bluuebunny/crossref_metadata_2025 huggingface dataset:
A new fluorescence complementation biosensor for detection of estrogenic compounds
Authors: McLachlan Michael J. , Katzenellenbogen John A. , Zhao Huimin
Published: July 2011

Estrogenic compounds are an important class of hormonal substances that can be found as environmental contaminants, with sources including pharmaceuticals, human and animal waste, the chemical industry, and microbial metabolism. Here we report the creation of a biosensor useful for monitoring such compounds, based on complementation of fluorescent protein fragments. A series of sensors were made consisting of fragments of a split mVenus fluorescent protein fused at several different N‐terminal and C‐terminal positions flanking the ligand binding domain of the estrogen receptor alpha. When expressed in HeLa cells, sensor 6 (ERα 312‐595) showed a nine‐fold increase in fluorescence in the presence of estrogen receptor agonists or antagonists. Sensor 2 (ERα 281‐549) discriminated between agonists and antagonists by showing a decrease in fluorescence in the presence of agonists while being induced by antagonists. The fluorescent signal of sensor 6 increased over a period of 24 h, with a two‐fold induction visible at 4 h and four‐fold at 8 h of ligand incubation. Ligand titration showed a good correlation with the known relative binding affinities of the compound. The sensor could detect a number of compounds of interest that can act as environmental endocrine disruptors. The lack of a substrate requirement, the speed of signal development, the potential for high throughput assays, and the ability to distinguish agonists from antagonists make this an attractive sensor for widespread use. Biotechnol. Bioeng. 2011;108: 2794–2803. © 2011 Wiley Periodicals, Inc.
Design and Synthesis of Iridium Bis(carbene) Complexes for Efficient Blue Electrophosphorescence
Authors: Hsieh Cheng‐Han , Wu Fang‐Iy , Fan Chun‐Hsiang , Huang Min‐Jie , Lu Kun‐Yi , Chou Pei‐Yu , Yang Yu‐Han Ou , Wu Shih‐Hsiang , Chen I‐Chia , Chou Shu‐Hua , Wong Ken‐Tsung , Cheng Chien‐Hong
Published: July 2011

Five iridium bis(carbene) complexes, [Ir(pmi)2(pypz)] (1), [Ir(mpmi)2(pypz)] (2), [Ir(fpmi)2(pypz)] (3), [Ir(fpmi)2(pyim)] (4), and [Ir(fpmi)2(tfpypz)] (5) (pmi=1‐phenyl‐3‐methylimdazolin‐2‐ylidene‐C,C2′; fpmi=1‐(4‐fluorophenyl)‐3‐methylimdazolin‐2‐ylidene‐C,C2′; mpmi=1‐(4‐methyl‐phenyl)‐3‐methylimdazolin‐2‐ylidene‐C,C2′; pypz=2‐(1H‐pyrazol‐5‐yl)pyridinato; pyim=2‐(1H‐imidazol‐2‐yl)pyridinato; and tfpypz=2‐(3‐(trifluoromethyl)‐1H‐pyrazol‐5‐yl)pyridinato), were synthesized and their structures were characterized by NMR spectroscopy, mass spectroscopy and X‐ray diffraction. These complexes showed phosphorescent emission with the emission maxima between 453 and 490 nm. Various spectrophotometric measurements, cyclic voltammetric studies, and density functional theory (DFT) calculations show that, unlike most of the phosphorescent cyclometalated iridium complexes, the lowest unoccupied molecular orbital (LUMO) energy and the emissive state of these iridium complexes are mainly controlled by the N,N′‐heteroaromatic (N^N) ligand. Despite the fact that the LUMO levels of these complexes are mainly on the N^N ligands, the efficiencies of the electroluminescent (EL) devices are very high. For example, the EL devices using [Ir(mpmi)2(pypz)], [Ir(fpmi)2(pypz)], and [Ir(fpmi)2(tfpypz)] as the dopant emitters exhibited light‐ to deep‐blue electrophosphorescence with external quantum efficiencies of 15.2, 14.1, and 7.6 % and Commission Internationale d’Énclairage (x,y) coordinates (CIEx,y) of (0.14, 0.27), (0.14, 0.18) and (0.14, 0.10), respectively.
Theoretical and X‐ray Crystallographic Evidence of a Fluorine‐Imine Gauche Effect: An Addendum to Dunathan’s Stereoelectronic Hypothesis
Authors: Sparr Christof , Salamanova Evdokiya , Schweizer W. Bernd , Senn Hans Martin , Gilmour Ryan
Published: July 2011

The preference of β‐fluoroimines to adopt a gauche conformation has been studied by single‐crystal X‐ray diffraction analysis and DFT methods. Empirical and theoretical evidence for a preferential gauche arrangement around the NCCF torsion angle (ϕ) is presented ((E)‐2‐fluoro‐N‐(4‐nitrobenzylidene)ethanamine: ϕNCCF=70.0°). In the context of this study, the analysis of a pyridoxal‐derived β‐fluoroaldimine was performed, a species that is implicated in the inhibition of pyridoxal phosphate (PLP)‐dependent enzymes by β‐fluoroamine derivatives. The gauche preference of the internal aldimine (=NCH2CH2F) that can be rationalized by stereoelectronic arguments does not hold for the corresponding external system (NCHCH2F) (Emin when ϕNCCF=120°). Moreover, the CF bond is lengthened by more than 0.02 Å at ϕNCCF=±90°, when it is exactly antiperiplanar to the conjugated imine. This activation of the CF σ bond by an adjacent π system constitutes an addendum to Dunathan’s stereoelectronic hypothesis.
Tissue Uptake Study and Photodynamic Therapy of Melanoma‐Bearing Mice with a Nontoxic, Effective Chlorin
Authors: Dąbrowski Janusz M. , Krzykawska Martyna , Arnaut Luis G. , Pereira Mariette M. , Monteiro Carlos J. P. , Simões Sérgio , Urbańska Krystyna , Stochel Grażyna
Published: July 2011

