical factors for alcohol misuse in BN patients, but the results suggested that depressive symptoms and hypercortisolism could lie behind these relationships. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.
Prioritization of pharmaceuticals for potential environmental hazard through leveraging a large-scale mammalian pharmacological dataset
Authors: Berninger Jason P. , LaLone Carlie A. , Villeneuve Daniel L. , Ankley Gerald T. 
Published: March 2015

Abstract

The potential for pharmaceuticals in the environment to cause adverse ecological effects is of increasing concern. Given the thousands of active pharmaceutical ingredients (APIs) that can enter the aquatic environment through human and/or animal (e.g., livestock) waste, a current challenge in aquatic toxicology is identifying those that pose the greatest risk. Because empirical toxicity information for aquatic species is generally lacking for pharmaceuticals, an important data source for prioritization is that generated during the mammalian drug development process. Applying concepts of species read-across, mammalian pharmacokinetic data were used to systematically prioritize APIs by estimating their potential to cause adverse biological consequences to aquatic organisms, using fish as an example. Mammalian absorption, distribution, metabolism, and excretion (ADME) data (e.g., peak plasma concentration, apparent volume of distribution, clearance rate, and half-life) were collected and curated, creating the Mammalian Pharmacokinetic Prioritization For Aquatic Species Targeting (MaPPFAST) database representing 1070 APIs. From these data, a probabilistic model and scoring system were developed and evaluated. Individual APIs and therapeutic classes were ranked based on clearly defined read-across assumptions for translating mammalian-derived ADME parameters to estimate potential hazard in fish (i.e., greatest predicted hazard associated with lowest mammalian peak plasma concentrations, total clearance and highest volume of distribution, half-life). It is anticipated that the MaPPFAST database and the associated API prioritization approach will help guide research and/or inform ecological risk assessment. Environ Toxicol Chem 2016;35:1007–1020. Published 2015 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America.
Hydra viridissima (green Hydra) rapidly recovers from multiple magnesium pulse exposures
Authors: Prouse Andrea E. , Hogan Alicia C. , Harford Andrew J. , van Dam Rick A. , Nugegoda Dayanthi 
Published: March 2015

Abstract

The time taken for organisms to recover from a pulsed toxicant exposure is an important consideration when water quality guidelines are applied to intermittent events in the environment. Organisms may appear to have recovered by standard toxicity testing methods but could carry residual toxicant or damage that may make them more sensitive to subsequent pulses. Such cumulative effects may render guidelines underprotective. The present study evaluated recovery of the freshwater cnidarian Hydra viridissima following multiple pulse exposure to magnesium (Mg). The H. viridissima were exposed to 4-h pulses of 790 mg/L and 1100 mg/L separated by 2-h, 10-h, 18-h, 24-h, 48-h, and 72-h recovery periods. Twenty-four-hour pulses of 570 mg/L, 910 mg/L, and 940 mg/L were separated by 24-h, 96-h, and 168-h recovery periods. All treatments showed similar or reduced sensitivity to the second pulse when compared with the single pulse, indicating that full recovery occurred prior to a second pulse-exposure. Five variations of equivalent time-weighted average concentrations were used to compare sensitivity of Hydra with various pulse scenarios. The sensitivity of the organisms to the multiple pulses was significantly lower than the time-weighted average continuous exposure response in 3 of the 4 scenarios tested, indicating that the Hydra benefited from interpulse recovery periods. The findings will be utilized alongside those from other species to inform the use of a site-specific, duration-based water quality guideline for Mg, and they provide an example of the use of empirical data in the regulation of toxicant pulses in the environment. Environ Toxicol Chem 2015;34:1734–1743. © 2015 Commonwealth of Australia
Cadmium sulfide quantum dots induce oxidative stress and behavioral impairments in the marine clam Scrobicularia plana
Authors: Buffet Pierre-Emmanuel , Zalouk-Vergnoux Aurore , Poirier Laurence , Lopes Christelle , Risso-de-Faverney Christine , Guibbolini Marielle , Gilliland Douglas , Perrein-Ettajani Hanane , Valsami-Jones Eugenia , Mouneyrac Catherine 
Published: March 2015

