bluuebunny/crossref_metadata_2025 huggingface dataset:
One‐Step Wet‐Spinning Process of Poly(3,4‐ethylenedioxythiophene):Poly(styrenesulfonate) Fibers and the Origin of Higher Electrical Conductivity
Authors: Jalili Rouhollah , Razal Joselito M. , Innis Peter C. , Wallace Gordon G.
Published: July 2011

A simplified wet‐spinning process for the production of continuous poly (3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) fibers is reported. Conductivity enhancement of PEDOT:PSS fibers up to 223 S cm−1 has been demonstrated when these fibers are exposed to ethylene glycol as a post‐synthesis processing step. In a new spinning approach it is shown that by employing a spinning formulation consisting of an aqueous blend of PEDOT:PSS and poly(ethlylene glycol), the need for post‐spinning treatment with ethylene glycol is eliminated. With this approach, 30‐fold conductivity enhancements from 9 to 264 S cm−1 are achieved with respect to an untreated fiber. This one‐step approach also demonstrates a significant enhancement in the redox properties of the fibers. These improvements are attributed to an improved molecular ordering of the PEDOT chains in the direction of the fiber axis and the consequential enrichment of linear (or expanded‐coil like) conformation to preference bipolaronic electronic structures as evidenced by Raman spectroscopy, solid‐state electron spin resonance (ESR) and in situ electrochemical ESR studies.
Enhanced Transport of Nanoparticles Across a Porous Nanotube Sponge
Authors: Li Hongbian , Gui Xuchun , Zhang Luhui , Ji Chunyan , Zhang Yichi , Sun Pengzhan , Wei Jinquan , Wang Kunlin , Zhu Hongwei , Wu Dehai , Cao Anyuan
Published: July 2011

The movement of nanoparticles across cell membranes in a controlled manner is important for developing applications related to filtration, penetration, and biological systems. Here, the tunable transport of metal nanoparticle suspensions with well‐defined particle sizes and surface groups through a ≈1 mm‐thick porous carbon nanotube sponge filter is reported. Au particles with a relatively large diameter (40 nm) alone are easily trapped by the nanotube sponge even in a dilute water flow, but they can quickly pass through the sponges by the addition of much smaller particles (4 nm) to the suspension. A mechanistic study shows that the dominating interaction mode between Au particles and the sponge is physical trapping within the nanotube networks rather than Coulomb attraction. In the nanoparticle mixture, surface groups on the small particles tend to form hydrogen bonds with groups on large particles, thereby increasing interparticle distances, and preventing formation of severe agglomerates; large particles can therefore move across interconnected nanotubes more smoothly. It might be possible to switch the transport of many different nanoparticles across porous media on and off by adding or removing smaller particles of the same type.
Insights into the pathogenesis of systemic sclerosis based on the gene expression profile of progenitor‐derived endothelial cells
Authors: Avouac Jérôme , Cagnard Nicolas , Distler Jörg H. , Schoindre Yoland , Ruiz Barbara , Couraud Pierre Olivier , Uzan Georges , Boileau Catherine , Chiocchia Gilles , Allanore Yannick
Published: July 2011

Objective

To determine the gene expression profile of endothelial cells derived from the endothelial progenitor cells (EPCs) of patients with systemic sclerosis (SSc).

Methods

Microarray experiments were performed on Affymetrix GeneChip Human Exon 1.0 ST Arrays in unstimulated and hypoxia‐stimulated EPC‐derived cells from patients with SSc and control subjects. Followup of the raised hypotheses was performed ex vivo by immunohistochemical analysis of skin tissue.

Results

Signals from 92 probe sets and 188 probe sets were different in unstimulated and hypoxia‐stimulated cells, respectively, from patients with SSc compared with controls. Within the largest groups of genes related to cell–cell interaction and vascular remodeling, down‐regulation of tumor necrosis factor ligand superfamily member 10 (TNFSF10) and homeobox A9 (HOX‐A9) was confirmed by real‐time polymerase chain reaction and Western blots in EPC‐derived cells and by immunohistochemistry in SSc skin tissue. Signals from 221 and 307 probe sets were different in unstimulated and hypoxia‐stimulated cells, respectively, from patients with diffuse cutaneous SSc compared with patients with limited cutaneous SSc. Within the largest group of genes related to the inflammatory response, differential expression of TNFα‐induced protein 3 and prostaglandin‐endoperoxide synthase 2 was observed in EPC‐derived cells and skin tissue from patients with SSc.

Conclusion

Our data revealed important gene expression changes in EPC‐derived endothelial cells from patients with SSc, characterized by a proadhesive, proinflammatory, and activated phenotype. Differential expression in lesional SSc skin tissue of new targets, such as TNF family members and HOX‐A9, may contribute to the pathogenesis of SSc and deserves more in‐depth exploration.
Anatomical Sciences Education Vol. 4, Issue 4, 2011 Cover Image
Authors: McBride Jennifer M. , Drake Richard L.
Published: July 2011

Medical students at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University receive instruction from a resident at the cadaver during their anatomy course. As discussed by McBride and Drake in this issue of ASE, residents teaching in the anatomy course at his institution who satisfy specific requirements qualify for an academic appointment as a Clinical Instructor.
Assessment of female reproductive endpoints in Sprague–Dawley rats developmentally exposed to Diuron: potential ovary toxicity
Authors: Grassi Tony Fernando , Guerra Marina Trevisan , Perobelli Juliana Elaine , de Toledo Fabíola Choqueta , da Silva Denise Salioni , De Grava Kempinas Wilma , Barbisan Luís Fernando
Published: July 2011