Chlorins have intense red absorptions and high tumor affinities that make them interesting candidates for photodynamic therapy (PDT) of cancer. This paper reports cytotoxicity, phototoxicity, in vitro cellular uptake, and in vivo biodistribution and PDT efficacy of a synthetic chlorin derivative (TCPCSO3H) towards Cloudman melanoma cells (S91). No cytotoxic effects were observed in vitro at concentrations up to 20 μm, and no toxicity was observed in vivo in DBA mice with doses up to 2 mg kg−1. Pharmacokinetics and biodistribution of TCPCSO3H were evaluated in vivo in DBA mice bearing S91 tumors. TCPCSO3H demonstrated preferential accumulation in S91 mouse melanoma, with tumor‐to‐normal tissue ratios of 5 and 11 for muscle and skin, respectively, 24 h after intravenous injection of 2 mg kg−1. Photodynamic therapy performed under these conditions with 70 mW cm−2 diode laser irradiation at 655 nm for 25 min (total light dose=105 J cm−2) resulted in scab formation, followed by temporary or permanent (>60 days) tumor remission. According to the Kaplan–Meier analysis, the median survival time of the control group was 9 days, whereas that of the treated group was 38 days.
Ultrafast Electron Transfer from Photoexcited CdSe Quantum Dots to Methylviologen
Authors: Scholz Frank , Dworak Lars , Matylitsky Victor V. , Wachtveitl Josef
Published: July 2011

The ultrafast charge separation at the quantum dot (QD)/molecular acceptor interface was investigated in terms of acceptor concentration and the size of the QD. Time‐resolved experiments revealed that the electron transfer (ET) from the photoexcited QD to the molecular acceptor methylviologen (MV2+) occurs on the fs time scale for large acceptor concentrations and that the ET rate is strongly reduced for low concentrations. The increase in the acceptor concentration is accompanied with a growth in the overlap of donor and acceptor wavefunctions, resulting in a faster reaction until the MV2+ concentration reaches a saturation limit of 0.3–0.4 MV2+ nm−2. Moreover, we found significant QD size dependence of the ET reaction, which is explained by a change of the free energy (ΔG).
Recent Progress on the Growth Mechanism of Carbon Nanotubes: A Review
Authors: Tessonnier Jean‐Philippe , Su Dang Sheng
Published: July 2011

Tremendous progress has been achieved during the past 20 years on not only improving the yields of carbon nanotubes and move progressively towards their mass production, but also on gaining a profound fundamental understanding of the nucleation and the growth processes. Parameters that influence the yield but also the quality (e.g., microstructure, homogeneity within a batch) are better understood. The influence of the carbon precursor, the reaction conditions, the presence of a catalyst, the chemical and physical status of the latter, and other factors have been extensively studied. The purpose of the present Review is not to list all the experiments reported in the literature, but rather to identify trends and provide a comprehensive summary on the role of selected parameters. The role of the catalyst occupies a central place in this Review as a careful control of the metal particle size, particle dispersion on the support, the metastable phase formed under reaction conditions, its possible reconstruction, and faceting strongly influence the diameter of the carbon nanotubes, their structure (number of walls, graphene sheet orientation, chirality), their alignment, and the yield. The identified trends will be compared with recent observations on the growth of graphene. Recent results on metal‐free catalysts will be analyzed from a different perspective.
Voltammetric Determination of Hemoglobin Using a Pencil Lead Electrode
Authors: Majidi Mir Reza , Saadatirad Afsaneh , Alipour Esmaeel
Published: July 2011

In this paper the electrochemical behavior of hemoglobin (Hb) immobilized on a pencil lead electrode (PLE) was investigated. Immobilization of Hb on the pencil lead electrode was performed by nonelectrochemical and electrochemical methods. In phosphate buffer solution with pH 7.0 Hb showed a pair of well‐defined and nearly reversible redox waves (the anodic and cathodic peak potentials are located at −0.18 V and −0.22 V, respectively). The dependence of the anodic peak potential (Epa) on the pH of the buffer solution indicated that the conversion of HbFe(III)/HbFe(II) is a one‐electron‐transfer reaction process coupled with one‐proton‐transfer. In addition the effect of scan rate on peak currents and peak separation potential was investigated and electrochemical parameters such as α and ks were calculated. In the second part of this work, the ability of the electrode for determination of Hb concentration was investigated. The results showed a linear dynamic range from 0.15 to 2 µM and a detection limit of 0.11 µM. The relative standard deviation is 4.1 % for 4 successive determinations of a 1 µM Hb solution.
Amperometric Ethanol Biosensors Based on Chitosan‐NAD+‐Alcohol Dehydrogenase Films
Authors: Zhang Maogen , Gorski Waldemar
Published: July 2011

The reagentless and oxygen‐independent biosensors for ethanol were developed based on the covalent immobilization of alcohol dehydrogenase (ADH) and its cofactor nicotinamide adenine dinucleotide (NAD+) on chitosan (CHIT) chains. The CHIT‐NAD+‐ADH structures were adsorbed onto carbon nanotubes (CNT) in order to provide a signal transduction based on the recycling of redox states of NAD cofactor at CNT (detection limit, 8–30 µM ethanol; dynamic range up to 20 mM). The CHIT‐NAD+‐dehydrogenase/CNT hybrid material represents a general approach to the development of dehydrogenases‐based electrochemical biosensors. Interestingly, the CHIT‐NAD+ solutions preserved their enzymatic activity even after five years of storage at 4 °C.
An individual-based modeling approach for evaluation of endpoint sensitivity in harpacticoid copepod life-cycle tests and optimization of test design
Authors: Preuss Thomas G , Brinkmann Markus , Lundström Elin , Bengtsson Bengt-Erik , Breitholtz Magnus
Published: July 2011