Abstract

Cadmium sulfide (CdS) quantum dots have a number of current applications in electronics and solar cells and significant future potential in medicine. The aim of the present study was to examine the toxic effects of CdS quantum dots on the marine clam Scrobicularia plana exposed for 14 d to these nanomaterials (10 µg Cd L–1) in natural seawater and to compare them with soluble Cd. Measurement of labile Cd released from CdS quantum dots showed that 52% of CdS quantum dots remained in the nanoparticulate form. Clams accumulated the same levels of Cd regardless of the form in which it was delivered (soluble Cd vs CdS quantum dots). However, significant changes in biochemical responses were observed in clams exposed to CdS quantum dots compared with soluble Cd. Increased activities of catalase and glutathione-S-transferase were significantly higher in clams exposed in seawater to Cd as the nanoparticulate versus the soluble form, suggesting a specific nano effect. The behavior of S. plana in sediment showed impairments of foot movements only in the case of exposure to CdS quantum dots. The results show that oxidative stress and behavior biomarkers are sensitive predictors of CdS quantum dots toxicity in S. plana. Such responses, appearing well before changes might occur at the population level, demonstrate the usefulness of this model species and type of biomarker in the assessment of nanoparticle contamination in estuarine ecosystems. Environ Toxicol Chem 2015;34:1659–1664. © 2015 SETAC
Linking the chemical speciation of cerium to its bioavailability in water for a freshwater alga
Authors: El-Akl Philippe , Smith Scott , Wilkinson Kevin J. 
Published: March 2015

Abstract

Over the past decade, researchers have begun to use metals of the lanthanide family for numerous applications, including liquid crystal display (LCD) screens, optical fibers, and laser technology. Unfortunately, little is presently known about their bioavailability or the mechanisms by which they might cause toxicity. The present study focuses on cerium (Ce), one of the most widely used lanthanides, and on validating the biotic ligand model as a means to predict Ce bioaccumulation. Short-term exposures to Ce were performed using the unicellular alga Chlamydomonas reinhardtii, to better relate Ce bioavailability to its chemical speciation in solution. Maximum uptake fluxes (Jmax) and affinity constants for the binding of Ce to the biological uptake sites (KS) were established at pH 5.0 and pH 7.0. An apparent affinity constant of 1.8 × 107 M–1 was observed at pH 5.0, with a larger value obtained at pH 7.0 (6 × 107 M–1), albeit under conditions where equilibrium could not be confirmed. By evaluating Ce speciation using centrifugal ultrafiltration and single-particle inductively coupled plasma spectrometry, it could be concluded that very little (∼30%) Ce was truly dissolved at pH 7.0, with the majority of the metal being present in colloidal species. Speciation was also monitored by fluorescence to evaluate Ce complexation by natural organic matter (NOM). The presence of NOM decreased Ce bioaccumulation in line with free Ce concentrations. Finally, competition with calcium for the metal uptake sites was shown to result in a decrease in Ce uptake by C. reinhardtii. Environ Toxicol Chem 2015;34:1711–1719. © 2015 SETAC
Immediate memory for “when, where and what”: Short‐delay retrieval using dynamic naturalistic material
Authors: Kwok Sze Chai , Macaluso Emiliano 
Published: March 2015

AbstractWe investigated the neural correlates supporting three kinds of memory judgments after very short delays using naturalistic material. In two functional magnetic resonance imaging (fMRI) experiments, subjects watched short movie clips, and after a short retention (1.5–2.5 s), made mnemonic judgments about specific aspects of the clips. In Experiment 1, subjects were presented with two scenes and required to either choose the scene that happened earlier in the clip (“scene‐chronology”), or with a correct spatial arrangement (“scene‐layout”), or that had been shown (“scene‐recognition”). To segregate activity specific to seen versus unseen stimuli, in Experiment 2 only one probe image was presented (either target or foil). Across the two experiments, we replicated three patterns underlying the three specific forms of memory judgment. The precuneus was activated during temporal‐order retrieval, the superior parietal cortex was activated bilaterally for spatial‐related configuration judgments, whereas the medial frontal cortex during scene recognition. Conjunction analyses with a previous study that used analogous retrieval tasks, but a much longer delay (>1 day), demonstrated that this dissociation pattern is independent of retention delay. We conclude that analogous brain regions mediate task‐specific retrieval across vastly different delays, consistent with the proposal of scale‐invariance in episodic memory retrieval.Hum Brain Mapp 36:2495–2513, 2015. ©2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
Identification of Five New Minor Constituents from the Whole Plant of Amischotolype hispida
Authors: Chang Chun‐Wei , Chang Hsun‐Shuo , Cheng Ming‐Jen , Peng Chien‐Fang , Chen Ih‐Sheng 
Published: March 2015

