bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Type II Fatty Acid Biosynthesis (FAS II) Inhibitors as Multistage Antimalarial Agents
Authors: Schrader Florian C. , Glinca Serghei , Sattler Julia M. , Dahse Hans‐Martin , Afanador Gustavo A. , Prigge Sean T. , Lanzer Michael , Mueller Ann‐Kristin , Klebe Gerhard , Schlitzer Martin 
Published: January 2013

AbstractMalaria is a potentially fatal disease caused by Plasmodium parasites and poses a major medical risk in large parts of the world. The development of new, affordable antimalarial drugs is of vital importance as there are increasing reports of resistance to the currently available therapeutics. In addition, most of the current drugs used for chemoprophylaxis merely act on parasites already replicating in the blood. At this point, a patient might already be suffering from the symptoms associated with the disease and could additionally be infectious to an Anopheles mosquito. These insects act as a vector, subsequently spreading the disease to other humans. In order to cure not only malaria but prevent transmission as well, a drug must target both the blood‐ and pre‐erythrocytic liver stages of the parasite. P. falciparum (Pf) enoyl acyl carrier protein (ACP) reductase (ENR) is a key enzyme of plasmodial type II fatty acid biosynthesis (FAS II). It has been shown to be essential for liver‐stage development of Plasmodium berghei and is therefore qualified as a target for true causal chemoprophylaxis. Using virtual screening based on two crystal structures of PfENR, we identified a structurally novel class of FAS inhibitors. Subsequent chemical optimization yielded two compounds that are effective against multiple stages of the malaria parasite. These two most promising derivatives were found to inhibit blood‐stage parasite growth with IC50 values of 1.7 and 3.0 μM and lead to a more prominent developmental attenuation of liver‐stage parasites than the gold‐standard drug, primaquine.
A “Clickable” MTX Reagent as a Practical Tool for Profiling Small‐Molecule–Intracellular Target Interactions via MASPIT
Authors: Risseeuw Martijn D. P. , De Clercq Dries J. H. , Lievens Sam , Hillaert Ulrik , Sinnaeve Davy , Van den Broeck Freya , Martins José C. , Tavernier Jan , Van Calenbergh Serge 
Published: January 2013

AbstractWe present a scalable synthesis of a versatile MTX reagent with an azide ligation handle that allows rapid γ‐selective conjugation to yield MTX fusion compounds (MFCs) appropriate for MASPIT, a three‐hybrid system that enables the identification of mammalian cytosolic proteins that interact with a small molecule of interest. We selected three structurally diverse pharmacologically active compounds (tamoxifen, reversine, and FK506) as model baits. After acetylene functionalization of these baits, MFCs were synthesized via a CuAAC reaction, demonstrating the general applicability of the MTX reagent. In analytical mode, MASPIT was able to give concentration‐dependent reporter signals for the established target proteins. Furthermore, we demonstrate that the sensitivity obtained with the new MTX reagent was significantly stronger than that of a previously used non‐regiomeric conjugate mixture. Finally, the FK506 MFC was explored in a cellular array screen for targets of FK506. Out of a pilot collection of nearly 2000 full‐length human ORF preys, FKBP12, the established target of FK506, emerged as the prey protein that gave the highest increase in luciferase activity. This indicates that our newly developed synthetic strategy for the straightforward generation of MFCs is a promising asset to uncover new intracellular targets using MASPIT cellular array screening.
Electrochemically Induced Release of a Luminescent Probe from a Rhenium‐Containing Metallopolymer
Authors: Valenti Giovanni , O'Reilly Emmet J , McNally Andrea , Keyes Tia E. , Marcaccio Massimo , Paolucci Francesco , Forster Robert J. 
Published: January 2013

AbstractInvited for this month′s cover is the group of Prof. Francesco Paolucci and the group of Prof. Robert Forster and Prof. Tia E. Keyes. The cover picture shows release of the luminescent rhenium coordination complex in solution.
Individual differences in fear potentiated startle in behaviorally inhibited children
Authors: Barker Tyson V. , Reeb‐Sutherland Bethany C. , Fox Nathan A. 
Published: January 2013

