bluuebunny/crossref_metadata_2025 huggingface dataset:
Searching Online Mendelian Inheritance in Man (OMIM) for Information on Genetic Loci Involved in Human Disease
Authors: Baxevanis Andreas D.
Published: March 2012

Online Mendelian Inheritance in Man (OMIM) is a comprehensive compendium of information on human genes and genetic disorders, with a particular emphasis on the interplay between observed phenotypes and underlying genotypes. This unit focuses on the basic methodology for formulating OMIM searches and illustrates the types of information that can be retrieved from OMIM, including descriptions of clinical manifestations resulting from genetic abnormalities. This unit also provides information on additional relevant medical and molecular biology databases. A basic knowledge of OMIM should be part of the armamentarium of physicians and scientists with an interest in research on the clinical aspects of genetic disorders. Curr. Protoc. Bioinform. 37:1.2.1‐1.2.10. © 2012 by John Wiley & Sons, Inc.
Using BLAT to Find Sequence Similarity in Closely Related Genomes
Authors: Bhagwat Medha , Young Lynn , Robison Rex R.
Published: March 2012

The BLAST‐Like Alignment Tool (BLAT) is used to find genomic sequences that match a protein or DNA sequence submitted by the user. BLAT is typically used for searching similar sequences within the same or closely related species. It was developed to align millions of expressed sequence tags and mouse whole‐genome random reads to the human genome at a higher speed. It is freely available either on the Web or as a downloadable stand‐alone program. BLAT search results provide a link for visualization in the University of California, Santa Cruz (UCSC) Genome Browser, where associated biological information may be obtained. Three example protocols are given: using an mRNA sequence to identify the exon‐intron locations and associated gene in the genomic sequence of the same species, using a protein sequence to identify the coding regions in a genomic sequence and to search for gene family members in the same species, and using a protein sequence to find homologs in another species. Curr. Protoc. Bioinform. 37:10.8.1‐10.8.24. © 2012 by John Wiley & Sons, Inc.
Focused actions to protect carbon nanotube workers
Authors: Schulte Paul A. , Kuempel Eileen D. , Zumwalde Ralph D. , Geraci Charles L. , Schubauer‐Berigan Mary K. , Castranova Vincent , Hodson Laura , Murashov Vladimir , Dahm Matthew M. , Ellenbecker Michael
Published: March 2012

There is still uncertainty about the potential health hazards of carbon nanotubes (CNTs) particularly involving carcinogenicity. However, the evidence is growing that some types of CNTs and nanofibers may have carcinogenic properties. The critical question is that while the carcinogenic potential of CNTs is being further investigated, what steps should be taken to protect workers who face exposure to CNTs, current and future, if CNTs are ultimately found to be carcinogenic? This paper addresses five areas to help focus action to protect workers: (i) review of the current evidence on the carcinogenic potential of CNTs; (ii) role of physical and chemical properties related to cancer development; (iii) CNT doses associated with genotoxicity in vitro and in vivo; (iv) workplace exposures to CNT; and (v) specific risk management actions needed to protect workers. Am. J. Ind. Med. 55:395–411, 2012. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.
RNA INTERFERENCE OF TWO ACETYLCHOLINESTERASE GENES IN Plutella xylostella REVEALS THEIR DIFFERENT FUNCTIONS
Authors: He Guiling , Sun Yang , Li Fei
Published: March 2012

Acetylcholinesterase (AChE, EC 3.1.1.7) is an important enzyme with a typical function of degrading the neurotransmitter acetylcholine. Although two ace genes were reported in Plutella xylostella, their function differences remain largely unknown. The chemically synthesized siRNAs (si‐Pxace1 and si‐Pxace2) were injected into the second instar larvae to knock down Pxace1 and Pxace2, either respectively or simultaneously. The mRNA abundance of Pxace1 and Pxace2 was significantly reduced to 7–33.5% of the control levels at 72 h after siRNA injection. The AChE activities were significantly decreased at 96 h after treatment. Silencing of Pxace1 or Pxace2 resulted in mortality of 33.9 and 22.9%, respectively. The survivors in siRNA‐treated groups had apparent growth inhibition such as reduction in larvae weights and lengths, malformation and motor retardation. Knockdown of Pxace1 apparently affected more on larvae growth than that of Pxace2, suggesting that Pxace1 had more important roles than Pxace2. Both Pxace1 and Pxace2 genes might have atypical functions in regulating larvae growth and motor ability.
ANNOTATION AND EVOLUTION OF THE ANTIOXIDANT GENES IN THE SILKWORM, Bombyx mori
Authors: Shi Gui‐Qin , Yu Quan‐You , Zhang Ze
Published: March 2012

Antioxidant system, which is composed of multiple gene families, plays a major role in reducing oxidative damage and xenobiotic detoxification in all living organisms. We identified 50 silkworm antioxidant genes from nine gene families based on the assembled genome sequence. A comparative analysis of the antioxidant genes of the silkworm with other order insects Anopheles gambiae, Apis mellifera, Drosophila melanogaster, and Tribolium castaneum, was performed. We found that most of the antioxidant gene families are highly conserved but Catalase (CAT) and heme‐containing peroxidase (HPX) families were lineage‐specifically expanded in the silkworm. The expression patterns of the silkworm antioxidant genes were investigated with the known ESTs, microarray data, and reverse transcription‐polymerase chain reaction (RT‐PCR). Forty two of the 50 silkworm antioxidant genes were transcribed and most of the transcribed genes showed tissue‐specific expression patterns. More than a half of lineage‐specifically expanded BmCATs lacked 15 or more than 15 of the 36 heme‐binding residues and might lose catalase activities. However, the genes encoding these BmCATs showed almost a ubiquitous tissue expression pattern, indicating that they might have evolved new functions. In addition, the lineage‐specifically expanded BmHPXs could function in maintaining cell homeostasis in the process of the synthesis of large amounts of silk proteins because they were predominantly expressed in silk gland of the silkworm. The lineage‐specific expansion of antioxidant gene families in the silkworm provides useful information for understanding evolution and functional versatility of antioxidant genes in the silkworm even Lepidopteran insects.
Nitrite‐mediated synthesis of chiral epichlorohydrin using halohydrin dehalogenase from Agrobacterium radiobacter AD1
Authors: Jin Huo‐Xi , Hu Zhong‐Ce , Liu Zhi‐Qiang , Zheng Yu‐Guo
Published: March 2012