In the present study, an individual-based model for Nitocra spinipes was developed and used to optimize the test design of a proposed Organisation for Economic Co-operation and Development test guideline for harpacticoid copepods. The variability between individuals was taken into account, based on measured data, leading to stochastic model output. Virtual experiments were performed with the model to analyze the endpoint sensitivity and the effect of number of replicates and inspection intervals on statistical power. The impact of mortality was evaluated; most sublethal effects could not be determined if the mortality was ≥70%. Most sensitive to mortality was the determination of effects on brood size, for which the statistical power was reduced at 10% mortality. Our simulations show that increasing the number of replicates from 72 to 96 or 144 has little impact on the statistical power, whereas 25 replicates disallow relevant endpoint detection. Furthermore, it was demonstrated that the proposed 1D inspection interval can be shifted to a 3D interval, without losing statistical power. It was demonstrated that developmental endpoints have a higher statistical power than reproductive endpoints in the current test design. The present study highlights the usefulness of individual-based models for optimizing the experimental design. The use of such models in the development of standard test guidelines will lead to a faster and less resource-demanding process. Environ. Toxicol. Chem. 2011;30:2353–2362. © 2011 SETAC
Has the introduction of S&P 500 ETF options led to improvements in price discovery of SPDRs?
Authors: Chen Wei‐Peng , Chung Huimin
Published: July 2011

This study sets out to investigate trading in Standard and Poor's Depository Receipt Trust Series I (SPDR) options and the impact on the price‐discovery process of SPDRs. The empirical results reveal a significant rise in liquidity within the SPDR market following the introduction of SPDR options. Furthermore, the results also show that the introduction of SPDR options has led to a significant improvement in the information share of SPDRs, and that the contribution of SPDRs to price discovery has become very close to that of E‐mini index futures. These findings imply that developments in the derivatives market can lead to improvements in market quality, including the level of liquidity and price discovery of the underlying securities. © 2011 Wiley Periodicals, Inc. Jrl Fut Mark 32:683–711, 2012
Biomarkers in dementia with Lewy bodies: a review
Authors: Sinha Namrta , Firbank Michael , O'Brien John T.
Published: July 2011

Background

Dementia with Lewy bodies (DLB) shares common clinical, neuropsychological and pathological features with other dementia subtypes, such as Alzheimer's disease (AD), making it difficult to differentiate in clinical practice. Despite the development of consensus diagnostic criteria, many cases are missed, and biomarkers to assist with diagnosis would represent important advances. Our aim was to review the literature to identify potential biomarkers that may distinguish DLB from other dementia subtypes, especially AD.

Method

The literature search was performed using Medline up to October 2010 for imaging studies [single‐photon emission computed tomography (SPECT), positron emission tomography (PET), magnetic resonance imaging (MRI) and amyloid imaging] and cerebrospinal fluid (CSF) markers in DLB. Individual articles were examined for additional references. The abstracts of the identified articles were read to determine the most relevant papers, which became the basis for this review.

Results

The most robust evidence available was for striatal dopamine transporter activity visualised by 123I‐labelled N‐(3‐fluoropropyl)‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)nortropane (123I‐FP‐CIT) SPECT. Several other imaging techniques have also reported promising results, such as [18F]fluorodopa PET, which assesses nigrostriatal integrity; [18F]fluorodeoxyglucose PET, which assesses metabolic deficits; and meta‐iodobenzylguanidine imaging, which assesses sympathetic cardiac denervation. Data from studies using CSF measures of amyloid and tau, occipital hypoperfusion on SPECT and preservation of medial temporal lobe structures on MRI suggest that they may offer less diagnostic discrimination.

Conclusion

Several potential biomarkers have shown good diagnostic accuracy for DLB, but apart from FP‐CIT SPECT, there is now a need for larger clinical multi‐site studies, as well as for studies with pathological verification of diagnosis, before their use could be recommended for routine clinical practice. Copyright © 2011 John Wiley & Sons, Ltd.
Generation of pyrrolo[2,1‐a]isoquinoline derivatives from N‐ylides: Synthetic control and structural characterization
Authors: Dumitrascu Florea , Caira Mino R. , Georgescu Emilian , Georgescu Florentina , Draghici Constantin , Popa Marcel Mirel
Published: July 2011

New pyrrolo[2,1‐a]isoquinolines were obtained by two one‐pot procedures via 1,3‐dipolar cycloaddition between the isoquinolinium N‐ylides and symmetrical acetylenic dipolarophiles, avoiding the formation of dihydro intermediates. For structural comparison, the dihydro derivatives obtained by a classical two‐stage reaction were characterized by NMR and X‐ray crystallography, allowing complete stereochemistry assignments. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:723–729, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/.20740
Fighting against viral hepatitis: Lessons from Taiwan
Authors: Chen Ding-Shinn
Published: July 2011

Viral hepatitis and its sequelae are important health problems worldwide, including Taiwan. For the last 40 years, Taiwan's scientists and health care providers have worked hard to control these sequelae, and the results have been excellent. The author, Ding-Shinn Chen, had a key role in planning and establishing the control program in Taiwan, and participated in the endeavors from the very beginning. In this perspective, he describes how he became interested in research as a medical student, his encounters with hepatitis B and C, how he and his colleagues started early detection of hepatocellular carcinoma (HCC), how he helped Taiwan's government create and implement the Viral Hepatitis Control Program, and how the effectiveness of the program in the decrease of hepatitis B carriage and HCC was monitored. He also discusses how he pioneered the use of interferon-α plus ribavirin to treat chronic hepatitis C. Hepatitis B viral load as a risk factor for HCC and cirrhosis in hepatitis B surface antigen carriers is reviewed briefly, as is the prevention of sequelae by antiviral therapies. Finally, Dr. Chen discusses unresolved issues that must be addressed and predicts the changes of the patterns of liver disease in Taiwan beyond the mid-21st century, which is in part affected by the fight against viral hepatitis that was initiated in the early 1980s.