BACKGROUND: Diuron is widely used in agriculture but its deleterious effects on the reproductive system and mammary gland are still poorly understood. This study evaluated whether early‐life‐stage exposure to Diuron alters puberty onset or susceptibility to mammary carcinogenesis in female Sprague–Dawley rats. METHODS AND RESULTS: Pregnant rats received basal diet or diet containing Diuron at 500, 750, and 1,250 ppm, from gestational day 12 to the end of lactation (postnatal day 21 [PND21]). After weaning, female offspring continued receiving basal diet or diet containing Diuron until PND 51. At PND 51, female Sprague–Dawley offspring received a single dose of 50 mg/kg b.w. of 7,12‐dimethylbenz(a)anthracene (DMBA) for initiation of mammary carcinogenesis. The animals were sacrificed on PND 51, 75, and 226 to 233 (week 25) for mammary gland morphology, reproductive organs and tumor analysis, respectively. There were no significant differences among groups on vaginal opening, estrous cycle, mammary morphology, or carcinogenesis. However, reductions in ovary weight and corpora lutea were observed at PND 75 in the group treated with Diuron at 1,250 ppm. CONCLUSIONS: The findings suggesting that Diuron exposure (1,250 ppm) may have been potentially toxic to the ovaries. Birth Defects Res (Part B) 92:478–496, 2011. © 2011 Wiley Periodicals, Inc.
USING CONDITIONAL DISCRIMINATION PROCEDURES TO STUDY REMEMBERING IN AN ALZHEIMER'S PATIENT
Authors: Steingrimsdottir Hanna Steinunn , Arntzen Erik
Published: July 2011

Dementia is characterized by memory impairment, but it has been suggested that conditional discrimination procedures can be used to study remembering behavior. The paper presents an experiment in which conditional discrimination procedures were used with a patient diagnosed with Alzheimer's disease. The purpose of the study was two‐fold: (i) compare performance during arbitrary and identity matching‐to sample (MTS) tasks and (ii) study the effect of different delays on the participant's responding. The results show that the participant did not respond correctly on the arbitrary MTS tasks but respond correctly on the simultaneous identity MTS tasks. Thus, the participant responded correctly on identity MTS tasks with a 0‐s delay and also with 3‐, 6‐, and 9‐s delays; the number of incorrect responses increased with the increasing delay duration. Furthermore, the results also indicate that it is possible to use the delayed matching‐to‐sample procedure to evaluate the effect of medication given to Alzheimer's patients. Copyright © 2011 John Wiley & Sons, Ltd.
A STIMULUS CONTROL PROCEDURE TO DECREASE MOTOR AND VOCAL STEREOTYPY
Authors: O'Connor Alison S. , Prieto Jessica , Hoffmann Barbara , DeQuinzio Jaime A. , Taylor Bridget A.
Published: July 2011

A changing criterion design was used to examine the effects of two stimuli (a green card and a red card), conditioned via discrimination training, on reducing motor and vocal stereotypy in a youngster with autism while he looked at books. During discrimination training, motor and vocal stereotypy was not interrupted in the presence of a green stimulus, but was interrupted in the presence of a red stimulus using manual guidance and appropriate behavior was reinforced. After the participant demonstrated successful discrimination of the stimuli (i.e., the absence of stereotypy in the presence of a red stimulus and the engagement in stereotypy in the presence of a green stimulus), intervention began. During intervention, upon meeting criterion for latency to engage in motor and vocal stereotypy in the presence of the red stimulus for a target duration, the participant was provided access to the green stimulus, which signaled that motor and vocal stereotypy would not be interrupted. The criterion latency to engage in stereotypy in the presence of the red stimulus was systematically increased. Simultaneously, the duration of access to the green stimulus was systematically decreased. The red and green stimuli were faded from poster boards to colored 10 × 10 cm cards, and stimulus control was generalized to the participant's classroom and to a community setting (i.e., public library). Results are discussed in terms of discrimination training as a useful intervention for reducing motor and vocal stereotypy. Copyright © 2011 John Wiley & Sons, Ltd.
Real‐time measurements of human chondrocyte heat production during in vitro proliferation
Authors: Santoro R. , Braissant O. , Müller B. , Wirz D. , Daniels A.U. , Martin I. , Wendt D.
Published: July 2011

Isothermal microcalorimeters (IMC) are highly sensitive instruments that allow the measurement of heat flow in the microwatt range. Due to their detection of minute thermal heat, IMC techniques have been used in numerous biological applications, including the study of fermentation processes, pharmaceutical development, and cell metabolism. In this work, with the ultimate goal of establishing a rapid and real‐time method to predict the proliferative capacity of human articular chondrocytes (HAC), we explored to use of IMC to characterize one of the crucial steps within the process of cartilage tissue engineering, namely the in vitro expansion of HAC. We first established an IMC‐based model for the real‐time monitoring of heat flow generated by HAC during proliferation. Profiles of the heat and heat flow curves obtained were consistent with those previously shown for other cell types. The average heat flow per HAC was determined to be 22.0 ± 5.3 pW. We next demonstrated that HAC proliferation within the IMC‐based model was similar to proliferation under standard culture conditions, verifying its relevance for simulating the typical cell culture application. HAC growth and HAC heat over time appeared correlated for cells derived from particular donors. However, based on the results from 12 independent donors, no predictive correlation could be established between the growth rate and the heat increase rate of HAC. This was likely due to variability in the biological function of HAC derived from different donors, combined with the complexity of tightly couple metabolic processes beyond proliferation. In conclusion, IMC appears to be a promising technique to characterize cell proliferation. However, studies with more reproducible cell sources (e.g., cell lines) could be used before adding the complexity associated with primary human cells. Biotechnol. Bioeng. 2011;108: 3019–3024. © 2011 Wiley Periodicals, Inc.
Bioactive Xenicane Diterpenoids from the Taiwanese Soft Coral Asterospicularia laurae
Authors: Lin Yun‐Sheng , Eid Fazary Ahmed , Chen Chung‐Hsiung , Kuo Yao‐Haur , Shen Ya‐Ching
Published: July 2011