In the current study, the haloalcohol dehalogenase HheC gene from Agrobacterium radiobacter AD1 was synthesized and expressed in Escherichia coli. After purification using Ni–nitrilotriacetic acid affinity chromatography, HheC was used in the synthesis of chiral epichlorohydrin in the presence of NO2−. The optimal pH, temperature, and NO2− concentration for enantioselectivity are 5.0, 37°C, and 60 mM, respectively. The maximum velocity and Michaelis constant values for (S)‐epichlorohydrin are 714.3 µmol min−1 mg−1 and 17.2 mM, respectively, whereas those for (R)‐epichlorohydrin are 166.8 µmol min−1 mg−1 and 29.0 mM, respectively. Under optimal conditions, (R)‐epichlorohydrin with 99% enantiomeric excess was obtained after an 18 Min reaction; the yield reached 41%, which is the highest amount obtained for chiral epichlorohydrin synthesis using haloalcohol dehalogenase. In addition, (R)‐epichlorohydrin with 99% enantiomeric excess was successfully obtained from 1,3‐dichloro‐2‐propanol by the ring opening of racemic epichlorohydrin in the presence of NO2− after the ring closure of 1,3‐dichloro‐2‐propanol with HheC. To the best of our knowledge, the current study is the first report on the kinetic resolution of epichlorohydrin with NO2− and synthesis of chiral epichlorohydrin with 99% enantiomeric excess from 1,3‐dichloro‐2‐propanol by combining ring closure of 1,3‐dichloro‐2‐propanol and ring opening of racemic epichlorohydrin.
Validation of a Motivation‐based Typology of Angry Aggression among Antisocial Youths in Norway
Authors: Bjørnebekk Gunnar , Howard Rick
Published: March 2012

This article describes the validation of the Angry Aggression Scales (AAS), the Behavior Inhibition System and the Behavior Activation System (BIS/BAS) scales, the reactive aggression and proactive power scales in relation to a Norwegian sample of 101 antisocial youths with conduct problems (64 boys, 37 girls, mean age 15 ± 1.3 years) and 101 prosocial controls matched on age, gender, education, ethnicity, and school district.

Maximum likelihood exploratory factor analyses with oblique rotation were performed on AAS, BIS/BAS, reactive aggression and proactive power scales as well as computation of Cronbach's alpha and McDonald's omega. Tests for normality and homogeneity of variance were acceptable. Factor analyses of AAS and the proactive/reactive aggression scales suggested a hierarchical structure comprising a single higher‐order angry aggression (AA) factor and four and two lower‐order factors, respectively. Moreover, results suggested one BIS factor and a single higher‐order BAS factor with three lower‐order factors related to drive, fun‐seeking and reward responsiveness. To compare scores of antisocial youths with controls, t‐tests on the mean scale scores were computed. Results confirmed that antisocial youths were different from controls on the above‐mentioned scales. Consistent with the idea that anger is associated with approach motivation, AAS scores correlated with behavioral activation, but only explosive/reactive and vengeful/ruminative AA correlated with behavioral inhibition. Results generally validated the quadruple typology of aggression and violence proposed by Howard (2009). Copyright © 2012 John Wiley & Sons, Ltd.
Unusual Phase Evolution in MoVTeNb Oxide Catalysts Prepared by a Novel Acrylamide‐Gelation Route
Authors: Kolen'ko Yury V. , Amakawa Kazuhiko , d'Alnoncourt Raoul Naumann , Girgsdies Frank , Weinberg Gisela , Schlögl Robert , Trunschke Annette
Published: March 2012

The phase evolution of MoVTeNb mixed oxides derived from a novel acrylamide‐gelation approach combined with subsequent washing by hydrogen peroxide and/or annealing in argon was investigated by using powder X‐ray diffraction and scanning electron microscopy in conjunction with energy‐dispersive X‐ray spectroscopy. The calcination of acrylamide‐gelation derived carbon‐based xerogels in air at 410 °C afforded at unexpected low temperature the formation of a phase mixture containing a significant amount of small MoVTeNb oxide crystallites consisting of the M1 phase (ICSD no. 55097). Hydrogen peroxide treatment drastically changed the phase evolution upon annealing in argon at 600 °C. Whereas further enrichment of the M1 phase took place for the untreated precursor, annealing of the washed material resulted in complete collapse of the M1 phase, yielding a ternary MoVNb mixed oxide with tetragonal Mo5O14‐type structure (ICSD no. 27202). The reducing effect of organic residues on phase evolution during calcination of the carbon‐inorganic xerogel in air is discussed. The presence of side phases and the deficiency in tellurium upon annealing have a critical impact on the phase composition of the final product. The catalysts exhibit significant activity in partial oxidation of propane to acrylic acid. The analysis of the product distribution suggested that the activation of both propane and propylene intermediates proceed exclusively over the M1 phase, while side phases do not play a significant role in the reaction.
Molecularly Imprinted Shells from Polymer and Xerogel Matrices on Polystyrene Colloidal Spheres
Authors: Guan Guijian , Liu Renyong , Mei Qingsong , Zhang Zhongping
Published: March 2012

