bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative metabolism of tussilagone in rat and human liver microsomes using ultra‐high‐performance liquid chromatography coupled with high‐resolution LTQ‐Orbitrap mass spectrometry
Authors: Zhang Xin‐Shi , Ren Wei , Bian Bao‐Lin , Zhao Hai‐Yu , Wang Shu
Published: August 2015

Rationale

Tussilagone is a major component in Tussilago farfara that has been widely used as an anti‐tussive herbal medicine for the treatment of bronchitis, cough and asthmatic disorders in the clinic. However, its metabolism has been poorly investigated. In order to clarify its in vitro metabolism, a comparative analysis of its metabolic profile in rat liver microsomes (RLMs) and human liver microsomes (HLMs) was carried out. Further, the cytochrome P450 isoforms (CYPs) involved in the metabolism were investigated.

Methods

In this work, the biotransformation of tussilagone in RLMs and HLMs was compared using ultra‐high‐performance liquid chromatography coupled with high‐resolution LTQ‐Orbitrap mass spectrometry (UHPLC/HRMS) and the CYPs involved in the metabolism were further investigated by recombinant human CYP enzymes.

Results

Totally, nine metabolites of tussilagone were identified in RLMs and HLMs based on the proposed MS/MS fragmentation pathways of tussilagone and the accurate MS/MS spectra. Among them, one metabolite (M9) was detected in both RLMs and HLMs while the other eight metabolites were only detected in HLMs. Three hydroxylation metabolites (M6, M7 and M8) were detected in the assay with individual recombinant P450s incubation. M6 was detected in all CYPs except CYP2A6 while M7 and M8 were only observed in CYP3A4.

Conclusions

The HR‐ESI‐MS/MS fragmentation behavior of tussilagone and its metabolic profile in RLMs and HLMs were investigated for the first time. The results demonstrated that the biotransformation of tussilagone involved hydrolysis of ester bonds at C‐14 and hydroxylation in the side chains at C‐12, C‐5' or C‐6'. Among the CYPs, CYP3A4 played an important role in the hydroxylation reaction of tussilagone in vitro. Furthermore, the results indicated a species‐related difference in the metabolism of tussilagone between RLMs and HLMs. This work provided basic information for the metabolism of tussilagone in RLMs and HLMs, which would help to better understand the pharmacological activities of tussilagone. Copyright © 2015 John Wiley & Sons, Ltd.
Breaking down Captcha using edge corners and fuzzy logic segmentation/recognition technique
Authors: Nachar Rabih Al. , Inaty Elie , Bonnin Patrick J. , Alayli Yasser
Published: August 2015

CAPTCHA is a security technique to allow a computer application to distinguish between computer and human access. Most of now a day CAPTCHA words have their characters connected together which makes them very difficult to be segmented and recognized. In this paper we present an efficient technique that first benefits from the intersections between characters in a word and then segment it based on the recognition of each segmented character. Edge corners (ECs) are used in both segmentation and recognition phases. A novel fuzzy logic‐based scheme is proposed to match characters using their ECs. Experimental results show the efficiency of the proposed scheme in terms of success rate using a large set of CAPTCHA's words. Copyright © 2015 John Wiley & Sons, Ltd.
A systematic review of the association between family meals and adolescent risk outcomes
Authors: Goldfarb Samantha S. , Tarver Will L. , Locher Julie L. , Preskitt Julie , Sen Bisakha
Published: August 2015

Objective

To conduct a systematic review of the literature examining the relationship between family meals and adolescent health risk outcomes.

Methods

We performed a systematic search of original empirical studies published between January 1990 and September 2013. Based on data from selected studies, we conducted logistic regression models to examine the correlates of reporting a protective association between frequent family meals and adolescent outcomes.

Results

Of the 254 analyses from 26 selected studies, most reported a significant association between family meals and the adolescent risk outcome‐of‐interest. However, model analyses which controlled for family connectedness variables, or used advanced empirical methods to account for family‐level confounders, were less likely than unadjusted models to report significant relationships.

Conclusions

The type of analysis conducted was significantly associated with the likelihood of finding a protective relationship between family meals and the adolescent outcome‐of‐interest, yet very few studies are using such methods in the literature.
A Discussion of Some Aspects of the Regimes for the Regulation of Insider Dealing in South Africa and the United States of America
Authors: Kawadza Herbert
Published: August 2015

Global regulators acknowledge the negative economic impact linked to insider dealing and have devised diverse regulatory frameworks aimed at minimizing its prevalence. Although their strategies differ, policy-makers realise that, with the inevitable internationalization of securities markets, the probability of cross-border insider trading escalates. With a view to providing a platform for regulatory re-examination and reform, this article discusses the divergent approaches that the United States and South Africa have adopted to counter the challenge of pervasive insider dealing. A paradox manifested with the US experience is that, while its theoretical prohibition of insider dealing is widely criticized as inadequate and inconsistent, robust enforcement has nonetheless led to strong institutions and a superior financial markets regime. The article concludes that the attainment of safer financial markets does not depend on the mere existence of superior proscriptions. Rather, it is the effective supervision of the sector and robust enforcement of those laws that enhance deterrence and ensure compliance.
Exposure of bivalve shellfish to titania nanoparticles under an environmental-spill scenario: Encounter, ingestion and egestion
Authors: Doyle John J. , Ward J. Evan , Mason Robert
Published: August 2015