Conclusion

: Dr. Chen's perspective illustrates Taiwan's fight against viral hepatitis over the last 40 years. This experience can be shared by other countries in which the disease is equally prevalent. (Hepatology 2011;)
Endogenous histones function as alarmins in sterile inflammatory liver injury through Toll-like receptor 9 in mice
Authors: Huang Hai , Evankovich John , Yan Wei , Nace Gary , Zhang Lemeng , Ross Mark , Liao Xinghua , Billiar Timothy , Xu Jun , Esmon Charles T. , Tsung Allan
Published: July 2011

Sterile inflammatory insults are known to activate innate immunity and propagate organ damage through the recognition of extracellular damage-associated molecular pattern (DAMP) molecules. Although DAMPs such as endogenous DNA and nuclear high-mobility group box 1 have been shown to be critical in sterile inflammation, the role of nuclear histone proteins has not yet been investigated. We report that endogenous histones function as DAMPs after ischemic injury through the pattern recognition receptor Toll-like receptor (TLR) 9 to initiate inflammation. Using an

in vivo

model of hepatic ischemia/reperfusion (I/R) injury, we show that levels of circulating histones are significantly higher after I/R, and that histone neutralization significantly protects against injury. Injection of exogenous histones exacerbates I/R injury through cytotoxic effects mediated by TLR9 and MyD88. In addition, histone administration increases TLR9 activation, whereas neither TLR9 nor MyD88 mutant mice respond to exogenous histones. Furthermore, we demonstrate

in vitro

that extracellular histones enhance DNA-mediated TLR9 activation in immune cells through a direct interaction.

Conclusion:

These novel findings reveal that histones represent a new class of DAMP molecules and serve as a crucial link between initial damage and activation of innate immunity during sterile inflammation. (HEPATOLOGY 2011; 54:999–1008)
Intercellular nanovesicle-mediated microRNA transfer: A mechanism of environmental modulation of hepatocellular cancer cell growth
Authors: Kogure Takayuki , Lin Wen-Lang , Yan Irene K. , Braconi Chiara , Patel Tushar
Published: July 2011

Hepatocellular carcinoma (HCC) is characterized by a propensity for multifocality, growth by local spread, and dysregulation of multiple signaling pathways. These features may be determined by the tumoral microenvironment. The potential of tumor cells to modulate HCC growth and behavior by secreted proteins has been extensively studied. In contrast, the potential for genetic modulation is poorly understood. We investigated the role and involvement of tumor-derived nanovesicles capable of altering gene expression and characterized their ability to modulate cell signaling and biological effects in other cells. We show that HCC cells can produce nanovesicles and exosomes that differ in both RNA and protein content from their cells of origin. These can be taken up and internalized by other cells and can transmit a functional transgene. The microRNA (miRNA) content of these exosomes was examined, and a subset highly enriched within exosomes was identified. A combinatorial approach to identify potential targets identified transforming growth factor β activated kinase-1 (TAK1) as the most likely candidate pathway that could be modulated by these miRNAs. Loss of TAK1 has been implicated in hepatocarcinogenesis and is a biologically plausible target for intercellular modulation. We show that HCC cell-derived exosomes can modulate TAK1 expression and associated signaling and enhance transformed cell growth in recipient cells.

Conclusion

: Exosome-mediated miRNA transfer is an important mechanism of intercellular communication in HCC cells. These observations identify a unique intercellular mechanism that could potentially contribute to local spread, intrahepatic metastases, or multifocal growth in HCC. (Hepatology 2011;)
Spontaneous repopulation of β-catenin null livers with β-catenin-positive hepatocytes after chronic murine liver injury
Authors: Thompson Michael D. , Wickline Emily D. , Bowen William B. , Lu Amy , Singh Sucha , Misse Amalea , Monga Satdarshan P.S.
Published: July 2011

Prolonged exposure of mice to diet containing 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) results in hepatobiliary injury, atypical ductular proliferation, oval cell appearance, and limited fibrosis. Previously, we reported that short-term ingestion of DDC diet by hepatocyte-specific β-catenin conditional knockout (KO) mice led to fewer A6-positive oval cells than wildtype (WT) littermates. To examine the role of β-catenin in chronic hepatic injury and repair, we exposed WT and KO mice to DDC for 80 and 150 days. Paradoxically, long-term DDC exposure led to significantly more A6-positive cells, indicating greater atypical ductular proliferation in KO, which coincided with increased fibrosis and cholestasis. Surprisingly, at 80 and 150 days in KO we observed a significant amelioration of hepatocyte injury. This coincided with extensive repopulation of β-catenin null livers with β-catenin-positive hepatocytes at 150 days, which was preceded by appearance of β-catenin-positive hepatocyte clusters at 80 days and a few β-catenin-positive hepatocytes at earlier times. Intriguingly, occasional β-catenin-positive hepatocytes that were negative for progenitor markers were also observed at baseline in the KO livers, suggesting spontaneous escape from cre-mediated recombination. These cells with hepatocyte morphology expressed mature hepatocyte markers but lacked markers of hepatic progenitors. The gradual repopulation of KO livers with β-catenin-positive hepatocytes occurred only following DDC injury and coincided with a progressive loss of hepatic cre-recombinase expression. A few β-catenin-positive cholangiocytes were observed albeit only after long-term DDC exposure and trailed the appearance of β-catenin-positive hepatocytes.