We have devised a facile and general methodology for the synthesis of various molecularly imprinted shells at the surface of polystyrene (PS) colloidal spheres to recognize the explosive compound 2,4,6‐trinitrotoluene (TNT). PS spheres with surface‐functionalized carboxyl‐group layers could direct a selective imprinting polymerization on their surface through the hydrogen‐bonding interactions between surface carboxyl groups and amino monomers. Meanwhile, homogeneous polymerization in the solution phase was completely prevented by stepwise polymerization. The overall process led to the formation of monodisperse molecularly imprinted core–shell microspheres, and was very successful in the preparation of organic polymer and inorganic xerogel shells. Furthermore, greater capacity and faster binding kinetics towards target species were achieved, because surface‐imprinted sites ensured the complete removal of templates, good accessibility to target molecules, and low mass‐transfer resistance. The results reported herein, concerning the production of high‐quality molecularly imprinted products, could also form the basis for the formulation of a new strategy for the fabrication of various functional coating layers on colloidal spheres with potential applications in the fields of separations and chemical sensing.
On the Role of Hydrogen Bonds in Photoinduced Electron‐Transfer Dynamics between 9‐Fluorenone and Amine Solvents
Authors: Ghosh Hirendra N. , Adamczyk Katrin , Verma Sandeep , Dreyer Jens , Nibbering Erik T. J.
Published: March 2012

Using ultrafast fluorescence upconversion and mid‐infrared spectroscopy, we explore the role of hydrogen bonds in the photoinduced electron transfer (ET) between 9‐fluorenone (FLU) and the solvents trimethylamine (TEA) and dimethylamine (DEA). FLU shows hydrogen‐bond dynamics in the methanol solvent upon photoexcitation, and similar effects may be anticipated when using DEA, whereas no hydrogen bonds can occur in TEA. Photoexcitation of the electron‐acceptor dye molecule FLU with a 400 nm pump pulse induces ultrafast ET from the amine solvents, which is followed by 100 fs IR probe pulses as well as fluorescence upconversion, monitoring the time evolution of marker bands of the FLU S1 state and the FLU radical anion, and an overtone band of the amine solvent, marking the transient generation of the amine radical cation. A comparison of the experimentally determined forward charge‐separation and backward charge‐recombination rates for the FLU‐TEA and FLU‐DEA reaction systems with the driving‐force dependencies calculated for the forward and backward ET rates reveals that additional degrees of freedom determine the ET reaction dynamics for the FLU‐DEA system. We suggest that hydrogen bonding between the DEA molecules plays a key role in this behaviour.
An Improved Route to (+)‐Tedanolide and Analysis of Its Subtle Effects Controlling Conformation and Biological Behaviour
Authors: Diaz Nina , Zhu Mingzhao , Ehrlich Gunnar , Eggert Ulrike , Muthukumar Yazh , Sasse Florenz , Kalesse Markus
Published: March 2012

The improved synthesis of the antitumor compound (+)‐tedanolide is described through an aldol coupling of bis‐ketone 7. This modification shortens the synthetic steps in the endgame and provides rapid access to this biologically important natural product. Additionally, it serves as a probe in order to unravel the conformational effects that impede or enable its successful synthesis. Having this way access to des‐epoxy‐tedanolide, its biological characterization surprisingly unravelled the mode of action to resemble candidaspongiolide rather than deoxytedanolide.
A Way to Stable, Highly Emissive Fluorubine Dyes: Tuning the Electronic Properties of Azaderivatives of Pentacene by Introducing Substituted Pyrazines
Authors: Fleischhauer Jan , Zahn Stefan , Beckert Rainer , Grummt Ulrich‐Walter , Birckner Eckhard , Görls Helmar
Published: March 2012

Pentacene and its derivatives are among the most important examples of π‐electron‐rich molecules used in organic field effect transistors. The replacement of CH groups by nitrogen atoms opens an elegant way to generate highly electron‐deficient molecules, known as oligoazaacenes. We describe the synthesis and spectroscopic properties of two novel derivatives of this family, namely the zwitterionic and quinoidal conjugated forms of dihydro‐5,6,7,12,13,14‐hexaazapentacene (fluorubine). We outline a powerful strategy to tune the electronic properties of these redox‐active azaacenes by the selective introduction of substituted pyrazines. Their acidochromic and solvatochromic behaviour is investigated experimentally and interpreted with the help of theoretical calculations. The simple “exchange” of substituents or protonation is shown to significantly alter the spectroscopic and electronic properties of these remarkably stable π‐systems. Their exceptional optical properties, such as high fluorescence quantum yields combined with a redox‐active behaviour, make them promising candidates for sensor materials. Additional marked features in the solid state, such as herringbone packing in combination with short π–π distances, will open access to electronic materials.
Noninvasive Diagnostic Techniques for Coronary Disease in Women
Authors: Vavas Eleni , Hong Susie N. , Rosen Stacey E. , Mieres Jennifer H.
Published: March 2012

Significant advances in medical treatment, medical technology, and the focus on sex‐specific research have contributed to a reduction in cardiovascular mortality in women. Despite these advances, coronary artery disease (CAD) is the leading cause of cardiovascular death of women in the Western world. In the past 2 decades, the focused research on women at risk for CAD has helped to clarify our understanding of some of the sex‐specific factors that are important in the detection of CAD. In women, the detection and evaluation of physiologically significant CAD can be challenging. Many of the traditional tests that are designed to detect focal areas of coronary artery stenosis are less sensitive and specific in female patients, who have a greater burden of symptoms, higher atherosclerotic burden, and lower prevalence of obstructive coronary disease. In this article, we review the available evidence on the role of contemporary noninvasive diagnostic techniques in the evaluation of women with symptoms of CAD.