Nanoparticles have applications in a diverse range of products including medications, detergents, cosmetics, paint, sunscreen and electronics, with an economic worth projected to reach $2.5 trillion dollars in 2015. Research into the effects of manufactured nanomaterials on the environment, however, has failed to keep pace with the high volume of commercial production. Whereas a number of studies have examined the effects of nanoparticles on aquatic species, little work has focused on the way in which benthic marine species encounter, ingest and depurate these materials. The purpose of this study was to examine the ingestion and depuration of titania nanoparticles (anatase) by the blue mussel (Mytilus edulis) and the eastern oyster (Crassostrea virginica) during a spill scenario (an acute exposure to elevated concentrations). Bivalves were exposed to nanoparticles either incorporated into marine snow, an environmentally relevant medium for pollutants, or added directly to seawater at a concentration of 4.5 mg L−1 for 2 h. After feeding, the animals were transferred to filtered seawater and allowed to depurate. Faeces and tissues were collected at 0, 6, 24, 72 and 120 h, post-exposure, and analysed for concentrations of titanium by inductively coupled plasma-mass spectrometry. Results indicated that the capture and ingestion of titania nanoparticles by both species was not dependent on the method of delivery (incorporated into marine snow or freely suspended). Additionally, greater than 90% of the titania nanoparticles, on average, were eliminated from the tissues after 6 h, and only trace amounts remained after 72 h. These data demonstrate that mussels and oysters readily ingest titania nanoparticles, but rapidly depurate the material within hours of an acute exposure suggesting that little would be transferred to secondary consumers including humans. Further research is required to determine if other species of suspension-feeders handle titania nanoparticles in a manner similar to bivalves.
Abundance of the spongeHymeniacidoncf.perlevisin a stressful environment of Patagonia: relationships withUlva lactucaand physical variables
Authors: Gastaldi Marianela , Firstater Fausto Nahuel , Daleo Pedro , Narvarte Maite Andrea
Published: August 2015

Understanding the variables (biotic or abiotic) controlling coastal communities is the main goal of ecology research and it is crucial to predict how communities will evolve under the increasing pressure on coastal systems by human activities. The general aims of this study were to assess the variables affecting the distribution of the fast-growing spongeHymeniacidoncf.perlevis, and to evaluate if physical stressful conditions have an influence in the relationship betweenHymeniacidonand the sea lettuceUlva lactuca. Specifically, the aims were to evaluate the abundance patterns ofHymeniacidonandUlvaand to assess the relationship ofUlvaand physical variables on the abundance ofHymeniacidonat both intertidal and subtidal.HymeniacidonandUlvashowed opposite abundance patterns.Hymeniacidonwas more abundant in sites withoutUlva, and negatively correlated withUlvaabundance at both heights. IntertidalHymeniacidonabundance was not correlated with physical variables, but subtidalHymeniacidonwas.
Effects of wave exposure on the abundance and composition of amphipod and tanaidacean assemblages inhabiting intertidal coralline algae
Authors: Bueno M. , Dena-Silva S.A. , Flores A.A.V. , Leite F.P.P.
Published: August 2015

Peracarid crustaceans are an important component of the vagile fauna associated with coralline algal beds, which often characterize the infralittoral fringe of tropical rocky shores. Among other variables affecting faunal assemblages, sedimentation, food supply and oxygen concentration within mats or turfs of coralline algae may greatly depend on the exposure to waves. In this study, peracarid assemblages were compared at replicated rocky shores within different levels of wave exposure, along a coastline in south-eastern Brazil. Overall amphipod diversity (11 species) was much higher than tanaidacean diversity (two species). Correlation analyses did not support any biological interactions between amphipods and tanaidaceans. Habitat complexity, while apparently limiting amphipod populations, did not affect tanaidaceans at a local scale. Amphipod abundance, not assemblage structure, was positively affected by wave exposure, probably improving oxygen concentration levels and renewal of food resources. Rather than abundance, which remains fairly stable, exposure to waves determined species identity in tanaidaceans, withZeuxo coralensisfound at exposed shores andLeptocheliaaff.dubiafound at sheltered shores, except for twoL.aff.dubiaindividuals found at one of the exposed sites. Differences in the supply of sediment and the ability of these species in manipulating grains for tube building may explain such a striking pattern.
Interlaboratory study on the quantification of calcium phosphate phases by Rietveld refinement
Authors: Döbelin Nicola
Published: August 2015

An interlaboratory study (ILS, round robin) was conducted to assess the accuracy and precision of the phase quantification of calcium phosphate (CaP) bioceramics by X-ray diffraction (XRD) and Rietveld refinement. For that purpose, a mixture of hydroxyapatite and β-tricalcium phosphate, two CaP phases commonly used in synthetic bone graft substitutes, was prepared and sent to 12 laboratories for XRD analysis. Results from 26 different instruments were received and evaluated statistically according to ASTM E691 – 13. The statistical analysis revealed that the reproducibility standard deviation of phase quantities was approximately two times greater than the repeatability standard deviation, which is obtained by repeating the analysis on a single instrument configuration multiple times. The 95% reproducibility limit for phase quantities was R = ±1.67 wt%. The study also demonstrated that several participants overinterpreted their data in an attempt to refine crystallite sizes of the minor phase.
Three Decades of Disasters: A Review of Disaster-Specific Literature from 1977–2009
Authors: Smith Erin , Wasiak Jason , Sen Ayan , Archer Frank , Burkle Frederick M.
Published: August 2015

Introduction:

The potential for disasters exists in all communities. To mitigate the potential catastrophes that confront humanity in the new millennium, an evidence-based approach to disaster management is required urgently. This study moves toward such an evidence-based approach by identifying peer-reviewed publications following a range of disasters and events over the past three decades.

