bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal indication of cannabis use by means of THC glucuronide determination
Authors: Mareck Ute , Haenelt Nadine , Geyer Hans , Guddat Sven , Kamber Matthias , Brenneisen Rudolf , Thevis Mario , Schänzer Wilhelm
Published: January 2010

According to the regulations of the World Anti‐Doping Agency (WADA), the use of cannabinoids is forbidden in competition. In doping controls, the detection of cannabinoid misuse is based on the analysis of the non‐psychoactive metabolite 11‐nor‐9‐carboxy‐delta‐9‐tetrahydrocannabinol (carboxy‐THC). The determination of values greater than 15 ng/mL in urine represents an adverse analytical finding; however, no accurate prediction of the time of application is possible as the half‐life of carboxy‐THC ranges between three and four days. Consequently the detection of carboxy‐THC in doping control urine samples collected in competition might also result from cannabis use in out‐of‐competition periods. The analysis of the glucuronide of the pharmacologically active delta 9‐tetrahydrocannabinol (THC‐gluc) may represent a complementary indicator for the detection of cannabis misuse in competition.

An assay for the determination of THC‐gluc in human urine was established. The sample preparation consisted of liquid‐liquid extraction of urine specimens, and extracts were analysed by liquid chromatography/tandem mass spectrometry (LC‐MS/MS). Authentic doping‐control urine samples as well as specimens obtained from a controlled smoking study were analysed and assay characteristics such as specificity, detection limit (0.1 ng/mL), precision (>90%), recovery (∼80%), and extraction efficiency (90%) were determined. Copyright © 2010 John Wiley & Sons, Ltd.
Examining the combinatorial model of motor neuron survival by expression profiling of trophic factors and their receptors in the embryonic Gallus gallus
Authors: Gu Wendy X.W. , Kania Artur
Published: January 2010

During embryogenesis, limb‐innervating lateral motor column (LMC) spinal motor neurons (MN) are generated in excess and subsequently nearly half of them die. Many motor neuron survival factors (MnSFs) have been shown to suppress this default programmed cell death (PCD) program through their receptors (MnSFRs), raising the possibility that they are involved in matching specific MNs with their target muscles. Published observations suggest a combinatorial model of MnSF/Rs function, which assumes that during the PCD phase, MNs are expressing combinations of MnSFRs, whereas the limb muscles innervated by these MNs express cognate combinations of MnSFs. We tested this model by expression profiling of MnSFs and their receptors in the avian lumbosacral spinal cord and limb muscles during the peak PCD period. Our findings highlight the complexity of MnSF/Rs function in the control of LMC motor neuron survival. Developmental Dynamics 239:965–979, 2010. © 2010 Wiley‐Liss, Inc.
Fibromodulin regulates collagen fibrillogenesis during peripheral corneal development
Authors: Chen Shoujun , Oldberg Ake , Chakravarti Shukti , Birk David E.
Published: January 2010

Fibromodulin regulates collagen fibrillogenesis, but its existence/role(s) in the cornea is controversial. We hypothesize that fibromodulin regulates fibrillogenesis during postnatal development of the anterior eye. Fibromodulin is weakly expressed in the limbus at post‐natal day (P) 4, increases and extends into the central cornea at P14, becomes restricted to the limbus at P30, and decreases at P60. This differential spatial and temporal expression of fibromodulin is coordinated with emmetropization; the developmental increase in axial length and globe size. Genetic analysis demonstrated that fibromodulin regulates fibrillogenesis in a region‐specific manner. At the limbus, fibromodulin is dominant in regulating fibril growth during postnatal development. In the posterior peripheral cornea, cooperative interactions of fibromodulin and lumican regulate fibrillogenesis. These data indicate that fibromodulin plays important roles in the regulation of region‐specific fibrillogenesis required for the integration of the corneal and scleral matrices and sulcus development required for establishment of the visual axis. Developmental Dynamics 239:844–854, 2010. © 2010 Wiley‐Liss, Inc.
The role of cell cycle in retinal development: Cyclin‐dependent kinase inhibitors co‐ordinate cell‐cycle inhibition, cell‐fate determination and differentiation in the developing retina†
Authors: Bilitou Aikaterini , Ohnuma Shin‐ichi
Published: January 2010