AbstractBehavioral inhibition (BI) is a temperament characterized during early childhood by increased fearfulness to novelty, social reticence to unfamiliar peers, and heightened risk for the development of anxiety. Heightened startle responses to safety cues have been found among behaviorally inhibited adolescents who have an anxiety disorder suggesting that this measure may serve as a biomarker for the development of anxiety amongst this risk population. However, it is unknown if these aberrant startle patterns emerge prior to the manifestation of anxiety in this temperament group. The current study examined potentiated startle in 7‐year‐old children characterized with BI early in life. High behaviorally inhibited children displayed increased startle magnitude to safety cues, particularly during the first half of the task, and faster startle responses compared to low behaviorally inhibited children. These findings suggest that aberrant startle responses are apparent in behaviorally inhibited children during early childhood prior to the onset of a disorder and may serve as a possible endophenotype for the development of anxiety. © 2013 Wiley Periodicals, Inc. Dev Psychobiol 56: 133–141, 2014.
Binge ethanol intoxication heightens subsequent ethanol intake in adolescent, but not adult, rats
Authors: Fabio María Carolina , Nizhnikov Michael E. , Spear Norman E. , Pautassi Ricardo Marcos 
Published: January 2013

AbstractA question still to be answered is whether ethanol initiation has a greater effect on ethanol consumption if it occurs during adolescence than in adulthood. This study assessed the effect of ethanol initiation during adolescence or adulthood on voluntary ethanol consumption when animals were still within the same age range. Adolescent or adult rats were given 5, 2, or 0 ethanol exposures. The animals were tested for ethanol consumption through two‐bottle choice tests, before undergoing a 1‐week deprivation. A two‐bottle assessment was conducted after the deprivation. Adolescents, but not adults, given two ethanol administrations during initiation exhibited significantly higher ethanol intake during the pre‐deprivation period. These adolescents also exhibited a threefold increase in ethanol intake after 7 days of drug withdrawal, when compared with controls. These findings suggest that very brief experience with binge ethanol intoxication in adolescence, but not in adulthood, impacts later predisposition to drink. © 2013 Wiley Periodicals, Inc. © 2013 Wiley Periodicals, Inc. Dev Psychobiol 56: 574–583, 2014.
Simplified analysis techniques for VLF wave propagation in the earth–ionosphere waveguide
Authors: Itoh Hitoshi , Ando Yoshiaki , Hayakawa Masashi 
Published: January 2013

AbstractVLF (very low frequency; 3 to 30 kHz) wave propagation in the earth–ionosphere waveguide can be simply analyzed by the method developed in this paper. The finite‐diﬀerence time‐domain (FDTD) method is used with a conductivity tensor to model the ionosphere, and the applicability is limited to monotonic cases. The proposed method is compared with the wideband method, and it is concluded that the newly developed method can be used as a VLF wave simulator without errors. Conformal FDTD is also introduced to allow for the curvature of the earth's surface, and we have clarified the diﬀerence between two‐dimensional modeling in Cartesian coordinates and cylindrical coordinates. © 2013 Wiley Periodicals, Inc. Electr Eng Jpn, 183(1): 25–31, 2013; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/eej.22302
Application of Different Zeolites for Improvement of the Characteristics of a pH‐FET Biosensor Based on Immobilized Urease
Authors: Soldatkin O. O. , Kucherenko I. S. , Shelyakina M. K. , Soy E. , Kirdeciler K. , Öztürk S. , Jaffrezic‐Renault N. , Akata B. , Dzyadevych S. V. , Soldatkin A. P. 
Published: January 2013