The authors have no funding, financial relationships, or conflicts of interest to disclose.
Heart Failure in Women
Authors: Shin J. Julia , Hamad Eman , Murthy Sandhya , Piña Ileana L.
Published: March 2012

Heart failure (HF) has steadily increased in prevalence and affects both males and females equally. Despite this, there has been a significant underrepresentation of women in large scale HF trials. This disparity has lead to a deficit in understanding important gender‐based differences in pathophysiology, diagnosis and treatment strategies.

We review these gaps and explore a biological basis for varying outcomes. Endogenous estrogen plays an important role in epidemiology and outcome. The administration of exogenous estrogen has had varied success in treatment and is outlined extensively below. Additionally, we highlight unique HF syndromes through pregnancy and important sex‐specific issues concerning transplant and mechanical circulatory support. A central theme remains: there is a clear need for increased female recruitment in clinical trials, and more studies exploring the role of gender‐based biology in HF treatment. © 2012 Wiley Periodicals, Inc.

The authors have no funding, financial relationships, or conflicts of interest to disclose.
Arrhythmias in Women
Authors: Curtis Anne B. , Narasimha Deepika
Published: March 2012

There are important gender differences in cardiac electrophysiology that affect the epidemiology, presentation, and prognosis of various arrhythmias. Women have been noted to have higher resting heart rates compared to men. They also have a longer QT interval, which puts them at an increased risk for drug‐induced torsades de pointes. Women with atrial fibrillation are at a higher risk of stroke, and they are less likely to receive anticoagulation and ablation procedures compared to men. Women have a lower risk of sudden cardiac death and are less likely to have known coronary artery disease at the time of an event compared to men. Both men and women have been shown to derive an equal survival benefit from implantable cardioverter defibrillators and cardiac resynchronization therapy, although these devices are significantly underutilized in women. Women also appear to have a better response to cardiac resynchronization therapy in terms of reduced numbers of hospitalizations and more robust reverse ventricular remodeling. Further studies are required to elucidate the underlying pathophysiology of these sex differences in cardiac arrhythmias. © 2012 Wiley Periodicals, Inc.

The authors have no funding, financial relationships, or conflicts of interest to disclose.
Hidden Markov Analysis of Trajectories in Single‐Molecule Experiments and the Effects of Missed Events
Authors: Stigler Johannes , Rief Matthias
Published: March 2012

The ever more complex fluctuation patterns discovered by single molecule experiments require statistical methods to analyze multi‐state hopping traces of long lengths. Hidden Markov modeling is a statistical tool that offers the scalability to analyze even complex data and extract kinetic information. We give an introduction on how to implement hidden Markov modeling for the analysis of single molecule force spectroscopic traces, deal with missed events, and test the method on a calcium binding protein.
The Beryllium Pentamer: Trailing an Uneven Sequence of Dissociation Energies
Authors: Ascik Peter N. , Rugango René , Simmonett Andrew C. , Compaan Katherine R. , Schaefer Henry F.
Published: March 2012

Recent high‐resolution spectroscopic studies by Merritt, Bondybey, and Heaven (Science 2009, 324, 1548) have heightened the anticipation that small beryllium clusters will soon be observed in the laboratory. Beryllium clusters are important discrete models for the theoretical study of metals. The trigonal bipyramidal Be5 molecule is studied using high‐level coupled cluster methods. We obtain the optimized geometry, atomization and dissociation energies, and vibrational frequencies. The c∼CCSDT(Q) method is employed to compute the atomization and dissociation energies. In this approach, complete basis set (CBS) extrapolations at the CCSD(T) level of theory are combined with an additive correction for the effect of iterative triple and perturbative quadruple excitations. Harmonic vibrational frequencies are obtained using analytic gradients computed at the CCSD(T) level of theory. We report an atomization energy of 129.6 kcal mol−1 at the trigonal bipyramid global minimum geometry. The Be5→Be4+Be dissociation energy is predicted to be 39.5 kcal mol−1. The analogous dissociation energies for the smaller beryllium clusters are 64.0 kcal mol−1 (Be4→Be3+Be), 24.2 kcal mol−1 (Be3→Be2+Be), and 2.7 kcal mol−1 (Be2→Be+Be). The trigonal bipyramidal Be5 structure has an equatorial–equatorial bond length of 2.000 Å and an axial–equatorial distance of 2.060 Å. Harmonic frequencies of 730, 611, 456, 583, 488, and 338 cm−1 are obtained at the CCSD(T)/cc‐pCVQZ level of theory. Quadruple excitations are found to make noticeable contributions to the energetics of the pentamer, which exhibits a significant level of static correlation.
Chemical Vapor Synthesis and Physico‐chemical Properties of V2O5 Nanoparticles
Authors: Le Hoang Anh , Chin Sungmin , Park Eunseuk , Bae Gwinam , Jurng Jongsoo
Published: March 2012

Vanadium oxides nanoparticles, mainly V2O5, were synthesized by a chemical vapor process using vanadium (V) oxytriethoxide as the precursor. The material synthesis temperatures were varied from 500 to 1300 °C at 200 °C intervals. The physico‐chemical properties of vanadium oxides were analyzed by X‐ray powder diffraction (XRD), transmission electron microscopy (TEM), BET surface area, and X‐ray photoelectron spectroscopy (XPS).
Control of Heteroepitaxial Growth of CaCu3Ti4O12 Films on SrTiO3 Substrates by MOCVD
Authors: Catalano Maria Rita , Malandrino Graziella , Toro Roberta G. , Lo Nigro Raffaella
Published: March 2012