Methods:

Peer-reviewed, event-specific literature was identified using a comprehensive search of the electronically indexed database, MEDLINE (1956–January 2009). An extended comprehensive search was conducted for one event to compare the event-specific literature indexed in MEDLINE to other electronic databases (EMBASE, CINAHL, AMED, CENTRAL, Psych Info, Maternity and Infant Care, EBM Reviews).

Results:

Following 25 individual disasters or overwhelming crises, a total of 2,098 peer-reviewed, event-specific publications were published in 789 journals (652 publications following disasters/events caused by natural hazards, 966 following human-made/technological disasters/events, and 480 following conflict/complex humanitarian events).The event with the greatest number of peer-reviewed, event-specific publications was the 11 September 2001 terrorist attacks (686 publications). Prehospital and Disaster Medicine published the greatest number of peer-reviewed, event-specific publications (54), followed by Journal of Traumatic Stress (42), Military Medicine (40), and Psychiatric Services (40). The primary topics of event-specific publications were mental health, medical health, and response. When an extended, comprehensive search was conducted for one event, 75% of all peer-reviewed, event-specific publications were indexed in MEDLINE.

Conclusions:

A broad range of multi-disciplinary journals publish peer-reviewed, event-specific publications. While the majority of peer-reviewed, event-specific literature is indexed in MEDLINE, comprehensive search strategies should include EMBASE to increase yield.
TWO UNPUBLISHED LETTERS BY DAVID RICARDO ON A MONETARY PAMPHLET BY SAMUEL TERTIUS GALTON
Authors: Depoortère Christophe
Published: August 2015

This article transcripts and analyzes two hitherto unpublished letters by David Ricardo. The first one (6 December 1812), was addressed to Leonard Horner. In the second one (3 March 1813), Ricardo thanked Samuel Tertius Galton for having sent him the pamphlet on monetary questions Galton had just published. This second letter was very useful to identify the work discussed by Ricardo in the first letter. Indeed, in his writing to Horner, Ricardo commented extensively on Galton’s manuscript. He dealt with important monetary issues such as the distinction between a deteriorated and a depreciated currency, the determination of the par of exchange between countries admitting two different monetary standards, and the distinction between an increased issue of notes by the Bank of England and an increased quantity of money in circulation.
Resolving bundled microtubules using anti-tubulin nanobodies
Authors: Mikhaylova Marina , Cloin Bas M. C. , Finan Kieran , van den Berg Robert , Teeuw Jalmar , Kijanka Marta M. , Sokolowski Mikolaj , Katrukha Eugene A. , Maidorn Manuel , Opazo Felipe , Moutel Sandrine , Vantard Marylin , Perez Frank , van Bergen en Henegouwen Paul M. P. , Hoogenraad Casper C. , Ewers Helge , Kapitein Lukas C
Published: August 2015

Microtubules are hollow biopolymers of 25-nm diameter and are key constituents of the cytoskeleton. In neurons, microtubules are organized differently between axons and dendrites, but their precise organization in different compartments is not completely understood. Super-resolution microscopy techniques can detect specific structures at an increased resolution, but the narrow spacing between neuronal microtubules poses challenges because most existing labelling strategies increase the effective microtubule diameter by 20–40 nm and will thereby blend neighbouring microtubules into one structure. Here we develop single-chain antibody fragments (nanobodies) against tubulin to achieve super-resolution imaging of microtubules with a decreased apparent diameter. To test the resolving power of these novel probes, we generate microtubule bundles with a known spacing of 50–70 nm and successfully resolve individual microtubules. Individual bundled microtubules can also be resolved in different mammalian cells, including hippocampal neurons, allowing novel insights into fundamental mechanisms of microtubule organization in cell- and neurobiology.
Adaptive quantum computation in changing environments using projective simulation
Authors: Tiersch M. , Ganahl E. J. , Briegel H. J.
Published: August 2015

Quantum information processing devices need to be robust and stable against external noise and internal imperfections to ensure correct operation. In a setting of measurement-based quantum computation, we explore how an intelligent agent endowed with a projective simulator can act as controller to adapt measurement directions to an external stray field of unknown magnitude in a fixed direction. We assess the agent’s learning behavior in static and time-varying fields and explore composition strategies in the projective simulator to improve the agent’s performance. We demonstrate the applicability by correcting for stray fields in a measurement-based algorithm for Grover’s search. Thereby, we lay out a path for adaptive controllers based on intelligent agents for quantum information tasks.
A “footprint” of plant carbon fixation cycle functions during the development of a heterotrophic fungus
Authors: Lyu Xueliang , Shen Cuicui , Xie Jiatao , Fu Yanping , Jiang Daohong , Hu Zijin , Tang Lihua , Tang Liguang , Ding Feng , Li Kunfei , Wu Song , Hu Yanping , Luo Lilian , Li Yuanhao , Wang Qihua , Li Guoqing , Cheng Jiasen
Published: August 2015