AbstractDifferent modifications of the zeolites Na+‐Beta and LTA were applied for improving the working characteristics of a urea biosensor. The bioselective membrane of the biosensor was based on urease and different zeolites co‐immobilized with bovine serum albumin on the surface of a pH‐FET. It was shown that the biosensors modified with the zeolites H+‐Beta30 and H+‐Beta50 are characterized by increased sensitivity to urea. The influence of the zeolite concentration on the sensitivity of the biosensors was studied. The optimal concentration of the zeolites H+‐Beta30 and H+‐Beta50 in the bioselective membrane was 15 %. Different variants of co‐immobilization of urease and zeolite H+‐Beta30 were studied and the optimal method was selected. Thus, a general conclusion is that the urea biosensor sensitivity can be improved using zeolite H+‐Beta30 for urease immobilization in the bioselective membrane.
Season of Birth Bias and Bulimia Nervosa—Results from a Multi‐centre Collaboration
Authors: Winje Eirin , Torgalsbøen Anne‐Kari , Brunborg Cathrine , Lask Bryan 
Published: January 2013

AbstractBackgroundSeason of birth bias has been observed for people with a number of disorders, including women with bulimia nervosa. However, inconsistent results and methodological weaknesses render previous conclusions about such bias uncertain. With an enhanced methodology, this study aims to test whether there is a season of birth bias for women with bulimia nervosa.MethodWomen with bulimia nervosa at five secondary and tertiary services in Norway, born between 1966 and 1988 (n = 549), were compared with women in the general population in a chi‐square test for contingency tables, with known population parameters testing monthly deviations.ResultsThere was no statistically significant association between month of birth and the distribution of births in the two groups (Cramer's V = .09).ConclusionThere appears not to be any season of birth bias in women with bulimia nervosa in Norway. Copyright © 2013 John Wiley & Sons, Ltd and Eating Disorders Association.
Lipase: A potential biocatalyst for the synthesis of valuable flavour and fragrance ester compounds
Authors: Dhake Kishor P. , Thakare Dinesh D. , Bhanage Bhalchandra M. 
Published: January 2013

ABSTRACTBiocatalysis has attracted special attention for the synthesis of industrially valuable ester compounds. This review focuses mainly on lipases obtained from different sources (commercially available or newly isolated) as biocatalysts for the synthesis of flavour and fragrance esters in solvent‐free as well as in non‐aqueous reaction media (i.e. organic and neoteric solvents). Neoteric solvents such as ionic liquids and supercritical fluids are greener and environmentally benign; their use in lipase‐catalysed ester synthesis is reviewed. The impact of an immobilization strategy to achieve higher yields (up to 99%) is discussed. The review also highlights the kinetic resolution of some important flavour/fragrance compounds synthesized using several chemo‐enzymatic strategies. Copyright © 2013 John Wiley & Sons, Ltd.
Olfactory ensheathing cells: The primary innate immunocytes in the olfactory pathway to engulf apoptotic olfactory nerve debris
Authors: Su Zhida , Chen Jingjing , Qiu Yang , Yuan Yimin , Zhu Feng , Zhu Yanling , Liu Xiujie , Pu Yingyan , He Cheng 
Published: January 2013

AbstractThe olfactory system is an unusual tissue in which olfactory receptor neurons (ORNs) are continuously replaced throughout the life of mammals. Clearance of the apoptotic ORNs corpses is a fundamental process serving important functions in the regulation of olfactory nerve turnover and regeneration. However, little is known about the underlying mechanisms. Olfactory ensheathing cells (OECs) are a unique type of glial cells that wrap olfactory axons and support their continual regeneration from the olfactory epithelium to the bulb. In the present study, OECs were identified to exist in two different states, resting and reactive, in which resting OECs could be activated by LPS stimulation and functioned as phagocytes for cleaning apoptotic ORNs corpses. Confocal analysis revealed that dead ORNs debris were engulfed by OECs and co‐localized with lysosome associated membrane protein 1. Moreover, phosphatidylserine (PS) receptor was identified to express on OECs, which allowed OECs to recognize apoptotic ORNs by binding to PS. Importantly, engulfment of olfactory nerve debris by OECs was found in olfactory mucosa under normal turnover and was significantly increased in the animal model of olfactory bulbectomy, while little phagocytosis by Iba‐1‐positive microglia/macrophages was observed. Together, these results implicate OEC as a primary innate immunocyte in the olfactory pathway, and suggest a cellular and molecular mechanism by which ORNs corpses are removed during olfactory nerve turnover and regeneration. © 2013 Wiley Periodicals, Inc.
Astrocytes are a neural target of morphine action via glucocorticoid receptor‐dependent signaling
Authors: Slezak Michal , Korostynski Michal , Gieryk Agnieszka , Golda Slawomir , Dzbek Jaroslaw , Piechota Marcin , Wlazlo Eliza , Bilecki Wiktor , Przewlocki Ryszard 
Published: January 2013