Conclusion:

In a chronic liver injury model, β-catenin-positive hepatocytes exhibit growth and survival advantages and repopulate KO livers, eventually limiting hepatic injury and dysfunction despite increased fibrosis and intrahepatic cholestasis. (Hepatology 2011;)
The hydrological behaviour of urban streets: long‐term observations and modelling of runoff losses and rainfall–runoff transformation
Authors: Ramier D. , Berthier E. , Andrieu H.
Published: July 2011

Runoff on impervious surfaces (roads, roofs, etc.) raises a number of environmental and road safety‐related problems. The primary objective of this research effort is to improve our knowledge of the hydrological behaviour of impervious urban surfaces in order to better assess runoff on these surfaces and its subsequent consequences. This article will focus on two street stretches studied over a 38‐month period. Measurements of rainfall and runoff discharge on these stretches have made it possible to estimate runoff losses as well as to constitute a database for modelling purposes. On the basis of these data, two models have been used, one simple the other more detailed and physically based. For both models, runoff discharges at a 3‐min time step are well reproduced, although runoff coefficients and runoff losses are still poorly estimated. Detailed analyses of experimental data and model output, however, indicate that runoff losses could be quite high on such ‘impervious surfaces’ (between 30 and 40% of total rainfall, depending on the street stretch) and that these losses are mainly because of evaporation and infiltration inside the road structure. Copyright © 2011 John Wiley & Sons, Ltd.
Breast cancer incidence trends in Norway—explained by hormone therapy or mammographic screening?
Authors: Hofvind Solveig , Sakshaug Solveig , Ursin Giske , Graff‐Iversen Sidsel
Published: July 2011

A decline in breast cancer incidence has been observed in several countries after 2002. Reduced use of menopausal hormonal therapy (HT), as a consequence of the publication of results from the Women's Health Initiative, has been argued to be the main reason. In Norway, the governmentally funded Norwegian Breast Cancer Screening Program (NBCSP) was implemented during the same time period as the increased use of HT. This study investigated trends in breast cancer incidence by use of HT and introduction of the screening program. We obtained rates of breast cancer from the Cancer Registry of Norway and sales data of HT preparations from the Norwegian Institute of Public Health. Mammography rates were estimated from published reports. Breast cancer incidence rates increased steadily from 1956 to the end of the 20th century, particularly in women aged 55–69 during 1996–2002 residing in the counties where the NBCSP was first introduced. The rates declined after 2002–2003. HT use increased in 1987–2001, peaking around year 2000. In particular, sales of combined estrogen and progestogen preparations declined after 2002. Among women aged 55–59, rates of hormone receptor positive breast cancers peaked in 2000–2003. No such trend was seen in other age groups. In conclusion, the interpretation of breast cancer incidence trends in Norway from 1987 to 2009 is complicated because the NBCSP was introduced during a period with increasing HT use. Both factors likely contributed to the observed trends, and the role of each may vary across age groups.
On the simultaneity problem in the aid and growth debate
Authors: Brückner Markus
Published: July 2011

This paper shows that foreign aid has a significant positive average effect on real per capita gross domestic product (GDP) growth if, and only if, the quantitatively large negative reverse causal effect of per capita GDP growth on foreign aid is adjusted for in the growth regression. Instrumental variables estimates show that a 1 percentage point increase in GDP per capita growth decreased foreign aid by over 4%. Adjusting for this quantitatively large, negative reverse causal effect of economic growth on foreign aid shows that a 1% increase in foreign aid increased real per capita GDP growth by around 0.1 percentage points. Copyright © 2011 John Wiley & Sons, Ltd.
Caffeine induction of sulfotransferases in rat liver and intestine
Authors: Zhou Tianyan , Chen Yue , Huang Chaoqun , Chen Guangping
Published: July 2011

Sulfotransferases (SULTs) are important phase II drug‐metabolizing enzymes. Regulation of SULTs by hormones and other endogenous molecules is relatively well understood, while xenobiotic induction of SULTs is not well studied. Caffeine is one of the most widely consumed psychoactive substances. However, SULT regulation by caffeine has not been reported. In this report, male and female rats were treated with different oral doses of caffeine (2, 10, 50 mg kg−1 per day) for 7 days. Western blot and real‐time RT‐PCR were used to investigate the changes in SULT protein and mRNA expression following the caffeine treatment. Caffeine induced both rat aryl sulfotransferase (rSULT1A1, AST‐IV) and rat hydroxysteroid sulfotransferase (rSULT2A1, STa) in the liver and intestine of female rats in a dose‐dependent manner. Caffeine induction of rSULT1A1 and rSULT2A1 in the female rat intestine was much stronger than that in the liver. Although caffeine induced rSULT1A1 significantly in the male rat liver, it did not significantly induce rSULT2A1. In male rat intestine, caffeine significantly induced rSULT2A1. The different SULTs induction patterns in male and female rats suggest that the regulation of rat SULTs by caffeine may be affected by different hormone secretion patterns and levels. Our results suggest that consumption of caffeine can induce drug metabolizing SULTs in drug detoxification tissues. Copyright © 2011 John Wiley & Sons, Ltd.
A novel polymer‐free paclitaxel‐eluting stent with a nanoporous surface for rapid endothelialization and inhibition of intimal hyperplasia: Comparison with a polymer‐based sirolimus‐eluting stent and bare metal stent in a porcine model
Authors: Jia Haibo , Liu Haixia , Kong Junying , Hou Jingbo , Wu Jian , Zhang Maomao , Tian Jinwei , Liu Huimin , Ma Lijia , Hu Sining , Huang Xingtao , Zhang Shaosong , Zhang Shuo , Yu Bo , Jang Ik‐Kyung
Published: July 2011