Carbon fixation pathway of plants (CFPP) in photosynthesis converts solar energy to biomass, bio-products and biofuel. Intriguingly, a large number of heterotrophic fungi also possess enzymes functionally associated with CFPP, raising the questions about their roles in fungal development and in evolution. Here, we report on the presence of 17 CFPP associated enzymes (ten in Calvin-Benson-Basham reductive pentose phosphate pathway and seven in C4-dicarboxylic acid cycle) in the genome of Sclerotinia sclerotiorum, a heterotrophic phytopathogenic fungus and only two unique enzymes: ribulose-1, 5-bisphosphate carboxylase-oxygenase (Rubisco) and phosphoribulokinase (PRK) were absent. This data suggested an incomplete CFPP-like pathway (CLP) in fungi. Functional profile analysis demonstrated that the activity of the incomplete CLP was dramatically regulated during different developmental stages of S. sclerotiorum. Subsequent experiments confirmed that many of them were essential to the virulence and/or sclerotial formation. Most of the CLP associated genes are conserved in fungi. Phylogenetic analysis showed that many of them have undergone gene duplication, gene acquisition or loss and functional diversification in evolutionary history. These findings showed an evolutionary links in the carbon fixation processes of autotrophs and heterotrophs and implicated the functions of related genes were in course of continuous change in different organisms in evolution.
The antioxidant compound tert-butylhydroquinone activates Akt in myocardium, suppresses apoptosis and ameliorates pressure overload-induced cardiac dysfunction
Authors: Zhang Yongtao , Fang Liu Fang , Bi Xiaolei , Wang Shuangxi , Wu Xiao , Jiang Fan
Published: August 2015

Tert-butylhydroquinone (TBHQ) is an antioxidant compound which shows multiple cytoprotective actions. We evaluated the effects of TBHQ on pathological cardiac remodeling and dysfunction induced by chronic overload. Pressure overload was created by transverse aortic constriction (TAC) in male C57BL/6 mice. TBHQ was incorporated in the diet and administered for 4 weeks. TBHQ treatment prevented left ventricular dilatation and cardiac dysfunction induced by TAC and decreased the prevalence of myocardial apoptosis. The beneficial effects of TBHQ were associated with an increase in Akt activation, but not related to activations of Nrf2 or AMP-activated protein kinase. TBHQ-induced Akt activation was accompanied by increased phosphorylation of Bad, glycogen synthase kinase-3β (GSK-3β) and mammalian target of rapamycin (mTOR). Mechanistically, we showed that in cultured H9c2 cells and primary cardiac myocytes, TBHQ stimulated Akt phosphorylation and suppressed oxidant-induced apoptosis; this effect was abolished by wortmannin or an Akt inhibitor. Blockade of the Akt pathway in vivo accelerated cardiac dysfunction and abrogated the protective effects of TBHQ. TBHQ also reduced the reactive aldehyde production and protein carbonylation in stressed myocardium. We suggest that TBHQ treatment may represent a novel strategy for timely activation of the cytoprotective Akt pathway in stressed myocardium.
The Effects of Combined Treatment with Naringin and Treadmill Exercise on Osteoporosis in Ovariectomized Rats
Authors: SUN Xiaolei , Fengbo LI , Xinlong MA , Jianxiong MA , ZHAO Bin , ZHANG Yang , Yanjun LI , Jianwei LV , MENG Xinmin
Published: August 2015

Osteoporosis is a disease characterized by low bone mass and progressive destruction of bone microstructure, resulting in increased the risk of fracture. Previous studies have demonstrated the effect of naringin (NG) or treadmill exercise (EX) on osteoporosis, however, reports about effects of NG plus EX on osteoporosis are limited. This study was designed to investigate the impact of combined treatment with naringin and treadmill exercise on osteoporosis in ovariectomized (OVX) rats. Three months after bilateral ovariectomy, Seventy-five rats were randomly assigned to the following treatment groups: OVX, sham-operated (SHAM), NG, EX, or NG plus EX treatment. Treatments were administered for 60 days. Bone metabolism, bone mineral density, trabecular bone parameters, immunohistochemistry and the bone strength were evaluated. Compared to the OVX groups, all treatments increased bone volume (BV/TV), trabecula number (Tb.N), trabecula thickness (Tb.Th), bone mineral density (BMD) and mechanical strength. NG + EX showed the strongest effects on BV/TV, Tb.Th and biomechanical strength. Additionally, decreased C-terminal telopeptides of type I collagen (CTX-1) and enhanced osteocalcin (OCN) expression were observed in the NG + EX group. The present study demonstrates that the NG + EX may have a therapeutic advantage over each monotherapy for the treatment of osteoporosis.
A time-course study of long term over-expression of ARR19 in mice
Authors: Qamar Imteyaz , Ahmad Mohammad Faiz , Narayanasamy Arul
Published: August 2015

A leucine-rich protein, ARR19 (androgen receptor corepressor-19 kDa), is highly expressed in male reproductive organs and moderately in others. Previously, we have reported that ARR19 is differentially expressed in adult Leydig cells during the testis development and inhibits steroidogenesis by reducing the expression of steroidogenic enzymes. Whereas in prostate, ARR19 represses the transcriptional activity of AR (androgen receptor), it is important for male sexual differentiation and maturation in prostate and epididymis, through the recruitment of HDAC4. In this study we show that long term adenovirus mediated overexpression of ARR19 in mice testis has the potential of inhibiting the differentiation of testicular and prostatic cells by reducing the size of testis and prostate but has no effect on the growth of seminal vesicles. Further, it reduces the level of progesterone and testosterone by reducing the steroidogenic enzymes such as 3HSD, P450c17 and StAR. This is the first study reporting a time-course analysis of the implications of long term overexpression of ARR19 in mice testis and its effect on other organs such as prostate and seminal vesicles. Taken together, these results suggest that ARR19 may play an important role in the differentiation of male reproductive organs such as testis and prostate.
Ion pair-based dispersive liquid–liquid microextraction combined with UV-Vis spectrophotometry as a circuitous assay for nitrite
Authors: Poormoghadam Parisa , Larki Arash , Rastegarzadeh Saadat
Published: August 2015