AbstractChronic opioid use leads to the structural reorganization of neuronal networks, involving genetic reprogramming in neurons and glial cells. Our previous in vivo studies have revealed that a significant fraction of the morphine‐induced alterations to the striatal transcriptome included glucocorticoid (GC) receptor (GR)‐dependent genes. Additional analyses suggested glial cells to be the locus of these changes. In the current study, we aimed to differentiate the direct transcriptional effects of morphine and a GR agonist on primary striatal neurons and astrocytes. Whole‐genome transcriptional profiling revealed that while morphine had no significant effect on gene expression in both cell types, dexamethasone significantly altered the transcriptional profile in astrocytes but not neurons. We obtained a complete dataset of genes undergoing the regulation, which includes genes related to glucose metabolism (Pdk4), circadian activity (Per1) and cell differentiation (Sox2). There was also an overlap between morphine‐induced transcripts in striatum and GR‐dependent transcripts in cultured astrocytes. We further analyzed the regulation of expression of one gene belonging to both groups, serum and GC regulated kinase 1 (Sgk1). We identified two transcriptional variants of Sgk1 that displayed selective GR‐dependent upregulation in cultured astrocytes but not neurons. Moreover, these variants were the only two that were found to be upregulated in vivo by morphine in a GR‐dependent fashion. Our data suggest that the morphine‐induced, GR‐dependent component of transcriptome alterations in the striatum is confined to astrocytes. Identification of this mechanism opens new directions for research on the role of astrocytes in the central effects of opioids. © 2013 Wiley Periodicals, Inc.
FETAL HEALTH SHOCKS AND EARLY INEQUALITIES IN HEALTH CAPITAL ACCUMULATION
Authors: Wehby George L. , Nyarko Kwame A. , Lopez‐Camelo Jorge S. 
Published: January 2013

AbstractSeveral studies report socioeconomic inequalities in child health and consequences of early disease. However, not much is known about inequalities in health capital accumulation in the womb in response to fetal health shocks, which is essential for finding the earliest sensitive periods for interventions to reduce inequalities. We identify inequalities in birth weight accumulation as a result of fetal health shocks from the occurrence of one of the most common birth defects, oral clefts, within the first 9 weeks of pregnancy, using quantile regression and two datasets from South America and the USA. Infants born at lower birth weight quantiles are significantly more adversely affected by the health shock compared with those born at higher birth weight quantiles, with overall comparable results between the South American and US samples. These results suggest that fetal health shocks increase child health disparities by widening the spread of the birth weight distribution and that health inequalities begin in the womb, requiring interventions before pregnancy. Copyright © 2013 John Wiley & Sons, Ltd.
PRICE CONTROLS FOR MEDICAL INNOVATIONS IN A LIFE CYCLE PERSPECTIVE
Authors: Sorek Gilad 
Published: January 2013