Chemical investigation of the Taiwanese soft coral Asterospicularia laurae has led to the isolation of three new xenicane diterpenoids, named asterolaurins K–M (1–3, resp.). Their chemical structures were determined through extensive spectroscopic analyses (1H‐ and 13C‐NMR, 1H,1H‐COSY, HMBC, and NOESY). Compound 2 exhibited cytotoxic activity against HEp‐2, Daoy, MCF‐7, and WiDr tumor cells.
Oxidative DNA Damage Induced by a Copper(II)1,10‐PhenanthrolineL‐Serine Complex in the Presence of Rutin
Authors: Wang Yong , Dai Panpan , Chen Fu , Yang Zhousheng
Published: July 2011

The capacity of the ternary complex copper(II)1,10‐phenanthrolineL‐serine ([CuPhenSer]) to induce double‐strand scission of DNA was explored by agarose‐gel electrophoresis. It was found that the complex exhibited remarkable activity to damage DNA in the presence of rutin. Analysis of the UV and fluorescence spectra clearly demonstrated that the complex was bound to DNA by intercalation. Further, the occurrence of 8‐hydroxydeoxyguanosine (8‐OHdG), a biomarker of oxidative DNA damage, after the treatment of DNA by the complex in presence of rutin was evidenced by an electrochemical method. Finally, the mechanism of oxidative damage to double‐stranded DNA by the [CuPhenSer] complex in the presence of rutin was discussed.
Computational studies on the conformations of some large‐ring cyclodextrins (CDn, n = 20, 21, 22, 23)
Authors: Ivanov Petko M.
Published: July 2011

Computational studies were carried out on the conformations of large‐ring cyclodextrins with degree of polymerization from 20 to 23. Principal component analysis (PCA) was applied for postprocessing of trajectories from conformational search, based on 100.0 ns molecular dynamics simulations. The dominant PCA modes for concerted motions of the macroring atoms were monitored in a lower‐dimensions subspace. The first six lowest indexed principal components contribute more than 90% of the total atomic motions in all cases, with about 70% (CD21) to 83% (CD22) contribution coming from the three highest‐eigenvalue principal components. Representative average geometries of the cyclodextrin macrorings were also obtained for the whole simulation and for the ten 10.0 ns time intervals of the simulation. We concluded that resemblance exists of the representative conformations of these four cyclodextrins with the circularized three‐turn single helical structure proposed for CD21 from small‐angle X‐ray scattering, as well as with the representative conformations of CD26. Chirality, 2011. © 2011 Wiley‐Liss, Inc.
Current status observation of a three‐state counting process with application to simultaneous accurate and diluted HIV test data
Authors: McKeown Karen , Jewell Nicholas P.
Published: July 2011

The authors examine multistate current status data defined by two survival times of interest where one only observes whether or not each of the individual survival times exceed a common observed monitoring time. An individual can therefore belong to one of three states. The authors are interested in whether current status information on the second event can be used to improve estimation of the distribution function of time to the first event. For both single and multiple monitoring time scenarios, in the fully nonparametric setting, one cannot improve the naïve estimator, using information on the first event only, when estimating “smooth” functionals of the distribution of time to the first event (van der Laan & Jewell, 2003). Therefore, improving the naïve estimator is examined when parametric assumptions about the waiting time between the two events are made. For situations where this waiting time is modifiable by design, the issue of determining the optimal length of the waiting time for estimation of the cumulative hazard of the distribution of time to the first event in the recent past is also addressed. The ideas are motivated by and applied to an example on simultaneous accurate and diluted assay HIV test data. The Canadian Journal of Statistics 39: 475–487; 2011 © 2011 Statistical Society of Canada
Competition by inhibitory oligonucleotides prevents binding of CpG to C‐terminal TLR9
Authors: Avalos Ana M. , Ploegh Hidde L.
Published: July 2011

TLR9 recognizes unmethylated CpG‐containing DNA commonly found in bacteria. Synthetic oligonucleotides containing CpG‐motifs (CpG ODNs) recapitulate the activation of TLR9 by microbial DNA, whereas inversion of the CG dinucleotide within the CpG motif to GC (GpC ODNs) renders such ODNs inactive. This difference cannot be attributed to binding of ODNs to the full‐length TLR9 ectodomain, as both CpG and GpC ODNs bind comparably. Activation of murine TLR9 requires cleavage into an active C‐terminal fragment, which binds CpG robustly. We therefore compared the ability of CpG and GpC ODNs to bind to full‐length and C‐terminal TLR9, and their impact on the cleavage of TLR9. We found that CpG binds better to C‐terminal TLR9 when compared with GpC, despite comparably low binding of both ODNs to full‐length TLR9. Neither CpG nor GpC ODNs affected TLR9 cleavage in murine RAW 264.7 cells stably expressing TLR9‐Myc. Inhibitory ODNs (IN‐ODNs) block TLR9 signaling, but how they do so remains unclear. We show here that inhibitory ODNs do not impede TLR9 cleavage but bind to C‐terminal TLR9 preferentially, and thereby compete for CpG ODN binding both in RAW cells and in TLR9‐deficient cells transduced with TLR9‐Myc. Ligand binding to C‐terminal fragment thus determines the outcome of activation through TLR9.
Lanthanide Carbonates
Authors: Janicki Rafał , Starynowicz Przemysław , Mondry Anna
Published: July 2011

The crystal and molecular structures of the rare earth carbonates with the general formulae [C(NH2)]3[Ln(CO3)4(H2O)]·2H2O (where Ln = Pr3+, Nd3+, Sm3+, Eu3+, Gd3+, Tb3+) and [C(NH2)]3[Ln(CO3)4]·2H2O (where Ln = Y3+, Dy3+, Ho3+, Er3+, Tm3+, Yb3+, Lu3+) were determined. The crystals consist of monomeric [Ln(CO3)4(H2O)]5–or [Ln(CO3)4]5–complex anions in which the carbonate ligands coordinate to the Ln3+ion in a bidentate manner. The spectroscopic (UV/Vis/NIR and IR) properties of the crystalline lanthanide carbonates, as well as their aqueous solutions, were determined. Correlation between the spectroscopic and the structural data enabled us to conclude that the [Ln(CO3)4(OH)]6–and [Ln(CO3)4]5–species predominate in the light and heavy lanthanide solutions, respectively. The nature of the Ln–O interaction was also discussed. The experimental data, as well as the theoretical calculations, indicated that the Ln–O(CO32–) bond is more covalent than the Ln–O(OH2) bond. Moreover, the covalency degree is larger for the heavy lanthanide ions. Inspection of the NBO results revealed that the oxygen hybrids, with the approximate composition sp4, form strongly polarized bonds with the 6s6p5d4hybrids of lutetium.
From Discrete Molecule to One‐Dimension Chain: Two New Nitronyl Nitroxide–Lanthanide Complexes Exhibiting Slow Magnetic Relaxation
Authors: Wang Xiaoling , Bao Xia , Xu Panpan , Li Li
Published: July 2011