This paper proposes a fast and reliable dispersive liquid–liquid microextraction (DLLME) method for the determination of trace levels of nitrite by UV-Vis spectrophotometry.
Stable and compact zwitterionic polydiacetylene micelles with tumor-targeting properties
Authors: Theodorou Ioanna , Anilkumar Parambath , Lelandais Benoit , Clarisse Damien , Doerflinger Anaëlle , Gravel Edmond , Ducongé Frédéric , Doris Eric
Published: August 2015

Stealth zwitterionic polydiacetylene-micelles are evaluated in vivo for the passive targeting of tumors.
The discovery of novel antifungal scaffolds by structural simplification of the natural product sampangine
Authors: Jiang Zhigan , Liu Na , Hu Dandan , Dong Guoqiang , Miao Zhenyuan , Yao Jianzhong , He Haiying , Jiang Yuanying , Zhang Wannian , Wang Yan , Sheng Chunquan
Published: August 2015

Structural simplification of the natural product sampangine led to the discovery of two novel antifungal compounds with excellent activity and low toxicity.
Coordination structure and charge transfer in microsolvated transition metal hydroxide clusters [MOH]+(H2O)1–4
Authors: Marsh Brett M. , Voss Jonathan M. , Zhou Jia , Garand Etienne
Published: August 2015

Infrared vibrational predissociation spectra of transition metal hydroxide clusters, [MOH]+(H2O)1–4·D2 with M = Mn, Fe, Co, Ni, Cu, and Zn, are presented and analyzed, showing solvent driven changes in coordination and charge transfer.
Synthesis of BiOI@(BiO)2CO3 facet coupling heterostructures toward efficient visible-light photocatalytic properties
Authors: Ding Chenghua , Cao Fengpu , Ye Liqun , Liu Kecheng , Xie Haiquan , Jin Xiaoli , Su Yurong
Published: August 2015

BiOI@(BiO)2CO3 facet coupling heterostructures were synthesized, and showed much higher photocatalytic activity than BiOI and (BiO)2CO3 under visible light.
Synthesis of a Bi2S3/CeO2 nanocatalyst and its visible light-driven conversion of CO2 into CH3OH and CH4
Authors: Ijaz Sana , Ehsan Muhammad Fahad , Ashiq Muhammad Naeem , He Tao
Published: August 2015

The Bi2S3/CeO2 nanocatalyst can efficiently photoreduce CO2 into CH3OH and CH4 under visible-light irradiation due to Bi2S3 sensitization and semiconductor combination.
Bridging the opposite chemistries of tantalum and tungsten polyoxometalates
Authors: Molina P. I. , Sures D. J. , Miró P. , Zakharov L. N. , Nyman M.
Published: August 2015

Reaction of Ta peroxometalate and tungstate affords the first systematic series of Ta/W isopolyoxometalates. An analogous reaction system yields a Nb/W cluster. The electronic structure and stability of these clusters varies as a function of the group V metal content, as inferred from spectroscopic, electrochemical and mass-spectrometry analysis and confirmed by DFT calculations.
Lanthanide(iii) and lead(ii) complexes of a chiral nonaaza macrocyclic amine based on 1,2-diaminocyclopentane
Authors: Gregoliński Janusz , Ślepokura Katarzyna , Lisowski Jerzy
Published: August 2015

We report the synthesis, spectroscopic characterization and X-ray crystal structures of a series of helical complexes of a new chiral macrocycle based on diaminocyclopentane fragments. In the case of a Pb(ii) derivative the NMR data indicate a dynamic process corresponding to partial wrapping and unwrapping of the macrocycle resulting in the switching of the helix axis.
Design and discovery of 3-aryl-5-substituted-isoquinolin-1-ones as potent tankyrase inhibitors
Authors: Elliott Richard J. R. , Jarvis Ashley , Rajasekaran Mohan B. , Menon Malini , Bowers Leandra , Boffey Ray , Bayford Melanie , Firth-Clark Stuart , Key Rebekah , Aqil Rehan , Kirton Stewart B. , Niculescu-Duvaz Dan , Fish Laura , Lopes Filipa , McLeary Robert , Trindade Ines , Vendrell Elisenda , Munkonge Felix , Porter Rod , Perrior Trevor , Springer Caroline , Oliver Antony W. , Pearl Laurence H. , Ashworth Alan , Lord Christopher J.
Published: August 2015

The tankyrase proteins (TNKS, TNKS2) are attractive anti-cancer drug targets, particularly as inhibition of their catalytic activity has been shown to antagonise oncogenic WNT signalling.
Biogenic synthesis of a Ag–graphene nanocomposite with efficient photocatalytic degradation, electrical conductivity and photoelectrochemical performance
Authors: Khan Mohammad Ehtisham , Khan Mohammad Mansoob , Cho Moo Hwan
Published: August 2015

Visible light-driven photocatalytic degradation of organic pollutants using the Ag–graphene nanocomposite.
Nanoparticle cluster gas sensor: Pt activated SnO2 nanoparticles for NH3 detection with ultrahigh sensitivity
Authors: Liu Xu , Chen Nan , Han Bingqian , Xiao Xuechun , Chen Gang , Djerdj Igor , Wang Yude
Published: August 2015

Pt activated SnO2 nanoparticle clusters were synthesized by a simple solvothermal method for use in highly sensitive ammonia gas sensors.
Imidazoles from nitroallylic acetates and α-bromonitroalkenes with amidines: synthesis and trypanocidal activity studies
Authors: Gopi Elumalai , Kumar Tarun , Menna-Barreto Rubem F. S. , Valença Wagner O. , da Silva Júnior Eufrânio N. , Namboothiri Irishi N. N.
Published: August 2015