Hypersensitivity and inflammatory responses to polymers may be responsible for late stent thrombosis after implantation of a drug‐eluting stent (DES). Polymer‐free DES may reduce the prevalence of these adverse reactions in vessels. We evaluated a polymer‐free paclitaxel‐eluting‐stent with a nanoporous surface (nano‐PES) for endothelialization and inhibition of neointimal hyperplasia by optical coherence tomography (OCT) and pathology in a porcine model. Nano‐PES with high‐dose (HD) and low‐dose (LD) paclitaxel (1.0 μg/mm2 and 0.4 μg/mm2, respectively) was compared with a sirolimus‐eluting stent (SES) and bare‐metal stent (BMS) in a porcine model. Fifty‐three stents (14 HD, 14 LD, 14 SES, 11 BMS) were implanted in 18 minipigs. At 14 days, nano‐PES with HD and LD showed more complete endothelialization compared with SES. BMS had 100% endothelial coverage. At 28 days, a significant reduction in neointimal hyperplasia was detected by OCT in the nano‐PES HD group compared with BMS. No benefit in prevention of the neointimal hyperplasia was observed in the nano‐PES LD group. Nano‐PES stents showed decreased deposition of fibrin and inflammation compared with SES. Pharmacokinetic studies revealed that nano‐PES could effectively deliver the drug to the local coronary artery and it released the drug more rapidly than SES. Such a release profile was favorable for rapid endothelialization of nano‐PES. The present study showed the nano‐PES to be a new drug‐delivery technology; that it used a nanoporous stent surface; that it offered desirable drug‐elution properties without the use of polymers; that it may translate into an improved safety profile for next‐generation DES. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Agreement between self‐report and archival public service utilization data among chronically homeless individuals with severe alcohol problems
Authors: Clifasefi Seema L. , Collins Susan E. , Tanzer Kenneth , Burlingham Bonnie , Hoang Sara E. , Larimer Mary E.
Published: July 2011

Public service utilization data are often used as key outcomes in studies on homelessness. Although self‐report data on these outcomes are accessible and cost‐effective, various factors may affect retrospective recall in homeless populations. It is therefore necessary to establish validity of self‐report to ensure the integrity of studies involving such populations. Participants (N=134) were chronically homeless individuals with severe alcohol problems who participated in a housing first effectiveness trial (Larimer et al., 2009). The authors compared 30‐day and 3‐year retrospective self‐report data on sobering center, jail, and hospital use with archival records corresponding to the same timeframes. Analyses indicated good category‐specific agreement for 30‐day self‐report and archival data on sobering center (82%; κ=.58) and jail use (89%; κ=.60). Hospital use, however, was self‐reported significantly more frequently than indicated by archival data (78%; κ=.30). Three‐year data showed inadequate agreement across all three variables. © 2011 Wiley Periodicals, Inc.
Sense of community and interethnic relations: comparing local communities varying in ethnic heterogeneity
Authors: Castellini Federica , Colombo Monica , Maffeis Daniele , Montali Lorenzo
Published: July 2011

This study investigates the sense of community and interethnic relations in two different metropolitan areas that vary in ethnic heterogeneity. The study was conducted in Milan, Italy using a sample of 318 participants living in different city districts that vary in ethnic heterogeneity (low vs. high). The participants completed a questionnaire that assessed their psychological sense of community, blatant and subtle prejudice, host community acculturation strategies, and some measures of contact (quality, quantity, and type). The results indicate that high ethnic heterogeneity is related to a lower sense of community, higher blatant prejudice, and exclusionism. Residents living in lower ethnic heterogeneity neighborhoods reported closer contact opportunities and lower levels of prejudice. © 2011 Wiley Periodicals, Inc.
Zearalenone induces apoptosis and necrosis in porcine granulosa cells via a caspase‐3‐ and caspase‐9‐dependent mitochondrial signaling pathway
Authors: Zhu Li , Yuan Hui , Guo Chengzhi , Lu Yin , Deng Sijun , Yang Yang , Wei Qiang , Wen Lixin , He Zuping
Published: July 2011

Zearalenone is a mycotoxin produced mainly by Fusarium. There are numerous incidences of mycotoxicosis in laboratory and domestic animals, especially in pigs. However, little is known about molecular mechanisms of zearalenone toxicity. Granulosa cells are the maximal cell population in follicles, and they play an essential role in the development and maturation of follicles. The objective of this study was to explore the effect of zearalenone at high concentrations on proliferation and apoptosis of porcine granulosa cells and uncover signaling pathway underlying the cytotoxicity of zearalenone. We found that zearalenone reduced the proliferation of porcine granulosa cells in a dose‐dependent manner as shown by the MTT assay and zearalenone resulted in an obvious apoptosis and necrosis in porcine granulosa cells as determined by the TUNEL analysis and flow cytometry. In addition, TUNEL assay with caspase inhibitors showed that zearalenone triggered a caspase‐3‐ and caspase‐9‐dependent apoptotic process in porcine granulosa cells. Fluorescence spectrophotometer displayed that zearalenone led to a loss of mitochondrial transmembrane potential of porcine granulosa cells but enhanced reactive oxygen species (ROS) levels of the cells. Notably, Western blots revealed that caspase‐3 and caspase‐9 were activated by zearalenone in porcine granulosa cells. Collectively, our results suggest that zearalenone induces apoptosis and necrosis of porcine granulosa cells in a dose‐dependent manner via a caspase‐3‐ and caspase‐9‐dependent mitochondrial pathway. This study thus offers a novel insight into molecular mechanisms by which zearalenone has adverse cytotoxicity on reproduction. J. Cell. Physiol. 227: 1814–1820, 2012. © 2011 Wiley Periodicals, Inc.
Mouse embryonic stem cells that survive γ‐rays exposure maintain pluripotent differentiation potential and genome stability
Authors: Rebuzzini Paola , Pignalosa Diana , Mazzini Giuliano , Di Liberto Riccardo , Coppola Antonio , Terranova Nadia , Magni Paolo , Redi Carlo Alberto , Zuccotti Maurizio , Garagna Silvia
Published: July 2011