A mononuclear lanthanide–radical complex [Tb(hfac)3(NITPhSCH3)2] (1) and a one‐dimensional chain complex [Tb(hfac)3(NITPhSCH3)]n (2) {hfac = hexafluoroacetylacetonate, NITPhSCH3 = 2‐[4‐(methylthio)phenyl]‐4,4,5,5‐tetramethylimidazolin‐1‐oxyl 3‐oxide} have been synthesized. Single‐crystal X‐ray diffraction studies revealed that compound 1 is a mononuclear complex in which two NITPhSCH3 radicals are coordinated as monodentate ligands to the TbIII ion through their NO groups to form a tri‐spin complex, and complex 2 is a 1D chain structure constructed of Tb(hfac)3 units bridged by NITPhSCH3 radicals through their NO groups. The temperature dependence of the magnetic susceptibilities of 1 and 2 indicates ferromagnetic coupling between the TbIII ion and the NITPhSCH3 radical. Frequency‐dependent out‐of‐phase signals of alternating current magnetic susceptibilities were observed at low temperature for both complexes, indicative of slow magnetic relaxation.
Phosphane‐Free Copper‐Catalyzed Decarboxylative Coupling of Alkynyl Carboxylic Acids with Aryl Halides under Aerobic Conditions
Authors: Pan Delin , Zhang Chun , Ding Shengtao , Jiao Ning
Published: July 2011

A phosphane‐free copper‐catalyzed decarboxylative cross‐coupling reaction of alkynyl carboxylic acids with aryl halides was developed. CuBr (1–5 mol‐%) was used as a catalyst in the presence of a β‐diketone ligand in air. The reactions of aryl iodides were conducted in the absence of a Pd catalyst. The ligand plays a key role in this kind of copper catalysis. NaNO2 was disclosed to efficiently improve this kind of decarboxylative cross‐coupling when a nitro group was not present in the substrates.
Sequential injection setup for capillary isoelectric focusing combined with MS detection
Authors: Páger Csilla , Dörnyei Ágnes , Kilár Ferenc
Published: July 2011

Capillary isoelectric focusing in the presence of electroosmosis with sequential injection of carrier ampholytes and sample was found to be suitable for MS detection. The separate injection of the sample and the ampholytes provides good condition to suppress and overcome the undesirable effect of the presence of ampholytes in MS. By the appropriate selection of ampholyte solutions, whose pH range not necessarily covers the pI values of the analytes, the migration of the components can be controlled, and the impact of the ampholytes on MS detection is decreased. The unique applicability of this setup is shown by testing several parameters, such as the application of volatile electrolyte solutions, the type of the ampholytes, the order and the number of the ampholyte and sample zones. Broad and narrow pH range ampholytes were applied in experiments using uncoated capillaries with different lengths for the analyses of substituted nitrophenol dyes to achieve optimal conditions for the MS detection. Although the sample components are not leaving the pH gradient, due to the decrease in the ampholyte concentration at the position of the components, and because the sample components migrate in charged state, the ionisation is more effective for MS detection.
An in‐line SPE strategy to enhance sensitivity in CE for the determination of pharmaceutical compounds in river water samples
Authors: Maijó Irene , Borrull Francesc , Calull Marta , Aguilar Carme
Published: July 2011

In this study, the suitability of solid‐phase extraction (SPE) coupled in‐line to CE with UV–Vis detection was evaluated for the preconcentration and separation of diluted solutions of five pharmaceuticals compounds: benzafibrate, piroxicam, diclofenac sodium, naproxen and clofibric acid. An SPE analyte concentrator containing Oasis® HLB sorbent was constructed without frits and placed near the inlet end of the separation capillary. Different parameters such as sample pH, composition and volume of the elution plug and sample loading time were studied in order to obtain the maximum preconcentration factors. The LODs reached for standard samples were in the range 0.06–0.5 ng/mL with good reproducibility, and the developed strategy provides sensitivity enhancement factors around 14 000‐fold in peak area and 5900‐fold in peak height compared with the normal hydrodynamic injection. Finally, river water samples fortified with the pharmaceutical compounds were analyzed by the developed in‐line SPE‐CE‐UV method in order to show the potential of the methodology for the analysis of environmental aquatic samples. For these samples, high values of relative recoveries, between 73–107% and 79–103% for two concentration levels, 5 and 25 ng/mL, respectively, were obtained and LODs ranged between 0.19 and 1 ng/mL.
Rapid CE‐UV binding tests of environmentally hazardous compounds with polymer‐modified magnetic nanoparticles
Authors: Iqbal Zafar , Alsudir Samar , Miah Musharraf , Lai Edward P. C.
Published: July 2011