Thin films of CaCu3Ti4O12 (CCTO) are successfully deposited by metal‐organic (MO)CVD on (001)SrTiO3 substrates. An interesting approach, based on a molten multi‐component precursor source, is applied. The molten mixture consists of the Ca(hfa)2•tetraglyme, Ti(tmhd)2(OiPr)2, and Cu(tmhd)2 [Hhfa = 1,1,1,5,5,5‐hexafluoro‐2,4‐pentanedione; tetraglyme = 2,5,8,11,14‐pentaoxapentadecane; Htmhd = 2,2,6,6‐tetramethyl‐3,5‐heptandione; OiPr = iso‐propoxide] precursors. It is also found that, in the present case of a relatively large lattice mismatch (∼5%), the epitaxial growth can be achieved by a careful optimization of deposition parameters. Film structural and morphological characterization is carried out using several techniques; X‐ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). A complete comparison between films deposited by two main processes is carried out in order to understand the kinetic and thermodynamic issues involved in the MOCVD epitaxial growth.
Dynamic channel selection with reinforcement learning for cognitive WLAN over fiber
Authors: Li Yi , Ji Hong , Li Xi , Leung Victor C.M.
Published: March 2012

The Internet of Things (IoT) is the next big possibility and challenge for the future information networks. It makes the interaction between people and things more active and provides the connection among different existing networks. Ubiquitous short‐range wireless access and cognitive radio are key technologies for the IoT's realization. This paper deals with some problems in an integrated system of wireless local area network (WLAN) and cognitive radio — cognitive WLAN over fiber (CWLANoF). CWLANoF is a cost‐effective and efficient architecture that combines radio over fiber and cognitive radio technologies to provide centralized radio resource management and equal spectrum access in infrastructure‐based IEEE 802.11 WLANs. In this paper, a reinforcement learning approach is applied to implement dynamic channel selection in CWLANoF. The cognitive access points select the best channels among the industrial, scientific, and medical band for data packet transmission, given that the objective is to minimize external interference and acquire better network‐wide performance. The reinforcement learning method avoids solving complex optimization problems while being able to explore the states of a CWLANoF system during normal operations. Simulation results reveal that the proposed strategy is effective in avoiding aggregated interference, reducing outage probability, and improving network throughput. Copyright © 2012 John Wiley & Sons, Ltd.
Allopurinol attenuates left ventricular dysfunction in rats with early stages of streptozotocin‐induced diabetes
Authors: Gao Xia , Xu Yuan , Xu Bo , Liu Yanan , Cai Jun , Liu Hui‐min , Lei Shaoqing , Zhong Yin‐qin , Irwin Michael G. , Xia Zhengyuan
Published: March 2012

Background

Xanthine oxidase‐derived superoxide production and oxidative stress contribute to the development of diabetic complications including diabetic cardiomyopathy. We hypothesized that xanthine oxidase‐inhibitor allopurinol (ALP) may decrease hyperglycemia‐induced oxidative stress, ameliorate cardiomyocyte hypertrophy and fibrosis, and attenuate the development of left ventricle (LV) diastolic dysfunction in rats with streptozotocin (STZ)‐induced diabetes.

Methods

Control Sprague Dawley (C) or streptozotocin‐induced diabetic (D) rats were either untreated or treated with allopurinol (100 mg/kg/day) for 4 weeks starting at 1 week after streptozotocin injection. Free 15‐F2t‐isoprostane, a specific indicator of oxidative stress was measured by enzymatic immunoassay. The cardiomyocyte cross‐sectional area was assessed by hematoxylin and eosin‐stained paraffin‐embedded sections of LVs. Myocardial collagens I and III were assessed by immunol histochemistry and Western blotting. Echocardiography was performed to characterize cardiac structure and function.

Results

In diabetic rats, both plasma and cardiac tissue levels of free 15‐F2t‐isoprostane were increased (p < 0.05 vs. control), accompanied with significant increase (p < 0.05 vs. control) in cross‐section area and myocardial collagen deposition of LV cardiomyocyte. Echocardiography in diabetic rats showed that LV weight/body weight ratio was significantly higher than in control rats, whereas the levels of LV end‐diastolic volume and stroke volume were decreased (all p < 0.05 diabetic vs. control). All these changes were either attenuated or prevented by allopurinol. In addition, LV ejection fraction in diabetic rats treated with allopurinol was higher than that in untreated diabetic rats (p < 0.05).

Conclusion

Allopurinol can attenuate hyperglycemia‐induced oxidative stress, ameliorate cardiomyocyte hypertrophy and fibrosis and subsequently prevent left ventricular dysfunction in early diabetes. Copyright © 2012 John Wiley & Sons, Ltd.
Major antioxidant constituents from Satureja hortensis L. extracts obtained with different solvents
Authors: Plánder Szabina , Gontaru Lenuta , Blazics Balázs , Veres Katalin , Kéry Ágnes , Kareth Sabine , Simándi Béla
Published: March 2012