One-pot cascade reactions of amidines with nitroallylic acetates and α-bromonitroalkenes provide functionalized imidazoles that exhibit trypanocidal activity.
Organic acids as efficient catalysts for group transfer polymerization of N,N-disubstituted acrylamide with silyl ketene acetal: polymerization mechanism and synthesis of diblock copolymers
Authors: Kikuchi Seiya , Chen Yougen , Kitano Kodai , Takada Kenji , Satoh Toshifumi , Kakuchi Toyoji
Published: August 2015

The GTP of N,N-disubstituted acrylamide using organic acid and silyl ketene acetal was intensively investigated.
Integrated traditional Chinese and western medicine modulator for overcoming the multidrug resistance with carbon nanotubes
Authors: Zhang Haijun , Xiong Jian , Guo Liting , Patel Nishant , Guang Xueneng
Published: August 2015

GA/Dox/P-gp Ab-CNTs, integrated specific targeting, P-gp inhibitor and chemotherapeutic agent, could represent a promising modulator for overcoming tumor MDR.
One-pot synthesis and assembly of melamine-based nanoparticles for microporous polymer organic frameworks and their application as a support for a silver nanoparticle catalyst
Authors: Zhao Xiaolong , Yan Na
Published: August 2015

A facile one-pot route was developed to obtain organic nanoparticles for fabrication of microporous POFs which can be utilized to entrap Ag nanoparticles and show excellent catalytic performance for organic dyes such as methylene blue in water.
Phenylphosphinacalix[3]trifuran: synthesis, coordination and application in the Suzuki–Miyaura cross-coupling reaction in water
Authors: Sun Yue , Yan Meng-Qi , Liu Yan , Lian Ze-Yu , Meng Tong , Liu Sheng-Hua , Chen Jian , Yu Guang-Ao
Published: August 2015

Phenylphosphinacalix[3]trifuran and supramolecular assemblies with palladium have been synthesized. Phenylphosphinacalix[3]trifuran affords turnover numbers as high as 3.05 × 107 in Suzuki–Miyaura cross-coupling reactions in pure water.
A novel shuttle-like Fe3O4–Co3O4self-assembling architecture with highly reversible lithium storage
Authors: Shang Kaina , Li Wentao , Liu Yongmei , Zhang Wenguang , Yang Hui , Xie Jiqing , Liu Zuyan , Chou Shu-Lei , Zhao Lingzhi , Zeng Ronghua
Published: August 2015

An unprecedented shuttle-like Fe3O4–Co3O4self-assembling architecture is obtained through a facile hydrothermal method. Obviously, the electrochemical performance of the obtained composite is large enhanced in comparison with that of pristine Co3O4.
Ultrafast dynamics of a molecular rotor in chemical and biological nano-cavities
Authors: Gavvala Krishna , Satpathi Sagar , Hazra Partha
Published: August 2015

Excited state dynamics of CCVJ are investigated inside the nano-cavities of CD and HSA using steady-state and femtosecond up-conversion techniques.
CO2-tolerant oxygen-permeable perovskite-type membranes with high permeability
Authors: Zhu Jiawei , Guo Shaobin , Chu Zhenyu , Jin Wanqin
Published: August 2015

By reasonably selecting B-site cations, SrFe0.9Ta0.1O3−δand SrFe0.8Sb0.2O3−δmembranes have been developed to combine excellent CO2tolerance and oxygen permeability.
Synthesis of porous peanut-like LiNi0.5Mn1.5O4 cathode materials through an ethylene glycol-assisted hydrothermal method using urea as a precipitant
Authors: Wang Li , Liu Guijuan , Wu Wei , Chen Dan , Liang Guangchuan
Published: August 2015

The porous peanut-like LiNi0.5Mn1.5O4 cathode material synthesized by an EG-assisted hydrothermal method exhibits better electrochemical properties. A possible formation mechanism for the Ni0.25Mn0.75CO3 precursor was proposed.
Enhanced efficiency of polymer photovoltaic cells via the incorporation of a water-soluble naphthalene diimide derivative as a cathode interlayer
Authors: Zhao Kang , Ye Long , Zhao Wenchao , Zhang Shaoqing , Yao Huifeng , Xu Bowei , Sun Mingliang , Hou Jianhui
Published: August 2015

A novel water-soluble naphthalene diimide derivative was utilized as a cathode interlayer for two types of high performance polymer photovoltaic cells.
Mammalian clock output mechanisms
Authors: Kalsbeek Andries , Yi Chun-Xia , Cailotto Cathy , la Fleur Susanne E. , Fliers Eric , Buijs Ruud M
Published: August 2015

In mammals many behaviours (e.g. sleep–wake, feeding) as well as physiological (e.g. body temperature, blood pressure) and endocrine (e.g. plasma corticosterone concentration) events display a 24 h rhythmicity. These 24 h rhythms are induced by a timing system that is composed of central and peripheral clocks. The highly co-ordinated output of the hypothalamic biological clock not only controls the daily rhythm in sleep–wake (or feeding–fasting) behaviour, but also exerts a direct control over many aspects of hormone release and energy metabolism. First, we present the anatomical connections used by the mammalian biological clock to enforce its endogenous rhythmicity on the rest of the body, especially the neuro-endocrine and energy homoeostatic systems. Subsequently, we review a number of physiological experiments investigating the functional significance of this neuro-anatomical substrate. Together, this overview of experimental data reveals a highly specialized organization of connections between the hypothalamic pacemaker and neuro-endocrine system as well as the pre-sympathetic and pre-parasympathetic branches of the autonomic nervous system.
Ubiquitin: preparative chemical synthesis, purification and characterization
Authors: OGUNJOBI O. , RAMAGE R.
Published: August 2015