Hazardous compounds and bacteria in water have an adverse impact on human health and environmental ecology. Polydopamine (or polypyrrole)‐coated magnetic nanoparticles and polymethacrylic acid‐co‐ethylene glycol dimethacrylate submicron particles were investigated for their fast binding kinetics with bisphenol A, proflavine, naphthalene acetic acid, and Escherichia coli. A new method was developed for the rapid determination of % binding by sequential injection of particles first and compounds (or E. coli) next into a fused‐silica capillary for overlap binding during electrophoretic migration. Only nanolitre volumes of compounds and particles were sufficient to complete a rapid binding test. After heterogeneous binding, separation of the compounds from the particles was afforded by capillary electrophoresis. % binding was influenced by applied voltage but not current flow. In‐capillary coating of particles affected the % binding of compounds.
Advances in the measurement of protein mobility using laser Doppler electrophoresis – the diffusion barrier technique
Authors: Corbett Jason C. W. , Connah Malcolm T. , Mattison Kevin
Published: July 2011

A new technique for the measurement of protein mobility using laser Doppler electrophoresis (LDE) is introduced and characterised. The diffusion barrier approach loads a tiny protein sample volume into a much larger volume of dispersant, which contains the electrodes; the LDE measurement is then recorded before the sample can diffuse to the electrodes. We demonstrate that sample volumes are reduced by up to two orders of magnitude to volumes typically associated with separation techniques (∼50 μL), no reduction in measurement sensitivity occurs, samples can be retrieved usefully intact, post‐measurement and typical measurement times are of the order of minutes. Measurements of BSA mobility up to 75°C and 1 M buffer concentration and lysozyme at a concentration as low as 0.5 mg/mL are demonstrated using the technique with good agreement with literature values.
Quantitative evaluation of lectin‐reactive glycoforms of α1‐acid glycoprotein using lectin affinity capillary electrophoresis with fluorescence detection
Authors: Shimura Kiyohito , Tamura Mayumi , Toda Tosifusa , Yazawa Shin , Kasai Ken‐ichi
Published: July 2011

α1‐Acid glycoprotein (AGP) was previously shown to be a marker candidate of disease progression and prognosis of patients with malignancies by analysis of its glycoforms via lectins. Herein, affinity capillary electrophoresis of fluorescein‐labeled AGP using lectins with the aid of laser‐induced fluorescence detection was developed for quantitative evaluation of the fractional ratios of concanavalin A‐reactive or Aleuria aurantia lectin‐reactive AGP. Labeled AGP was applied at the anodic end of a fused‐silica capillary (50 μm id, 360 μm od, 27 cm long) coated with linear polyacryloyl‐β‐alanyl‐β‐alanine, and electrophoresis was carried out for about 10 min in 60 mM 3‐morpholinopropane‐1‐sulfonic acid‐NaOH buffer (pH 7.35). Addition of the lectins to the anode buffer resulted in the separation of lectin‐reactive glycoform peaks from lectin‐non‐reactive glycoform peaks. Quantification of the peak area of each group revealed that the percent of lectin‐reactive AGP is independent of a labeling ratio ranging from 0.4 to 1.5 mol fluorescein/mol AGP, i.e. the standard deviation of 0.5% for an average of 59.9% (n=3). In combination with a facile procedure for micro‐purification of AGP from serum, the present procedure, marking the reactivity of AGP with lectins, should be useful in determining the prognosis for a large number of patients with malignancies.
Determination of eight illegal drugs in human urine by combination of magnetic solid‐phase extraction with capillary zone electrophoresis
Authors: Chen Ming‐Luan , Suo Li‐Li , Gao Qiang , Feng Yu‐Qi
Published: July 2011

Using magnetite/silica/poly(methacrylic acid‐co‐ethylene glycol dimethacrylate) (Fe3O4/SiO2/poly(MAA‐co‐EDMA)) magnetic microspheres, a rapid and high‐throughput magnetic solid‐phase extraction coupled with capillary zone electrophoresis (MSPE‐CZE) method was developed for the determination of illegal drugs (ketamine, amphetamines, opiates, and metabolites). The MSPE of target analytes could be completed within 2 min, and the eight target analytes could be baseline separated within 15 min by CZE with 30 mM phosphate buffer solution (PBS, pH 2.0) containing 15% v/v ACN as background electrolyte. Furthermore, hydrodynamic injection with field‐amplified sample stacking (FASS) was employed to enhance the sensitivity of this MSPE‐CZE method. Under such optimal conditions, the limits of detection for the eight target analytes ranged from 0.015 to 0.105 μg/mL. The application feasibility of MSPE‐CZE in illegal drugs monitoring was demonstrated by analyzing urine samples, and the recoveries of target drugs for the spiked sample ranging from 85.4 to 110.1%. The method reproducibility was tested by evaluating the intra‐ and interday precisions, and relative standard deviations of <10.3 and 12.4%, respectively, were obtained. To increase throughput of the analysis, a home‐made MSPE array that has potential application to the treatment of 96 samples simultaneously was used.
Elevated NRD1 metalloprotease expression plays a role in breast cancer growth and proliferation
Authors: Choong Lee‐Yee , Lim Shen‐Kiat , Chen Yunhao , Loh Marie‐Chiew‐Shia , Toy Weiyi , Wong Chow‐Yin , Salto‐Tellez Manuel , Shah Nilesh , Lim Yoon‐Pin
Published: July 2011

Understanding the molecular etiology of cancer and increasing the number of drugs and their targets are critical to cancer management. In our attempt to unravel novel breast‐cancer associated proteins, we previously conducted protein expression profiling of the MCF10AT model, which comprises a series of isogenic cell lines that mimic different stages of breast cancer progression. NRD1 expression was found to increase during breast cancer progression. Here, we attempted to confirm the relevance of NRD1 in clinical breast cancer and understand the functional role and mechanism of NRD1 in breast cancer cells. Immunohistochemistry data show that NRD1 expression was elevated in ductal carcinoma in situ and invasive ductal carcinomas compared with normal tissues in 30% of the 26 matched cases studied. Examination of NRD1 expression in tissue microarray comprising >100 carcinomas and subsequent correlation with clinical data revealed that NRD1 expression was significantly associated with tumor size, grade, and nodal status (P < 0.05). Silencing of NRD1 reduced MCF10CA1h and MDA‐MD‐231 breast‐cancer‐cell proliferation and growth. Probing the oncogenic EGF signaling pathways revealed that NRD1 knock down did not affect overall downstream tyrosine phosphorylation cascades including AKT and MAPK activation. Instead, silencing of NRD1 resulted in a reduction of overall cyclin D1 expression, a reduction of EGF‐induced increase in cyclin D1 expression and an increase in apoptotic cell population compared with control cells. © 2011 Wiley‐Liss, Inc.
THE EFFECTS OF HIV MEDICATIONS ON THE QUALITY OF LIFE OF OLDER ADULTS IN NEW YORK CITY
Authors: Brent Robert J.
Published: July 2011