Analysis of different extracts of Satureja hortensis L. obtained with various solvents (by supercritical CO2 and by traditional extraction techniques) is presented in this study to identify and to determine the major constituents responsible for the antioxidant activity. The total polyphenol and total flavonoid contents of the extracts were determined by spectrophotometric method and no correlation was found with the antioxidant activites. HPLC was also used to measure two diterpenes as carnosol and carnosic acid in the extracts. Neither carnosol nor carnosic acid were identified. Individual antioxidants as rosmarinic and caffeic acids were identified and quantified with TLC‐densitometry method. Rosmarinic acid was found in higher amount than caffeic acid. The content of rosmarinic acid was also determined with HPLC. A good correlation coefficient of 0.85 was found between the antioxidant activity and amount of rosmarinic acid, which leads to the conclusion that rosmarinic acid is among the main antioxidant compounds of S. hortensis L. plant.
Generation of Stereocenters Around a C3‐Symmetric Cyclotriveratrylene Crown
Authors: Sansévérino Julien , Aubert Emmanuel , Espinosa Enrique , Chambron Jean‐Claude
Published: March 2012

The oxidation of racemic methylthio‐substituted C3‐symmetric cyclotriveratrylene (CTV) 2 produces the corresponding trisulfoxides 3 as follows. Oxidation with m‐chloroperoxybenzoic acid (m‐CPBA) in dichloromethane leads to the formation of a distribution of the four possible diastereomers that is relatively close to the statistical outcome, in which the C3‐symmetric stereoisomers are the minor species. In contrast, the optically active Davis reagent [oxaziridine (+)‐4] in carbon tetrachloride at room temperature leads to a biased (73 %) distribution in favor of the C3‐symmetric MRRR/PSSS diastereomer of 3 with 56 % ee (PSSS enantiomer according to the model of Davis). Interestingly, when the oxidation is carried out in toluene at reflux, the distribution is switched to approximately equal amounts of the C3‐symmetric MSSS/PRRR and asymmetric MRSS/PSRR diastereomers of 3. Overall, however, these results point to the negligible role played by the chirality of the CTV platform on the induction of chirality at the sulfur prochiral centers.
In ovo exposure to nonylphenol and bisphenol A resulted in dose-independent feminization of male gonads in Japanese quail (Coturnix japonica) embryos
Authors: Oshima Atsushi , Yamashita Ryo , Nakamura Keigo , Wada Masaru , Shibuya Kazumoto
Published: March 2012

Sex reversal effects of nonylphenol and bisphenol A on the gonads in F1(AWE × WE) Japanese quail (Coturnix japonica) embryos were investigated using an in vivo screening model developed previously. The F1 (AWE × WE) Japanese quail are a useful avian model because sex differentiation is confirmed by the plumage color before hatching, ruled by a criss-cross inheritance. The nonylphenol at 200, 2,000, 20,000, and 200,000 ng/egg and bisphenol A at 20, 200, 2,000, and 20,000 ng/egg were injected into the egg white just before incubation. At 16 d of incubation, embryos were subjected to a complete necropsy, and their gonads were both grossly observed and examined histopathologically and morphometrically. Grossly, genetic sex was confirmed because plumage color coincided completely with the external sex phenotype of the gonads in all embryos. Histopathologically, feminization of the male gonad, called ovotestis, developed in the left testis in all nonylphenol- and bisphenol A-treated groups. The incidence of the lesion in all treated groups was significantly higher than that in the control group, whereas there were no dose-dependent changes in the incidence and area of the ovotestis in both nonylphenol- and bisphenol A-treated groups. The present study revealed that nonylphenol and bisphenol A have a dose-independent potential of ovotestis induction in the Japanese quail embryo. Environ. Toxicol. Chem. 2012; 31: 1091–1097. © 2012 SETAC
Feminization and altered gonadal gene expression profile by ethinylestradiol exposure to pejerrey, Odontesthes bonariensis, a South American teleost fish
Authors: Pérez María R. , Fernandino Juan I. , Carriquiriborde Pedro , Somoza Gustavo M.
Published: March 2012

In pejerrey (Odontesthes bonariensis), ovarian differentiation has been associated with gonadal aromatase expression. It is also known that exposure of pejerrey larvae to estradiol (E2) produces all female populations. During the last few years, the presence of ethinylestradiol (EE2), a synthetic E2 analogue, has been reported in water reservoirs of different parts of the world. In the present study, the effects of EE2 were assessed on sex ratio bias and gene expression levels of gonadal aromatase (cyp19a1a), 11β-hydroxysteroid dehydrogenase type 2 (hsd11b2), estrogens (erα, erβ1), and androgen receptors (arα, arβ). Pejerrey larvae were fed with commercial food containing EE2 (0.1 and 1 µg/g) and E2 (50 µg/g) as a positive control for six weeks after hatching. The gonadal histological analysis showed that 42 to 46% of the fish had clearly differentiated ovaries in both the EE2- and E2-treated groups, compared with 27% in the control group. Moreover, in the EE2- (1 µg/g) and E2-treated groups, no fish presented signs of testicular development compared with controls. In addition, expression of cyp19a1a and hsd11b2 was significantly up- and downregulated, respectively, by EE2 and E2. The authors' results suggested that the feminization process driven by EE2 depends on the positive balance of cyp19a1a in relation to hsd11b2. Thus, these genes can be used as early indicators of exposure to xenoestrogens in this species. Environ. Toxicol. Chem. 2012; 31: 941–946. © 2012 SETAC
The effects of multitasking on psychological stress reactivity in recreational users of cannabis and MDMA
Authors: Wetherell Mark A. , Atherton Katie , Grainger Jessica , Brosnan Robert , Scholey Andrew B.
Published: March 2012

Background

Cannabis and 3,4‐methylenedioxymethamphetamine (MDMA) use is associated with psychobiological and neurocognitive deficits. Assessments of the latter typically include tests of memory and everyday cognitive functioning. However, to date, little attention has been paid to effects of drug use on psychological stress reactivity. We report three studies examining the effects of recreational use of cannabis and MDMA on mood and psychological responses to multitasking using a cognitively demanding laboratory stressor that provides an analogue for everyday situations involving responses to multiple stimuli.