The mature retina is formed through multi‐step developmental processes, including eye field specification, optic vesicle evagination, and cell‐fate determination. Co‐ordination of these developmental events with cell‐proliferative activity is essential to achieve formation of proper retinal structure and function. In particular, the molecular and cellular dynamics of the final cell cycle significantly influence the identity that a cell acquires, since cell fate is largely determined at the final cell cycle for the production of postmitotic cells. This review summarizes our current understanding of the cellular mechanisms that underlie the co‐ordination of cell‐cycle and cell‐fate determination, and also describes a molecular role of cyclin‐dependent kinase inhibitors (CDKIs) as co‐ordinators of cell‐cycle arrest, cell‐fate determination and differentiation. Developmental Dynamics 239:727–736, 2010. © 2010 Wiley‐Liss, Inc.
Developmental biomarkers of aging in Caenorhabditis elegans
Authors: Pincus Zachary , Slack Frank J.
Published: January 2010

The developmental process of the nematode Caenorhabditis elegans is famously invariant; however, these animals have surprisingly variable lifespans, even in extremely homogenous environments. Inter‐individual differences in muscle‐function decline, accumulation of lipofuscin in the gut, internal growth of food bacteria, and ability to mobilize heat‐shock responses all appear to be predictive of a nematode's remaining lifespan; whether these are causal, or mere correlates of individual decline and death, has yet to be determined. Moreover, few “upstream” causes of inter‐individual variability have been identified. It may be the case that variability in lifespan is entirely due to stochastic damage accumulation; alternately, perhaps such variability has a developmental origin and/or genes involved in developmental canalization also act to buffer phenotypic heterogeneity later in life. We review these two hypotheses with an eye toward whether they can be experimentally differentiated. Developmental Dynamics 239:1306–1314, 2010. © 2010 Wiley‐Liss, Inc.
Non‐apoptotic cell death in Caenorhabditis elegans
Authors: Vlachos Manolis , Tavernarakis Nektarios
Published: January 2010

The simple nematode worm Caenorhabditis elegans has been instrumental in deciphering the molecular mechanisms underlying apoptosis. Beyond apoptosis, several paradigms of non‐apoptotic cell death, either genetically or extrinsically triggered, have also been described in C. elegans. Remarkably, non‐apoptotic cell death in worms and pathological cell death in humans share numerous key features and mechanistic aspects. Such commonalities suggest that similarly to apoptosis, non‐apoptotic cell death mechanisms are also conserved, and render the worm a useful organism, in which to model and dissect human pathologies. Indeed, the genetic malleability and the sophisticated molecular tools available for C. elegans have contributed decisively to advance our understanding of non‐apoptotic cell death. Here, we review the literature on the various types of non‐apoptotic cell death in C. elegans and discuss the implications, relevant to pathological conditions in humans. Developmental Dynamics 239:1337–1351, 2010. © 2010 Wiley‐Liss, Inc.
Effect of Water Concentration and Acidity on the Synthesis of Porous Chromium Benzenedicarboxylates
Authors: Khan Nazmul Abedin , Jun Jong Won , Jhung Sung Hwa
Published: January 2010

In the present work, two metal–organic frameworks (MOFs), chromium benzenedicarboxylates MIL‐53 and MIL‐101, have been synthesized. A wide range of reaction conditions were explored in order to understand the effects of water concentration and acidity. It was found that MIL‐101 is preferentially obtained when the water content is high and the acidity is low. On the contrary, concentrated reactants and high acidity lead to the formation of MIL‐53. The steady conversion of MIL‐101 into MIL‐53 during the reaction, due to the difference in relative stability, was also confirmed. The effect of water may therefore be explained by the increase in reaction rate with increasing concentration of reactants. The MIL‐53 is selectively obtained at low water content, because the MIL‐101, a transient phase, even if formed initially, may be converted into MIL‐53 because of the high reaction rate. Relatively low acidity (a pH of about 3) is beneficial to the synthesis of MIL‐101 even though increased MIL‐53 yield was expected at low acidity due to the accelerated deprotonation of terephthalic acid. The selective formation of MIL‐101 at low acidity is probably because the concentration of a chromium trimer (the chromium species that is essential for the MIL‐101 structure) increases with increasing pH. The concentration of the Cr trimer is more important than the concentration of benzenedicarboxylate for the synthesis of MIL‐101.
Synthesis of α‐Alkynyl‐β,β,β‐trifluoroalanine Derivatives by Sonogashira Cross‐Coupling Reaction
Authors: Shchetnikov Grigorii T. , Zotova Maria A. , Bruneau Christian , Dixneuf Pierre H. , Osipov Sergey N.
Published: January 2010

An efficient route to new α‐CF3‐α‐amino acid derivatives bearing an arylalkynyl moiety at the α‐carbon atom has been developed. The method is based on palladium‐catalyzed cross‐coupling of the corresponding α‐propargyl (ethynyl) α‐amino esters with aryl halides to afford the amino acid derivatives with an internal triple bond that is suitable for further modifications.
A Facile Synthesis of Lentiginosine Analogues Based on a Highly Regio‐ and Diastereoselective Allylic Amination Using Chlorosulfonyl Isocyanate
Authors: Kim In Su , Li Qing Ri , Dong Guang Ri , Kim Yoo Chang , Hong Yeon Ju , Lee Momi , Chi Ki‐Whan , Oh Joa Sub , Jung Young Hoon
Published: January 2010