A three‐equation model is used to estimate the multiple effects of antiretroviral medications (ARVs) on the quality of life (QoL) of the elderly with HIV in New York City. The transmission mechanism involves the ARVs having a direct effect on QoL via the side effects of the medications and two other effects (one indirect and one reverse) both working through feelings of depression. On a scale of 0 to 100, ARVs raise the QoL by 1 percentage point. This was because there was a large positive indirect effect of ARVs on QoL of 28 percentage points via the reduction in depression, which offsets both the 24 percentage‐point reduction due to the direct effect and the 3 percentage‐point decline from the reverse effect. Now, QoL effects can be applied to the additional life years generated by ARVs to form the quality adjusted life years outcome measure for use in economic evaluations of ARVs. Copyright © 2011 John Wiley & Sons, Ltd.
Five New Biflavonoids from Daphne aurantiaca
Authors: Liang Shuang , Shen Yun‐Heng , Tian Jun‐Mian , Feng Yi , Xiong Zhi , Zhang Wei‐Dong
Published: July 2011

Five new biflavonoids, 1–5, were isolated from the stem bark of Daphne aurantiaca. The structures were elucidated as 2,2″‐bisteppogenin (1), 2,2″‐bisteppogenin 7‐O‐β‐glucopyranoside (2), 2′′′‐dehydroxy‐2,2″‐bisteppogenin (3), 2′′′‐dehydroxy‐2,2″‐bisteppogenin 7‐O‐β‐glucopyranoside (4), and 7‐methoxyneochamaejasmin B (5) on the basis of spectral analyses.
Stereoselective Total Synthesis of Rugulactone
Authors: Das Biswanath , Srinivas Yallamalla , Sudhakar Chithaluri , Raghavendar Reddy Parigi
Published: July 2011

The stereoselective synthesis of the naturally occurring dihydropyranone rugulactone has been accomplished starting from 3‐phenylpropan‐1‐ol employing Maruoka allylation and ring‐closing metathesis as the key steps.
Asymmetric Total Synthesis of Stagonolide G
Authors: Ramesh Dasari , Rajaram Singanaboina , Prabhakar Peddikotla , Ramulu Udugu , Kumar Reddy Dorigondla , Venkateswarlu Yenamandra
Published: July 2011

A simple asymmetric total synthesis of stagonolide G (1) is described. Asymmetric dihydroxylation, regioselective epoxide ring opening, and vinyl Grignard reactions are involved in generating the stereogenic centers C(4) and C(8), followed by Grubbs‐II‐catalyzed ring‐closing metathesis (RCM).
Three New Steroidal Glycosides from the Roots of Cynanchum auriculatum
Authors: Lu Yu , Xiong Hui , Li Teng Hong , Zhong Yang Guang , Nan Mei Zhi
Published: July 2011

Three new C21 steroidal glycosides with a cinnamoyl group at C(12) and a 2‐methylbutanoyl group at C(20), and a straight sugar chain at C(3), namely cyanoauriculosides C–E (1–3, resp.), together with three known steroidal derivatives, were isolated from the roots of Cynanchum auriculatum (Asclepiadaceae). Their structures were determined by spectroscopic analyses and chemical methods. The known constituents were identified as wilfoside K1N (4), cynanauriculoside II (5), and auriculoside IV (6).
Synthesis of 2‐Oxopyridine‐Fused 1,3‐Diazaheterocyclic Compounds via a Three‐Component Reaction
Authors: Alizadeh Abdolali , Mikaeili Azadeh , Firuzyar Tahereh , Ahmadi Mahdi
Published: July 2011

An efficient and simple route for the preparation of 2‐oxopyridine‐fused 1,3‐diazaheterocyclic compounds via a three component reaction is described. It involves the reaction between alkylenediamines 1, 1,1‐bis(methylsulfanyl)‐2‐nitroethene, and alkyl prop‐2‐ynoates 2 in refluxing THF (Table). The structures were corroborated by spectroscopic (IR, 1H‐ and 13C‐NMR, and EI‐MS) and elemental analyses. A plausible mechanism for this type of cyclization is proposed (Scheme).
Suppression by heat shock protein 20 of hepatocellular carcinoma cell proliferation via inhibition of the mitogen‐activated protein kinases and AKT pathways
Authors: Matsushima‐Nishiwaki Rie , Adachi Seiji , Yoshioka Takashi , Yasuda Eisuke , Yamagishi Yasumasa , Matsuura Junya , Muko Masato , Iwamura Rutsu , Noda Takahiro , Toyoda Hidenori , Kaneoka Yuji , Okano Yukio , Kumada Takashi , Kozawa Osamu
Published: July 2011