Summary

An improved total synthesis of ubiquitin has been achieved by the Fmoc/t-butyl solid-phase methodology using NGPmc protection of the Arg residues [1]. Optimization of the purification protocol has offered the material in substantial quantity (90 mg) in an overall yield of 4.2%. Characterization of the isolated products has opened the way to the studies of the folding pathway and the preparation of structural analogues.
Protein engineering to change thermal stability for food enzymes
Authors: Goodenough Peter W. , Jenkins John A.
Published: August 2015

Summary

In this review we have briefly indicated how the present state of knowledge allows proteins to be mutated to increase or decrease stability. We have discussed experiments on both model proteins and those of relevance to the food industry, and show how hydrophobic forces are a major driving force for folding as well as having a major role in thermostability. We have also indicated the large contribution that hydrogen bonding, electrostatic interactions and, in a less well predicted way, disulphide bridges make to thermostability.
A comparison of peroxidase and cytochrome P-450
Authors: Wood Paul M.
Published: August 2015

Summary

A peroxidase has 1-electron oxidation as its characteristic activity, while that of cytochrome P-450 is hydroxylation. Both catalytic cycles involve similar high valency states of iron. However, a peroxidase can only accept electrons at the haem edge, while the substrate for cytochrome P-450 is bound in a precise orientation before the active state is created.
Phosphorescent porphyrin probes in biosensors and sensitive bioassays
Authors: Papkovsky D. B. , O'Riordan T. , Soini A.
Published: August 2015

Platinum(II) and palladium(II) complexes of porphyrins and related tetrapyrrolic pigments emit strong phosphorescence at room temperatures, which is characterized by long lifetimes falling into the sub-millisecond range and long-wave spectral characteristics. These features make the dyes useful as probes for a number of bioanalytical applications, particularly those employing time-resolved fluorescent detection. They can provide high sensitivity and selectivity, together with rather simple instrumental set-up. A number of analytical systems are now under development that are based on the use of phosphorescent porphyrin probes. Experimental results are presented on the following systems: (i) fibre-optic phosphorescence lifetime-based oxygen sensor on the basis of hydrophobic platinum-porphyrins and development of advanced sensing materials and prototype instrumentation; (ii) practical applications of the optical oxygen sensor, including a sensitive immunosensor that employs glucose oxidase labels, a rapid screening method for cell viability in microtitre-plate format, non-destructive measurement of oxygen in packaged foods and reagentless biosensors for metabolites (glucose, lactate); and (iii) the use of water-soluble platinum- and palladium-porphyrins as labels for ultra-sensitive time-resolved phosphorescence immunoassays.
Direct electron transfer catalysed by enzymes: application for biosensor development
Authors: Ghindilis A.
Published: August 2015

The ability to catalyse an electrode reaction via direct (mediatorless) electron transfer has been demonstrated for a number of redox enzymes. In the case of mediatorless electron transfer, the electron is transferred directly from the electrode to the substrate molecule via the active site of the enzyme, or vice versa. The electron itself is the second substrate for the reaction. An important point characterizing bioelectrocatalysis is the catalytic removal of the reaction over-voltage. Therefore the enzyme attached to the electrode is able to catalyse electrode reaction and forms a ‘molecular transducer’. The substrate can be detected by potentiometric measurement of the removal of reaction over-voltage. The enzyme laccase is able to catalyse the reaction of oxygen electroreduction. Therefore a laccase molecular layer attached to the electrode surface forms an oxygen transducer. The formation of the layer results in a change of the electrocatalytic feature of the electrode. Laccase label coupled with either ligand or receptor allows the detection of ligand-receptor complex formation/dissociation on the electrode surface. The detection is virtually reagentless. The substrates for the reaction are molecular oxygen and the electron itself. Numerous reagentless immunosensors of different formats (competitive, displacement and sandwich) have been developed, as well as the reagentless detection system for immunofiltration/immunochromatography.
Replicative senescence as a barrier to human cancer
Authors: Parkinson E. K. , Munro J. , Steeghs K. , Morrison V. , Ireland H. , Forsyth N. , Fitzsimmons S. , Bryce S.
Published: August 2015

There is evidence that one critically short telomere may be recognized as DNA damage and, as a consequence, induce a p53/p21WAF- and pl6INK4A-dependent G1 cell cycle checkpoint to cause senescence. Additionally, senescence via a p53-and pl6INK4A-dependent mechanism can be induced by the over- or under-stimulation of certain signalling pathways that are involved in cancer. Central to this alternative senescence mechanism is the pl4ARF protein, which connects oncogene activation, but not DNA damage, to p53 activation and senescence. We find that immortal keratinocytes almost invariably have dysfunctional p53 and p16 and have high levels of telomerase, but very often express a wild-type pl4ARF. Furthermore, when normal keratinocytes senesce they show a striking elevation of p16 protein, but not of p14ARF or its downstream targets p53 and p21WAF. These results suggest that p16, rather than pl4ARF, is the more important gene in human keratinocyte senescence, but do not exclude a co-operative role for pl4ARF, perhaps in the induction of senescence by activated oncogenes in neoplasia. Regardless of mechanism, these results suggest that replicative senescence acts as a barrier to human cancer development.
l-Glutamate as a Central Neurotransmitter: Looking Back
Authors: Watkins J. C.
Published: August 2015