This study aimed to investigate the cell cycle, apoptosis, cytogenetics and differentiation capacity of mouse embryonic stem cells (mESCs) that survived a single dose of 2 or 5 Gy γ‐rays during a period of up to 96 h of culture. After 2 Gy irradiation and 24 h culture, compared to control, a significant majority of cells was blocked at the G2/M phase and a massive apoptosis was recorded. Between 48 and 72 h post‐irradiation, the parameters used to describe the cell cycle and apoptosis returned similar to those of control samples. When mESCs were irradiated with 5 Gy, a small fraction of cells, even after 96 h of culture, still presented clear evidences of a G2/M block and apoptosis. The cytogenetic analysis performed at 96 h showed that the structural stability of the aberrations did not change significantly when comparing control and 2 or 5 Gy‐treated populations. However, the chromosomal damage observed in the progeny of the survived cells after 5 Gy exposure is significantly higher than that observed in control samples, although it is mostly of the stable and transmissible type. Ninety‐six hours after irradiation, the survived mESCs maintained their undifferentiated status and capability to differentiate into the three germ layers. Overall, these results indicate a commitment of mESCs to maintain pluripotency and genome stability. J. Cell. Physiol. 227: 1242–1249, 2012. © 2011 Wiley Periodicals, Inc.
Afadin controls p120‐catenin–ZO‐1 interactions leading to endothelial barrier enhancement by oxidized phospholipids
Authors: Birukova Anna A. , Fu Panfeng , Wu Tinghuai , Dubrovskyi Oleksii , Sarich Nicolene , Poroyko Valery , Birukov Konstantin G.
Published: July 2011

Afadin is a novel regulator of epithelial cell junctions assembly. However, its role in the formation of endothelial cell junctions and the regulation of vascular permeability remains obscure. We previously described protective effects of oxidized 1‐palmitoyl‐2‐arachidonoyl‐sn‐glycero‐3‐phosphorylcholine (OxPAPC) in the in vitro and in vivo models of lung endothelial barrier dysfunction and acute lung injury, which were mediated by Rac GTPase. This study examined a role of afadin in the OxPAPC‐induced enhancement of interactions between adherens junctions and tight junctions as a novel mechanism of endothelial cell (EC) barrier preservation. OxPAPC induced Rap1‐dependent afadin accumulation at the cell periphery and Rap1‐dependent afadin interaction with adherens junction and tight junction proteins p120‐catenin and ZO‐1, respectively. Afadin knockdown using siRNA or ectopic expression of afadin mutant lacking Rap1 GTPase binding domain suppressed OxPAPC‐induced EC barrier enhancement and abolished barrier protective effects of OxPAPC against thrombin‐induced EC permeability. Afadin knockdown also abolished protective effects of OxPAPC against ventilator‐induced lung injury in vivo. These results demonstrate for the first time a critical role of afadin in the regulation of vascular barrier function in vitro and in vivo via coordination of adherens junction–tight junction interactions. J. Cell. Physiol. 227: 1883–1890, 2012. © 2011 Wiley Periodicals, Inc.
Hyal‐1 but not hyal‐3 deficiency has an impact on ovarian folliculogenesis and female fertility by altering the follistatin/activin/Smad3 pathway and the apoptotic process
Authors: Dumaresq‐Doiron Karine , Edjekouane Lydia , Orimoto Adriana Mari , Yoffou Paule Héléna , Gushulak Lara , Triggs‐Raine Barbara , Carmona Euridice
Published: July 2011

Ovarian follicle development is a process regulated by various endocrine, paracrine and autocrine factors that act coordinately to promote follicle growth. However, the vast majority of follicles does not reach the pre‐ovulatory stage but instead, undergo atresia by apoptosis. We have recently described a role for the somatic hyaluronidases (Hyal‐1, Hyal‐2, and Hyal‐3) in ovarian follicular atresia and induction of granulosa cell apoptosis. Herein, we show that Hyal‐1 but not Hyal‐3 null mice have decreased apoptotic granulosa cells after the induction of atresia and an increased number of retrieved oocytes after stimulation of ovulation. Furthermore, young Hyal‐1 null mice had a significantly higher number of primordial follicles than age matched wild‐type animals. Recruitment of these follicles at puberty resulted in an increased number of primary and healthy preantral follicles in Hyal‐1 null mice. Consequently, older Hyal‐1 deficient female mice have prolonged fertility. At the molecular level, immature Hyal‐1 null mice have decreased mRNA expression of follistatin and higher levels of phospho‐Smad3 protein, resulting in increased levels of phospho‐Akt in pubertal mice. Hyal‐1 null ovarian follicles did not exhibit hyaluronan accumulation. For Hyal‐3 null mice, compensation by Hyal‐1 or Hyal‐2 might be related to the lack of an ovarian phenotype. In conclusion, our results demonstrate that Hyal‐1 plays a key role in the early phases of folliculogenesis by negatively regulating ovarian follicle growth and survival. Our findings add Hyal‐1 as an ovarian regulator factor for follicle development, showing for the first time an interrelationship between this enzyme and the follistatin/activin/Smad3 pathway. J. Cell. Physiol. 227: 1911–1922, 2012. © 2011 Wiley Periodicals, Inc.
NADPH oxidase 4 mediates upregulation of type 4 phosphodiesterases in human endothelial cells
Authors: Muzaffar Saima , Jeremy Jamie Y. , Angelini Gianni D. , Shukla Nilima
Published: July 2011