The concise synthesis of the lentiginosine analogues pyrrolizidine alkaloid 2 and pyrroloazepine alkaloid 3 has been achieved from inexpensive and readily available D‐lyxose. The key steps in the synthesis included regio‐ and diastereoselective amination, inter‐ or intramolecular olefin metathesis, and Appel cyclization. The anti‐3,4‐amino alcohol 6, essential for the preparation of the title compounds 2 and 3, was synthesized by the regio‐ and diastereoselective amination of anti‐3,4‐tribenzyl ether 7 using chlorosulfonyl isocyanate. The reaction of 7 with chlorosulfonyl isocyanate in toluene at 0 °C afforded 6 exclusively with a diastereoselectivity of 26:1 in 84 % yield. These results can be explained by the neighboring‐group effect, which leads to retention of thestereochemistry.
Elucidating the identity of Anisakis larvae from a broad range of marine fishes from the Yellow Sea, China, using a combined electrophoretic‐sequencing approach
Authors: Du Chunxia , Zhang Luping , Shi Meiqing , Ming Zhu , Hu Min , Gasser Robin B.
Published: January 2010

Larval nematodes were collected from marine fishes from the Yellow Sea, China. Specimens (n=1731) of Anisakis type I from 311 fishes (representing 40 species) were each identified based on morphological characters. From the genomic DNA from individual specimens, a region of nuclear ribosomal DNA was amplified by PCR, followed by digestion with restriction endonuclease HinfI, TaqI or HhaI. Subsequently, the ITS‐1 and ITS‐2 regions of selected samples were sequenced. The results revealed three species of Anisakis, namely Anisakis pegreffii (n=1709), A. typica (n=3) and a genotype (n=19) proposed, also based on comparison with previous studies, to be a “hybrid” between A. pegreffii and A. simplex sensu stricto. Thus, A. pegreffii was the dominant species, accounting for 98.7% of the total number of specimens examined herein. This is the first report of A. typica and the “hybrid” genotype from fishes from the Yellow Sea. This study provides important basic information on Anisakis in this region and suggests that the genus Anisakis has substantial host and geographical distributions.
Determination of malachite green in fish water samples by cloud‐point extraction coupled to cation‐selective exhaustive injection and sweeping‐MEKC
Authors: Luo Xubiao , Jiang Xin , Tu Xinman , Luo Shenglian , Yan Liushui , Chen Bo
Published: January 2010

We have employed a high‐sensitivity off‐line coupled with on‐line preconcentration method, cloud‐point extraction (CPE)/cation‐selective exhaustive injection (CSEI) and sweeping‐MEKC, for the analysis of malachite green. The variables that affect CPE were investigated. The optimal conditions were 250 g/L of Triton X‐100, 10% of Na2SO4 (w/v), heat‐assisted at 60°C for 20 min. We monitored the effects of several of the CSEI‐sweeping‐MEKC parameters – including the type of BGE, the concentrations of SDS, the injection length of the high‐conductivity buffer, and the injection time of the sample – to optimize the separation process. The optimal BGE was 50 mM citric acid (pH 2.2) containing 100 mM SDS. In addition, electrokinetic injection of the sample at 15 kV for 800 s provided both high separation efficiency and enhanced sweeping sensitivity. The sensitivity enhancement for malachite green was 1.9×104 relative to CZE; the coefficients of determination exceeded 0.9928. The LOD, based on an S/N of 3:1, of CSEI‐sweeping‐MEKC was 0.87 ng/mL; in contrast, when using off‐line CPE/CSEI‐sweeping‐MEKC the sensitivity increased to 69.6 pg/mL. This proposed method was successfully applied to determine trace amounts of malachite green in fish water samples.
A tale of two planets: geomorphology applied to Mars' surface, fluvio‐deltaic processes and landforms
Authors: Kleinhans Maarten G.
Published: January 2010

Deltas on planet Mars record past climate, but so far a wide range of hypotheses for their formation have been proposed. The objective of this paper is to understand martian fan deltas, their formative conditions, evolution and formative duration, and implications for the past climate.

As an introduction to Mars, physiographic provinces are described and unambiguous proof is listed for the presence of flowing water in the past, such as certain minerals, groundwater, catastrophic outflow channels, alluvial fans and fan deltas, distributary networks and glaciers. The climate history of Mars differs from that of Earth by having had much drier conditions than on Earth, extreme intermittency and extreme events, most of them billions of years ago.