ABSTRACTWe study the market for new medical technologies from a life cycle perspective, incorporating the fact that healthcare utilization is biased towards old age. Contrary to conventional wisdom, we find that price controls on medical innovations can expand investment in medical R&D and results in Pareto superior social outcomes, a consequence of the price controls' ability to increase saving. Importantly, this finding occurs only when the price cap regime is extensive: selective regulation on few technologies – such as pharmaceuticals alone – have the conventional negative effect on innovation. Copyright © 2013 John Wiley & Sons, Ltd.
Regioselective [3+3] Cyclization of 1,3‐Bis(silyloxy)buta‐1,3‐dienes with 1,1,1‐Trifluoro‐4‐(silyloxy)alk‐3‐en‐2‐ones: New and Convenient Synthesis of Functionalized 5‐Alkyl‐3‐(trifluoromethyl)phenols
Authors: Büttner Stefan , Bunescu Alina , Reimann Sebastian , Tam Dang T. H. , Pundt Thomas , Klassen Renske , Schmidt Andreas , Kelzhanova Nazken K. , Abilov Zharylkasyn A. , Ghochikyan Tariel V. , Saghiyan Ashot S. , Villinger Alexander , Reinke Helmut , Spannenberg Anke , Langer Peter 
Published: January 2013

AbstractFunctionalized 5‐alkyl‐3‐(trifluoromethyl)phenols were prepared by formal [3+3] cyclization of 1,3‐bis(silyloxy)buta‐1,3‐dienes with 1,1,1‐trifluoro‐4‐(silyloxy)alk‐3‐en‐2‐ones derived from 1,1,1‐trifluoroalkane‐2,4‐diones. The latter were prepared by condensation of the dianion of 1,1,1‐trifluoropentane‐2,4‐dione with alkyl halides.
Synthesis of 4‐Aryl‐4,6‐dihydropyrimido[4,5‐d]pyridazine‐2,5(1H,3H)‐diones from Biginelli Compounds
Authors: Patra Gopal Chandra , Bhunia Sankar Chandra , Roy Monoj Kumar , Pal Sudhir Chandra 
Published: January 2013

AbstractBiginelli compounds 1 were first brominated at MeC(6) with 2,4,4,6‐tetrabromocyclohex‐2,5‐dien‐1‐one to give Br2CHC(6) derivatives 2. The hydrolysis of the 6‐(dibromomethyl) group of 2c to give the 6‐formyl derivative 3c in the presence of an expensive Ag salt followed by reaction with N2H4⋅H2O yielded tetrahydropyrimido[4,5‐d]pyridazine‐2,5(1H,3H)‐dione (4c; Scheme 1). However, treatment of the 6‐(dibromomethyl) derivatives 2 directly with N2H4⋅H2O led to the fused heterocycles 4 in better overall yield (Schemes 1 and 2; Table).
Three‐Step Synthesis of 3‐Aryl‐2‐sulfanylthieno[2,3‐b]‐, ‐[2,3‐c]‐, or ‐[3,2‐c]pyridines from the Corresponding Aryl(halopyridinyl)methanones
Authors: Kobayashi Kazuhiro , Suzuki Teruhiko , Egara Yuko 
Published: January 2013

AbstractA convenient three‐step procedure for the synthesis of three types of 3‐aryl‐2‐sulfanylthienopyridines 4, 8, and 12 has been developed. The first step of the synthesis of thieno[2,3‐b]pyridine derivatives 4 is the replacement of the halo with a (sulfanylmethyl)sulfanyl group in aryl(2‐halopyridin‐3‐yl)methanones 1 by successive treatment with Na2S⋅9 H2O and chloromethyl sulfides to give aryl{2‐[(sulfanylmethyl)sulfanyl]pyridin‐3‐yl}methanones 2. In the second step, these were treated with LDA (LiNiPr2) to give 3‐aryl‐2,3‐dihydro‐2‐sulfanylthieno[2,3‐b]pyridin‐3‐ols 3, which were dehydrated in the last step with SOCl2 in the presence of pyridine to give the desired products. Similarly, thieno[2,3‐c]pyridine and thieno[3,2‐c]pyridine derivatives, 8 and 12, respectively, can be prepared from aryl(3‐chloropyridin‐4‐yl)methanones 5 and aryl(4‐chloropyridin‐3‐yl)methanones 9, respectively.
Five New Cycloartane‐Type Triterpenoid Saponins from Nervilia fordii
Authors: Wei Liu‐Bin , Yuan Hong‐E , Chen Jin‐Man , Wang Qing‐Qing , Wang Hui , Ye Wen‐Cai , Zhou Guang‐Xiong 
Published: January 2013