Heat shock protein (HSP) 20, one of the low‐molecular weight HSPs, is known to have versatile functions, such as vasorelaxation. However, its precise role in cancer proliferation remains to be elucidated. While HSP20 is constitutively expressed in various tissues including the liver, we have previously reported that HSP20 protein levels in human hepatocellular carcinoma (HCC) cells inversely correlate with the progression of HCC. In this study, we investigated the role of HSP20 in HCC proliferation. The activities of extracellular signal‐regulated kinase (ERK), c‐jun N‐terminal kinase (JNK), and AKT were negatively correlated with the HSP20 protein levels in human HCC tissues. Since HSP20 proteins were hardly detected in HCC‐derived cell lines, the effects of HSP20 expression were evaluated using human HCC‐derived HuH7 cells that were stably transfected with wild‐type human HSP20 (HSP20 overexpressing cells). In HSP20 overexpressing cells, cell proliferation was retarded, and the activation of the mitogen‐activated protein kinases (MAPKs) signaling pathways, including the ERK and JNK, and AKT pathways, as well as cyclin D1 accumulation induced by either transforming growth factor‐α (TGFα) or hepatocyte growth factor, were significantly suppressed compared with the empty vector‐transfected cells (control cells). Taken together, our findings strongly suggest that HSP20 suppresses the growth of HCC cells via the MAPKs and AKT signaling pathways, thus suggesting that the HSP20 could be a new therapeutic target for HCC. J. Cell. Biochem. 112: 3430–3439, 2011. © 2011 Wiley Periodicals, Inc.
FLRT2 promotes cellular proliferation and inhibits cell adhesion during chondrogenesis
Authors: Xu Y. , Wei K. , Kulyk W. , Gong S.‐G.
Published: July 2011

One of the earliest events during chondrogenesis is the formation of condensations, a necessary pre‐requisite for subsequent differentiation of a chondrogenic phenotype. Members of the Fibronectin Lecucine Rich Transmembrane (FLRT) proteins have been shown to be involved in cell sorting and neurite outgrowth. Additionally, FLRT2 is highly expressed at putative sites of chondrogenic differentiation during craniofacial development. In this study, we demonstrate that FLRT2 plays a role in mediating cell proliferation and cell–cell interactions during early chondrogenesis. Clones of stable transfectants of a murine chondroprogenitor cell line, ATDC5, were established in which FLRT2 was knocked down or overexpressed. Cells in which FLRT2 was knocked down proliferated at a slower rate compared to control wild‐type ATDC5 cells or those containing a non‐coding shRNA. In addition, FLRT2 knockdown cells formed numerous lectin peanut agglutinin (PNA) stained aggregates and exhibited higher expression of the cell adhesion molecule, N‐cadherin. In an in vitro wound healing assay, fewer FLRT2 knockdown cells appeared to migrate into the defect. Surprisingly, the FLRT2 knockdown cells demonstrated increased formation of Alcian blue‐stainable extracellular matrix, suggesting that their reduced aggregate formation did not inhibit subsequent chondrogenic differentiation. The opposite trends were observed in ATDC5 clones that overexpressed FLRT2. Specifically, FLRT overexpressing cells proliferated faster, formed fewer PNA‐positive aggregates, accumulated increased Alcian blue‐positive matrix, and migrated faster to close a wound. Collectively, our findings provide evidence for a role of FLRT2 in enhancing cell proliferation and reducing intercellular adhesion during the early stages of chondrogenesis. J. Cell. Biochem. 112: 3440–3448, 2011. © 2011 Wiley Periodicals, Inc.
Mammary adipocytes bioactivate 25‐hydroxyvitamin D3 and signal via vitamin D3 receptor, modulating mammary epithelial cell growth
Authors: Ching Stephen , Kashinkunti Soumya , Niehaus Matthew D. , Zinser Glendon M.
Published: July 2011

The vitamin D3 receptor (VDR) is present in all microenvironments of the breast, yet it is hypothesized to signal through the epithelium to regulate hormone induced growth and differentiation. However, the influence or contribution of the other microenvironments within the breast that express VDR, like the breast adipose tissue, are yet to be investigated. We hypothesized that the breast adipocytes express the signaling components necessary to participate in vitamin D3 synthesis and signaling via VDR, modulating ductal epithelial cell growth and differentiation. We utilized human primary breast adipocytes and VDR wild type (WT) and knockout (KO) mice to address whether breast adipocytes participate in vitamin D3‐induced growth regulation of the ductal epithelium. We report in this study that breast primary adipocytes express VDR, CYP27B1 (1α‐hydroxylase, 1α‐OHase), the enzyme that generates the biologically active VDR ligand, 1α,25‐dihydroxyvitamin D3 (1,25D3), and CYP24 (24‐hydroxylase, 24‐OHase), a VDR‐1,25D3 induced target gene. Furthermore, the breast adipocytes participate in bioactivating 25‐hydroxyvitamin D3 (25D3) to the active ligand, 1,25D3, and secreting it to the surrounding microenvironment. In support of this concept, we report that purified mammary ductal epithelial fragments (organoids) from VDR KO mice, co‐cultured with WT breast adipocytes, were growth inhibited upon treatment with 25D3 or 1,25D3 compared to vehicle alone. Collectively, these results demonstrate that breast adipocytes bioactivate 25D3 to 1,25D3, signal via VDR within the adipocytes, and release an inhibitory factor that regulates ductal epithelial cell growth, suggesting that breast adipose tissue contributes to vitamin D3‐induced growth regulation of ductal epithelium. J. Cell. Biochem. 112: 3393–3405, 2011. © 2011 Wiley Periodicals, Inc.
Downregulation of p57kip2 promotes cell invasion via LIMK/cofilin pathway in human nasopharyngeal carcinoma cells
Authors: Chow Shu‐Er , Wang Jong‐Shyan , Lin Ming‐Rung , Lee Chien Lin
Published: July 2011