The protective actions of prostacyclin (PGI2) are mediated by cyclic AMP (cAMP) which is reduced by type 4 phosphodiesterases (PDE4) which hydrolyze cAMP. Superoxide ${\left( {{\rm O}_{2}^{{-} } } \right)}$ from NADPH oxidase (Nox) is associated with impaired PGI2 bioactivity. The objective of this study, therefore, was to study the relationship between Nox and PDE4 expression in human umbilical vein endothelial cells (HUVECs). HUVECs were incubated with the thromboxane A2 analog, U46619, 8‐isoprostane F2α (8IP), or tumor necrosing factor alpha (TNFα) [±iloprost (a PGI2 analog)] and the expression of PDE4A, B, C, and D and splice variants thereof assessed using Western blotting and qPCR and mRNA silencing of Nox4 and Nox5. Effects on cell replication and angiogenesis were also studied. U46619, 8IP, and TNFα increased the expression of Nox 4 and Nox 5 and all PDE4 isoforms as well as cell replication and tubule formation (index of angiogenesis), effects inhibited by mRNA silencing of Nox4 (but not Nox5) and iloprost and rolipram. These data demonstrate that upregulation of Nox4 leads to an upregulation of PDE4A, B, and D and increased hydrolysis of cAMP which in turn augments cell replication and angiogenesis. This mechanism may be central to vasculopathies associated with endothelial dysfunction since the PGI2–cAMP signaling axis plays a key role in mediating functions that include hemostasis and angiogenesis. J. Cell. Physiol. 227: 1941–1950, 2012. © 2011 Wiley Periodicals, Inc.
Rspo2/Int7 regulates invasiveness and tumorigenic properties of mammary epithelial cells
Authors: Klauzinska Malgorzata , Baljinnyam Bolormaa , Raafat Ahmed , Rodriguez‐Canales Jaime , Strizzi Luigi , Endo Greer Yoshimi , Rubin Jeffrey S. , Callahan Robert
Published: July 2011

Rspo2 was identified as a novel common integration site (CIS) for the mouse mammary tumor virus (MMTV) in viral induced mouse mammary tumors. Here we show that Rspo2 modulates Wnt signaling in mouse mammary epithelial cells. Co‐expression of both genes resulted in an intermediate growth phenotype on plastic and had minor effects on the growth‐promoting properties of Wnt1 in soft agar. However, individual Rspo2 and Wnt1 HC11 transfectants as well as the double transfectant were tumorigenic in athymic nude mice, with tumors from each line having distinctive histological characteristics. Rspo2 and Rspo2/Wnt1 tumors contained many spindle cells, consistent with an epithelial–mesenchymal transformation (EMT) phenotype. When Rspo2 and Rspo2/Wnt1 tumor cells were transferred into naïve mice, they exhibited greater metastatic activity than cells derived from Wnt1 tumors. For comparison, C57MG/Wnt1/Rspo2 co‐transfectants exhibited invasive properties in three‐dimensional (3D) Matrigel cultures that were not seen with cells transfected only with Wnt1 or Rspo2. Use of Dickkopf‐1, a specific antagonist of the Wnt/β‐catenin pathway, or short hairpin RNA targeting β‐catenin expression demonstrated that the invasive activity was not mediated by β‐catenin. Our results indicate that Rspo2 and Wnt1 have mutually distinct effects on mammary epithelial cell growth and these effects are context‐dependent. While Rspo2 and Wnt1 act synergistically in the β‐catenin pathway, other mechanisms are responsible for the invasive properties of stable double transfectants observed in 3D Matrigel cultures. J. Cell. Physiol. 227: 1960–1971, 2012. © 2011 Wiley Periodicals, Inc.
3H‐L‐leucine transport by the promiscuous crustacean dipeptide‐like cotransporter
Authors: Obi I. , Wells A.L. , Ortega P. , Patel D. , Farah L. , Zanotto F.P. , Ahearn G.A.
Published: July 2011

The crustacean intestine and hepatopancreas display a variety of solute transport mechanisms for transmembrane transfer of dietary contents from lumen to epithelial cytosol. An in vitro intestinal perfusion apparatus was used to characterize mucosal to serosoal (MS) and serosal to mucosal (SM) Zn2+‐dependent 3H‐L‐leucine transport by the intestine of the American lobster, Homarus americanus. Transmural 20 µM MS 3H‐L‐leucine fluxes across lobster intestine were a hyperbolic function of luminal zinc concentration (1–50 µM) following Michaelis–Menten kinetics (Km = 2.67 ± 0.74 µM; Jmax = 19.56 ± 2.22 pmol/cm2×min). Transmural 20 µM SM 3H‐L‐leucine fluxes were not affected by serosal zinc, resulting in a highly significant stimulation of net amino acid transfer to the blood by luminal metal. MS fluxes of 20 µM 3H‐L‐leucine were also hyperbolic functions of luminal [Cu2+], [Mn2+], [Na+], and [H+]. MS flux of 3H‐L‐leucine was a sigmoidal function of luminal [L‐leucine] and was stimulated by the addition of 20 µM luminal zinc at both pH 7.0 and 5.5. A greater enhanced amino acid transport occurred at the lower pH 5.5. MS flux of 20 µM 3H‐L‐leucine in the presence of 20 µM zinc was significantly inhibited by addition of 100 µM luminal glycylsarcosine, and MS flux of 20 µM 3H‐glycylsarcosine was inhibited by 100 µM L‐leucine in the presence of 20 µM zinc. Results suggest that 3H‐L‐leucine and metals form a complex (e.g., Leu–Zn–Leu] that may functionally mimic dipeptides and use a dipeptide‐like transporter during MS fluxes as suggested for fish and mammals. J. Exp. Zool. 315:465–475, 2011. © 2011 Wiley‐Liss, Inc.