Methods

The effects of the multitasking framework on mood and perceived workload were assessed in cannabis (N=25), younger (N=18) and older (N=20) MDMA users and compared with non‐target drug controls.

Results

Compared with respective control groups, cannabis users became less alert and content, and both MDMA groups became less calm following acute stress. Unexpectedly, the stressor increased ratings of calm in cannabis users. Users also scored higher than their controls with respect to ratings of resources needed to complete the multitasking framework.

Conclusions

These findings show, for the first time, that recreational use of cannabis and MDMA, beyond the period of intoxication, can negatively influence psychological responses to a multitasking stressor, and this may have implications for real‐life situations which place high demands on cognitive resources. Copyright © 2012 John Wiley & Sons, Ltd.
Hillslope‐scale probabilistic characterization of soil moisture dynamics and average water balance
Authors: Pan Xingyao , Potter Nicholas J. , Xia Jun , Zhang Lu
Published: March 2012

Probabilistic water balance modelling provides a useful framework for investigating the interactions between soil, vegetation, and the atmosphere. It has been used to estimate temporal soil moisture dynamics and ecohydrological responses at a point. This study combines a nonlinear rainfall–runoff theory with probabilistic water balance model to represent varied source area runoff as a function of rainfall depth and a runoff coefficient at hillslope scale. Analytical solutions of the soil‐moisture probability density function and average water balance model are then developed. Based on a sensitivity analysis of soil moisture dynamics, we show that when varied source area runoff is incorporated, mean soil moisture is always lower and total runoff higher, compared with the original probabilistic water balance model. The increased runoff from the inclusion of varied source area runoff is mainly because of a reduction in leakage when the index of dryness is less than one and evapotranspiration when the index of dryness is greater than one. Inclusion of varied source area runoff in the model means that the actual evapotranspiration is limited by less available water (i.e. water limit), which is stricter than Budyko’s and Milly’s water limit. Application of the model to a catchment located in Western Australia showed that the method can predict annual value of actual evapotranspiration and streamflow accurately. Copyright © 2012 John Wiley & Sons, Ltd.
Groundwater responses to the 2011 Tohoku Earthquake on Jeju Island, Korea
Authors: Lee Soo‐Hyoung , Ha Kyoochul , Hamm Se‐Yeong , Ko Kyung‐Seok
Published: March 2012

Groundwater responses at 15 monitoring wells on Jeju Island were observed in relation to the magnitude 9.0 Tohoku Earthquake off the Pacific coast of Honshu, Japan, on 11 March 2011, at 14:46:23 h local time (05:46:24 h UTC time). In coastal areas, the groundwater level responses to the earthquake were oscillatory at 12 wells, and the range of the maximum groundwater level changes was 3–192.4 cm. The response durations were approximately 1–62 min. The relationship between the maximum groundwater level changes and the response durations displayed a high correlation coefficient (r = 0.81). Groundwater temperature changes were also observed at 7 of 12 wells 3–10 min after the seismic wave arrived, and the range was from 0.01 °C to 1.20 °C. In mid‐elevation areas, the groundwater level changes appeared in three different forms: oscillatory, spiky and persistent. The groundwater temperature changes were also observed at two wells. One indicated decreasing and recovering temperatures, and the other exhibited rising and persistent temperatures. The primary temperature changes occurred 5–6 min after the earthquake and 2–3 min after the seismic wave arrived. In addition, the electrical conductivities at the depth of the transition zone were monitored, and the responses to the earthquake appeared at all three wells. Although the electrical conductivity and temperature changes were not well understood, groundwater inflow and mixing were likely caused by the earthquake, and the responses were various and site specific. The responses to the earthquake were closely related to the hydrogeological characteristics at each monitoring well, and a more detailed hydrogeological characterization is needed to understand the mechanisms related to earthquakes in general. Copyright © 2012 John Wiley & Sons, Ltd.
Endothelial cell responses to micropillar substrates of varying dimensions and stiffness
Authors: Dickinson Laura E. , Rand Danielle R. , Tsao Joanna , Eberle Wolfgang , Gerecht Sharon
Published: March 2012

In the vascular niche, the extracellular matrix (ECM) provides a structural scaffold with a rich ligand landscape of essential matrix proteins that supports the organization and stabilization of endothelial cells (ECs) into functional blood vessels. Many of the physical interactions between ECs and macromolecular components of the ECM occur at both the micron and submicron scale. In addition, the elasticity of the ECM has been shown to be a critical factor in the progress of the angiogenic cascade. Here, we sought to determine the effect of substrate topography and elasticity (stiffness) on EC behavior. Utilizing a unique SiO2 substrate with an array of micropillars, we first demonstrate that micropillars with heights >3 μm significantly decrease EC adhesion and spreading. Fibronectin (Fn) patterning of 1 μm high micropillars enabled EC adhesion onto the micropillars and promoted alignment in a single‐cell chain manner. We then developed a robust method to generate a soft micropillar substrate array made of polydimethylsiloxane (PDMS), similar to the SiO2 substrate. Finally, we examined the kinetics of EC adhesion and spreading on the soft PDMS substrates compared to the stiff SiO2 substrates. Culturing cells on the PDMS substrates demonstrated an enhanced EC elongation and alignment when compared to stiff SiO2 with similar topographical features. We conclude that the elongation and alignment of ECs is coregulated by substrate topography and stiffness and can be harnessed to guide vascular organization. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.
TSA‐induced JMJD2B downregulation is associated with cyclin B1‐dependent survivin degradation and apoptosis in LNCap cells
Authors: Zhu Shan , Li Yueyang , Zhao Li , Hou Pingfu , Shangguan Chenyan , Yao Ruosi , Zhang Weina , Zhang Yu , Tan Jiang , Huang Baiqu , Lu Jun
Published: March 2012