AbstractBioassay‐guided fractionation of the active AcOEt‐soluble layer from the whole plant of Amischotolype hispida resulted in the isolation of four new compounds, i.e., amisbenzoic acid (1), one butenolide derivative, amisnolide (2), one chlorin analog, amisphytin (3), one lignan, amislignol (4), and one metabolite isolated for the first time from nature, (−)‐glaberide I (5), along with 20 known compounds, 6–25. Their structures were elucidated on the basis of UV, IR, 1D‐ and 2D‐NMR (1H,1H‐COSY, DEPT, HSQC, HMBC), as well as HR‐ESI‐MS, analyses. Among these isolates, palmitic acid (13) showed an antimycobacterial activity with an MIC value of 20.0 μg/ml against Mycobacterium tuberculosis H37Rv.
Synthesis of New Pyrano[2′,3′: 5,6]chromeno[4,3‐b]quinolin‐4‐ones via Aza‐DielsAlder Reaction
Authors: Kumar Bejjanki Naveen , Venkatesham Akkaladevi , Nagaiah Kommu , Babu Nanubolu Jagadeesh 
Published: March 2015

AbstractNew pyrano[2′,3′: 5,6]chromeno[4,3‐b]quinolin‐4‐ones have been synthesized by intramolecular aza‐DielsAlder reaction of the azadienes generated in situ from aryl amines and 8‐formyl‐7‐(prop‐2‐ynyl)2,3‐disubstituted chromones using CuFe2O4 nanoparticles as a catalyst in DMSO at 80–90° in good‐to‐excellent yields. Particularly valuable features of this methodology include simple implementation, inexpensive and reusable catalyst, and good yields. The structures were established by spectroscopic data and further confirmed by X‐ray diffraction analysis of one of the products.
A Facile Synthesis of 1‐Substituted 3‐Alkoxy‐1H‐isoindoles Based on the Reaction of 2‐(Dialkoxymethyl)phenyllithiums with Nitriles, Followed by Acid‐Catalyzed Cyclization
Authors: Kuroda Minami , Kobayashi Kazuhiro 
Published: March 2015

AbstractA two‐step synthesis of 1‐substituted 3‐alkoxy‐1H‐isoindoles 4 has been developed. Thus, the reaction of 2‐(dialkoxymethyl)phenyllithium compounds, which are easily generated in situ by Br/Li exchange between 1‐bromo‐2‐(dialkoxymethyl)benzenes 1 and BuLi in THF at −78°, with nitriles afforded [2‐(dialkoxymethyl)phenyl]methanimines 2, which were treated with a catalytic amount of TsOH⋅H2O in refluxing CHCl3 to give the desired products in reasonable yields. Similarly, 3‐aryl‐1‐ethoxy‐1‐methyl‐1H‐isoindoles 7 have been prepared starting from 1‐bromo‐2‐(1,1‐diethoxyethyl)benzenes 5.
Effects of Reclaimed Water on the Growth and Fruit Quality of Cucumber
Authors: Chen Feng‐Wen , Liu Chen‐Wuing 
Published: March 2015

AbstractThe purpose of this study was to evaluate the feasibility of using reclaimed water for cucumber irrigation. The experiment was conducted using raw canal water, and water reclaimed from treated wastewater using a natural recycling treatment system. The raw water quality met the Irrigation Water Quality Standards of Taiwan. The water quality of reclaimed water was treated within the ranges of DO: 3.9–8.4 (mg l−1); pH: 6.5–7.8; EC: 206–587 (µs cm−1, 25 °C); SS: 0.1–11.8 (mg l−1); NH4‐N: 0–18.16 (mg l−1) and BOD: 0.1–1.8 (mg l−1). The experimental period for cucumber growth was 75 days. Rg was defined as the different multiple of plant growth and used to estimate the effects of irrigation water quality. Furthermore, yield, weight, length, and diameter of cucumbers were used to quantify the influence of irrigation water quality on cucumber quality. Result shows that Rg was within the range (1.003–1.311). The heights of cucumbers grown using reclaimed water were longer than those grown using raw water. Comparing the yield, weight, length, and diameter of cucumbers irrigated by reclaimed water (RW) and by raw water (IW), the percentages of RW/IW were respectively 154, 96, 95.5 and 101%. Based on the results, this study concludes that using reclaimed water for cucumber irrigation is feasible. Copyright © 2015 John Wiley & Sons, Ltd.