The high concentration in brain of unbound l-glutamic acid (in its anionic form, l-glutamate) fuelled considerable speculation as to its role in central nervous function more than 50 years ago. Claims in the 1940s that it could improve cognitive acuity in patients with mental impairment were particularly intriguing, though later refuted. In the early 1950s Hayashi [(1954) Keio J. Med. 3, 183–192] found that l-glutamate could cause convulsions and proposed that it might be a central synaptic transmitter. Soon thereafter, Curtis and colleagues [Curtis, Phillis and Watkins (1959) Nature (London) 183, 611] showed that l-glutamate depolarized and excited central neurons, as expected for an excitatory transmitter; however, various aspects of the action of l-glutamate seemed to argue strongly against a transmitter function. This negative view prevailed for some 20 years, before compelling evidence for such a role was adduced. Over the last two decades, extensive research has revealed a host of glutamate receptor subtypes, subserving several different functions in excitatory synaptic transmission. This paper gives a very brief and personal overview of the development of the field over the last 50 years from a mainly pharmacological standpoint.
Integrin Structure
Authors: Humphries M.J.
Published: August 2015

The integrins are a family of α,β heterodimeric receptors that mediate dynamic linkages between extracellular adhesion molecules and the intracellular actin cytoskeleton. Integrins are expressed by all multicellular animals, but their diversity varies widely among species; for example, in mammals, 19 α and 8β subunit genes encode polypeptides that combine to form 25 different receptors, whereas the Drosophila and Caenorhabditis genomes encode only five and two integrin a subunits respectively. Thousands of studies over the last two decades have investigated the molecular, cellular and organismal basis of integrin function. Gene deletion has demonstrated essential roles for almost all integrins, with the defects suggesting widespread contributions to both the maintenance of tissue integrity and the promotion of cellular migration. Integrin-ligand interactions are now considered to provide physical support for cells in order to maintain cohesion, to permit the generation of traction forces to enable movement, and to organize signalling complexes to modulate differentiation and cell fate. Animal-model studies have also shown that integrins contribute to the progression of many common diseases, and have implicated them as potential therapeutic targets. The use of anti-integrin monoclonal antibodies and ligand-mimetic peptides has validated this suggestion for inflammatory, neoplastic, traumatic and infectious conditions. Thus, to understand more about the mechanisms underlying tissue organization and cellular trafficking, and to identify approaches for regulating these processes in disease, there is intense interest in determining the molecular basis of integrin function. It is important to state at the outset that the tertiary structure of the integrin dimer is unknown. Our current understanding of the molecular basis of integrin function is therefore compiled from the results of a large number of studies that have employed a wide range of complementary technologies.
Potential use of stem cells from bone marrow to repair the extracellular matrix and the central nervous system
Authors: Prockop D. J. , Azizi S. A. , Colter D. , DiGirolamo C. , Kopen G. , Phinney D. G.
Published: August 2015

A subset of stem-like cells from bone marrow that are referred to as marrow stromal cells (MSCs) have been shown to be capable of differentiating into osteoblasts, chondrocytes, adipocytes, myocytes, astrocytes and perhaps neurons. Recently, conditions have been developed where human MSCs can be expanded almost without limit in culture without apparently losing their multi-potentiality for differentiation. The cells appear to be potentially useful for the repair of extracellular matrix and the central nervous system.
Morphogenetic messages are in the extracellular matrix: biotechnology from bench to bedside
Authors: Reddi A. H.
Published: August 2015

The origin and evolution of multicellular metazoa was accompanied by the appearance of extracellular matrix. The demineralized extracellular matrix of bone is enriched in morphogenetic proteins that induce bone. Bone morphogenetic proteins (BMPs) are intimately bound to collagens. BMP-4 has high affinity for type-IV collagen, and other binding proteins such as noggin and chordin. Soluble morphogens are kept in the solid state by extracellular matrix. In this sense Nature used the principles of affinity matrices long before humans patented the principle of affinity chromatography.
Expression of recombinant human type I-III collagens in the yeast Pichia pastoris
Authors: Myllyharju J. , Nokelainen M. , Vuorela A. , Kivirikko K. I.
Published: August 2015

An efficient expression system for recombinant human collagens will have numerous scientific and medical applications. However, most recombinant systems are unsuitable for this purpose, as they do not have sufficient prolyl 4-hydroxylase activity. We have developed methods for producing the three major fibril-forming human collagens, types I, II and III, in the methyl-otrophic yeast Pichia pastoris. These methods are based on co-expression of procollagen polypeptide chains with the α- and β-subunits of prolyl 4-hydroxylase. The triple-helical type-I, -II and -III procollagens were found to accumulate predominantly within the endoplasmic reticulum of the yeast cells and could be purified from the cell lysates by a procedure that included a pepsin treatment to convert the procollagens into collagens and to digest most of the non-collagenous proteins. All the purified recombinant collagens were identical in 4-hydroxyproline content with the corresponding non-recombinant human proteins, and all the recombinant collagens formed native-type fibrils. The expression levels using single-copy integrants and a 2 litre bioreactor ranged from 0.2 to 0.6 g/l depending on the collagen type.
Structural aspects of agonism and antagonism in the oestrogen receptor
Authors: Pike A. C. W. , Brzozowski A. M. , Walton J. , Hubbard R. E. , Bonn T. , Gustafsson J-Å. , Carlquist M.
Published: August 2015

We have determined the three-dimensional structures of both α- and β-forms of the ligand-binding domain of the oestrogen receptor (ER) in complexes with a range of receptor agonists and antagonists. Here, we summarize how these structures provide both an understanding of the ER's distinctive pharmacophore and a rationale for its ability to bind a diverse range of chemically distinct compounds. In addition, these studies provide a unique insight into the mechanisms that underlie receptor activation, as well as providing a structural basis for the antagonist action of molecules, such as raloxifene.