Histone deacetylase (HDAC) inhibitors are emerging as a novel class of anti‐tumor agents and have manifested the ability to induce apoptosis of cancer cells, and a significant number of genes have been identified as potential effectors responsible for HDAC inhibitor‐induced apoptosis. However, the mechanistic actions of these HDAC inhibitors in this process remain largely undefined. We here report that the treatment of LNCap prostate cancer cells with HDAC inhibitor trichostatin A (TSA) resulted in downregulation of the Jumonji domain‐containing protein 2B (JMJD2B). We also found that the TSA‐mediated decrease in survivin expression in LNCap cells was partly attributable to downregulation of JMJD2B expression. This effect was attributable to the promoted degradation of survivin protein through inhibition of Cyclin B1/Cdc2 complex‐mediated survivin Thr34 phosphorylation. Consequently, knockdown of JMJD2B enhanced TSA‐induced apoptosis by regulating the Cyclin B1‐dependent survivin degradation to potentiate the apoptosis pathways. J. Cell. Biochem. 113: 2375–2382, 2012. © 2012 Wiley Periodicals, Inc.
Changes in serum collagen markers, IGF‐I, and Knee joint laxity across the menstrual cycle
Authors: Shultz Sandra J. , Wideman Laurie , Montgomery Melissa M. , Beasley Kathleen N. , Nindl Bradley C.
Published: March 2012

Variations in serum markers of collagen production (CICP) and degradation (ICTP), insulin‐like growth factor I (IGF‐I) and anterior knee laxity (AKL) were measured in 20 women [10 with spontaneous cycles (eumenorrheic), 10 using oral contraceptives] over 5 consecutive days at menses (M1–M5, 1st pill week), the initial estrogen rise near ovulation (O1–O5, 2nd pill week), the initial progesterone rise of the early luteal phase (EL1–EL5, 3rd pill week) and post‐progesterone peak of the late luteal phase (LL1–LL5, 4th pill week). ICTP was higher in oral contraceptive women (5.3 ± 1.7 vs. 3.7 ± 1.3 µg/L; p = 0.030), primarily during days near ovulation and the early luteal phase when concentrations decreased in eumenorrheic women (p = 0.04). IGF‐I concentrations increased during menses then decreased and remained lower during the early and late luteal phase in oral contraceptive women, resulting in lower concentrations compared to eumenorrheic women at EL2 and LL1 (p = 0.03). CICP decreased in early and late luteal days (p <0.01), and there was a trend toward lower concentrations in eumenorrheic versus oral contraceptive women (85.7 ± 35.7 ng/ml vs. 123.2 ± 49.8 ng/ml; p = 0.07). Lower CICP and greater IGF‐I concentrations predicted greater AKL across the 20 cycle days in both groups (R2 = 0.310 and 0.400). Sex hormone concentration changes across the menstrual cycle are of sufficient magnitude to influence collagen metabolism, and may indirectly influence knee structure and function. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1405–1412, 2012
Frequency, clinical presentation, and outcomes of drug-induced liver injury after liver transplantation
Authors: Sembera Stepan , Lammert Craig , Talwalkar Jayant A. , Sanderson Schuyler O. , Poterucha John J. , Hay Eileen J. , Wiesner Russell H. , Gores Gregory J. , Rosen Charles B. , Heimbach Julie K. , Charlton Michael R.
Published: March 2012

Drug-induced liver injury (DILI) is increasingly being recognized as a common cause of acute hepatitis. The clinical impact of DILI after liver transplantation (LT) is not known. The aim of this study was to describe the frequency, clinical presentation, and outcomes of DILI in LT recipients. LT recipients with possible DILI were identified with electronic pathology records and clinical note database retrieval tools. Diagnostic criteria were applied to identify cases of DILI. Twenty-nine of 1689 LT recipients (1.7%) were identified with DILI. The mean age was 52 years, and 52% were women. The major indications for LT were primary sclerosing cholangitis (28%), cholangiocarcinoma (14%), and hepatocellular carcinoma (14%). The severity of DILI was mild or moderate in 92% of the cases. Nausea or diarrhea (31%), jaundice (24%), and pruritus (10%) were the most common symptoms at the time of diagnosis. The mean biochemistry values were as follows: alanine aminotransferase, 204 ± 263 U/L; aspartate aminotransferase, 108 ± 237 U/L; alkaline phosphatase, 469 ± 689 U/L; and total bilirubin, 1.9 ± 10.3 mg/dL. The median duration of medication use until the diagnosis of DILI was 57 days, and the major agent classes were antibiotics (48%), immunosuppressive agents (14%), and antihyperlipidemic drugs (7%). Trimethoprim-sulfamethoxazole was the most common implicated agent (n = 11). Serum liver enzymes improved within a median time of 34 days (range = 5–246 days) after drug withdrawal. Hepatic retransplantation or death did not occur. Among the 50 cases with possible DILI explained by other causes, 13 individuals (26%) had no alternative diagnosis despite histological findings compatible with DILI. In conclusion, DILI is a rare yet underrecognized event among LT recipients. The majority of cases are not clinically severe, and they resolve after drug cessation without hepatic retransplantation or death. Liver Transpl, 2012. © 2012 AASLD.