AbstractFive new cycloartane glycosides, nervisides D–H (1–5), were isolated from the AcOEt‐ and H2O‐soluble portions of the 90% EtOH extract of the aerial part of the plant Nervilia fordii. The structures of the isolated glycosides were elucidated by extensive spectroscopic analysis including HR‐ESI‐MS and NMR data. The isolated nervisides D–H were evaluated for the cytotoxic activity in vitro against human‐tumor cell lines (CNE, Hep‐2 and HepG2) with the MTT method.
Zn2+ Complexes of 3,5‐Bis[(1,5,9‐triazacyclododecan‐3‐yloxy)methyl]phenyl Conjugates of Oligonucleotides as Artificial RNases: The Effect of Oligonucleotide Conjugation on Uridine Selectivity of the Cleaving Agent
Authors: Niittymäki Teija , Burakova Ekaterina , Laitinen Evelina , Leisvuori Anna , Virta Pasi , Lönnberg Harri 
Published: January 2013

Abstract2‐(3,5‐Bis{[1,5,9‐tris(trifluoroacetyl)‐1,5,9‐triazacyclododecan‐3‐yloxy]methyl}phenoxy)ethanol was synthesized and converted to a O‐(2‐cyanoethyl)‐N,N‐diisopropylphosphoramidite building block, 12. 2′‐O‐Methyl oligoribonucleotides incorporating a 2‐[(2S,4S,5R)‐4‐hydroxy‐5‐(hydroxymethyl)tetrahydrofuran‐2‐yl)ethyl 4‐oxopentanoate or a 2‐{2‐[2‐({[(2R,4S,5R)‐4‐hydroxy‐5‐(hydroxymethyl)tetrahydrofuran‐2‐yl]acetyl}amino)ethoxy]ethoxy}ethyl 4‐oxopentanoate non‐nucleosidic unit close to the 3′‐terminus were assembled on a solid support, the 4‐oxopentanoyl protecting groups were removed by treatment with hydrazinium acetate on‐support, and 12 was coupled to the exposed OH function. The deprotected conjugates were purified by HPLC, and their ability to cleave a complementary RNA containing either uridine or some other nucleoside at the potential cleaving site was compared. Somewhat unexpectedly, conjugation to an oligonucleotide did not enhance the catalytic activity of the Zn2+bis(azacrown) complex and virtually abolished its selectivity towards the uridine sites.
Rhopeptin A: First Cyclopeptide Isolated from Rhodobryum giganteum
Authors: Jiao Wei , Wu Zhijun , Chen Xiaozhen , Lu Runhua , Shao Huawu 
Published: January 2013

AbstractRhopeptin A was isolated as the first cyclopentapeptide from the moss Rhodobyum giganteum [Schwaegr.] Par. This novel compound consists of proline, phenylalanine, and 3‐hydroxyproline ring‐bonded amino acid residues connected to a tyrosine fragment via an ether bridge. Attached to a 3‐hydroxyproline unit is a side chain of pyroglutamic acid residue. The structure of the peptide was deduced from the 1D‐ and 2D‐NMR and MS data.
Synthesis of 2,N,N‐Trisubstituted 1H‐Indole‐1‐carbothioamides from 2‐(Acylmethyl)phenyl Isocyanides
Authors: Kobayashi Kazuhiro , Yamane Kazuya , Fukamachi Shuhei 
Published: January 2013

AbstractA convenient procedure for the synthesis of 2,N,N‐trisubstituted 1H‐indole‐1‐carbothioamides from 2‐(acylmethyl)phenyl isocyanides has been developed. Thus, these isocyanides are converted into (Z)‐ [1‐alkyl (or phenyl)‐2‐(2‐isothiocyanatophenyl)ethenyl] 1,1‐dimethylethyl carbonates via an easy two‐step sequence. Treatment with secondary amines gave thiourea intermediates which afforded with CF3COOH (TFA) the desired products in fair‐to‐good yields.