The members of Rho family are well known for their regulation of actin cytoskeleton to control cell migration. The Cip/kip members of cyclin‐dependent (CDK) inhibitors have shown to implicate in cell migration and cytoskeletal dynamics. p57kip2, a CDK inhibitor, is frequently down‐regulated in several malignancy tumors. However, its biological roles in human nasopharyngeal carcinoma (NPC) cells remained to be investigated. Here, we found p57kip2 has nuclear and cytoplasm distributions and depletion of endogenous p57kip2 did not change the cell‐cycle progression. Inhibition of cell proliferation by mitomycin C promoted FBS‐mediated cell migration and accompanied with the downregulation of ΔNp63α and p57kip2, but did not change the level of p27kip1, another CDK inhibitor. By using siRNA transfection and cell migration/invasion assays, we found that knockdown of p57kip2, but not ΔNp63α, involved in promotion of NPC cell migration and invasion via decrease of phospho‐cofilin (p‐cofilin). Treatment with Y‐27632, a specific ROCK inhibitor, we found that dysregulation of ROCK/cofilin pathway decreased p‐cofilin expression and induced cell migration. This change of p‐cofilin induced actin remodeling and pronounced increase of membrane protrusions. Further, silence of p57kip2 not only decreased the interaction between p57kip2 and LIMK‐1 assayed by immunoprecipitation but also reduced the level of phospho‐LIMK1/2. Therefore, this study indicated that dysregulation of p57kip2 promoted cell migration and invasion through modulation of LIMK/cofilin signaling and suggested this induction of inappropriate cell motility might contribute to promoting tumor cell for metastasis. J. Cell. Biochem. 112: 3459–3468, 2011. © 2011 Wiley Periodicals, Inc.
MYC accelerates p21CIP‐induced megakaryocytic differentiation involving early mitosis arrest in leukemia cells
Authors: Muñoz‐Alonso María J. , Ceballos Laura , Bretones Gabriel , Frade Pilar , León Javier , Gandarillas Alberto
Published: July 2011

p21CIP is a potent cell cycle inhibitor often up‐regulated in differentiation. Protooncogene MYC induces cell growth and proliferation, inhibits differentiation and represses p21CIP. However, both molecules are involved in processes of polyploidisation, cell size increase, differentiation and senescence. It is unclear why MYC has a dual role in differentiation. We have previously shown that overexpression of p21CIP in K562 myeloid cells induces megakaryocytic differentiation with polyploidy. We have now investigated the requirements for p21CIP to block mitosis and induce differentiation in the presence of overactivated MYC. Silencing and over‐expression studies showed that p21CIP is required to induce differentiation. However, the expression of p21CIP needs to be transient to irreversibly inhibit mitosis but not DNA replication, what leads to polyploidy. Transient overexpression of p21CIP caused early down‐regulation of mitotic Cyclins and up‐regulation of G1/S Cyclins D and E, changes typical of endoreplication. Interestingly, over‐activation of MYC did not release the proliferative block imposed by p21CIP and instead, accelerated cell size increase, megakaryocytic differentiation and polyploidisation. Our data suggests that in some systems p21CIP takes part in a mitosis control driving MYC‐induced cellular growth into differentiation. J. Cell. Physiol. 227: 2069–2078, 2012. © 2011 Wiley Periodicals, Inc.
Branched‐chain amino acids prevent insulin‐induced hepatic tumor cell proliferation by inducing apoptosis through mTORC1 and mTORC2‐dependent mechanisms
Authors: Hagiwara Asami , Nishiyama Megumi , Ishizaki Sonoko
Published: July 2011

Branched‐chain amino acids (BCAA) supplementation has been reported to suppress the incidence of liver cancer in obese patients with liver cirrhosis or in obese and diabetic model animals of carcinogenesis. Whether BCAA directly suppresses cell proliferation of hepatic tumor cells under hyperinsulinemic condition remain to be defined. The aim of this study was to investigate the effects of BCAA on insulin‐induced proliferation of hepatic tumor cells and determine the underlying mechanisms. BCAA suppressed insulin‐induced cell proliferation of H4IIE, HepG2 cells. In H4IIE cells, BCAA did not affect cell cycle progression but increased apoptosis by suppressing expressions of anti‐apoptotic genes and inducing pro‐apoptotic gene via inactivation of PI3K/Akt and NF‐κB signaling pathways. Further studies demonstrated that BCAA inhibited PI3K/Akt pathway not only by promoting negative feedback loop from mammalian target of rapamycin complex 1 (mTORC1)/S6K1 to PI3K/Akt pathway, but also by suppressing mTORC2 kinase activity toward Akt. Our findings suggest that BCAA supplementation may be useful to suppress liver cancer progression by inhibiting insulin‐induced PI3K/Akt and subsequent anti‐apoptotic pathway, indicating the importance of BCAA supplementation to the obese patients with advanced liver disease. J. Cell. Physiol. 227: 2097–2105, 2012. © 2011 Wiley Periodicals, Inc.
Brain‐derived neurotrophic factor induces migration of endothelial cells through a TrkB–ERK–integrin αVβ3–FAK cascade
Authors: Matsuda Shinji , Fujita Tsuyoshi , Kajiya Mikihito , Takeda Katsuhiro , Shiba Hideki , Kawaguchi Hiroyuki , Kurihara Hidemi
Published: July 2011

Brain‐derived neurotrophic factor (BDNF) promotes the regeneration of periodontal tissue. Since angiogenesis is important for tissue regeneration, investigating effect of BDNF on endothelial cell function may help to reveal its mechanism, whereby, BDNF promotes periodontal tissue regeneration. In this study, we examined the influence of BDNF on migration in human microvascular endothelial cells (HMVECs), focusing on the effects on extracellular signal‐regulated kinase (ERK), integrin αVβ3, and focal adhesion kinase (FAK). The migration of endothelial cells was assessed with a modified Boyden chamber and a wound healing assay. The expression of integrin αVβ3 and the phosphorylation of ERK and FAK were analyzed by immunoblotting and immunofluorescence microscopy. BDNF (25 ng/ml) induced cell migration. PD98059, an ERK inhibitor, K252a, a specific inhibitor for TrkB, a high affinity receptor of BDNF, and an anti‐integrin αVβ3 antibody suppressed the BDNF‐induced migration. BDNF increased the levels of integrin αVβ3 and phosphorylated ERK1/2 and FAK. The ERK inhibitor and TrkB inhibitor also reduced levels of integrin αVβ3 and phosphorylated FAK. We propose that BDNF stimulates endothelial cell migration by a process involving TrkB/ERK/integrin αVβ3/FAK, and this may help to enhance the regeneration of periodontal tissue. J. Cell. Physiol. 227: 2123–2129, 2012. © 2011 Wiley Periodicals, Inc.