Tens of fan deltas, unchannelized fan deltas and stepped fans have been found in impact crater and other lakes. The stepped fans were likely formed by backstepping under fast rising lake levels and have no known terrestrial equivalent. The fan deltas were formed once the lake overflowed. Alluvial fans are much more numerous and formed with less water.

The delta studies illustrate how major challenges of martian morphology and reconstruction of past conditions can be taken up most effectively by combinations of the available high‐resolution images and digital elevation models, terrestrial analogues, laboratory experiments and physics‐based models gleaned from geomorphology.

To resolve formative mechanisms and time scale of martian fans and deltas, morphological distinctions between dense debris flows and dilute fluvial flows must be identified for both source and sink areas. Furthermore, the properties of the martian surface material are very poorly constrained but can be explored by modelling various mass wasting, fluvial and glacial phenomena and hydrology, and by experimentation with slightly cohesive sediment. Finally, the highly debated role of groundwater sapping in valley and delta formation on Mars should be explored experimentally. Copyright © 2010 John Wiley & Sons, Ltd.
Lithological and fluvial controls on the geomorphology of tropical montane stream channels in Puerto Rico
Authors: Pike Andrew S. , Scatena Frederick N. , Wohl Ellen E.
Published: January 2010

An extensive survey and topographic analysis of five watersheds draining the Luquillo Mountains in north‐eastern Puerto Rico was conducted to decouple the relative influences of lithologic and hydraulic forces in shaping the morphology of tropical montane stream channels. The Luquillo Mountains are a steep landscape composed of volcaniclastic and igneous rocks that exert a localized lithologic influence on the stream channels. However, the stream channels also experience strong hydraulic forcing due to high unit discharge in the humid rainforest environment. GIS‐based topographic analysis was used to examine channel profiles, and survey data were used to analyze downstream changes in channel geometry, grain sizes, stream power, and shear stresses. Results indicate that the longitudinal profiles are generally well graded but have concavities that reflect the influence of multiple rock types and colluvial‐alluvial transitions. Non‐fluvial processes, such as landslides, deliver coarse boulder‐sized sediment to the channels and may locally determine channel gradient and geometry. Median grain size is strongly related to drainage area and slope, and coarsens in the headwaters before fining in the downstream reaches; a pattern associated with a mid‐basin transition between colluvial and fluvial processes. Downstream hydraulic geometry relationships between discharge, width and velocity (although not depth) are well developed for all watersheds. Stream power displays a mid‐basin maximum in all basins, although the ratio of stream power to coarse grain size (indicative of hydraulic forcing) increases downstream. Excess dimensionless shear stress at bankfull flow wavers around the threshold for sediment mobility of the median grain size, and does not vary systematically with bankfull discharge; a common characteristic in self‐forming ‘threshold’ alluvial channels. The results suggest that although there is apparent bedrock and lithologic control on local reach‐scale channel morphology, strong fluvial forces acting over time have been sufficient to override boundary resistance and give rise to systematic basin‐scale patterns. Copyright © 2010 John Wiley and Sons, Ltd.
Power quality state estimation
Authors: Watson Neville R.
Published: January 2010

Due to the size and complexity of modern electrical power networks and the cost of monitoring and telecommunication equipment, it is unfeasible to fully monitor the system state. For this reason state estimation techniques are used. With strategically placed measurements, estimation techniques can determine the parameters at unmonitored locations. Fundamental frequency state estimation is now a standard tool in modern power systems. The emission and immunity levels of modern electrical equipment are different to that of the past, and this has resulted in power quality issues have become important. Knowledge of the source and location of the disturbances is desirable so that remedial action can be taken promptly. Recent contributions have extended the concept to: harmonic state estimation (HSE) and identification of harmonic sources, transient state estimation (TSE) and voltage sag state estimation (VSSE), which are all types of power quality state estimation (PQSE). This paper provides an overview of the state‐of‐the‐art techniques currently available for PQSE in a large electrical power system. Copyright © 2009 John Wiley & Sons, Ltd.
Pt and Sn Doped Sputtered CeO2 Electrodes for Fuel Cell Applications
Authors: Matolín V. , Cabala M. , Matolínová I. , Škoda M. , Václavů M. , Prince K.C. , Skála T. , Mori T. , Yoshikawa H. , Yamashita Y. , Ueda S. , Kobayashi K.
Published: January 2010

The interaction of Pt with CeO2 layers was investigated by using photoelectron spectroscopy. Thirty‐nanometre‐thick Pt and Sn doped CeO2 layers were deposited simultaneously by rf‐magnetron sputtering on a Si(001) substrate and a carbon diffusion layer of a polymer membrane fuel cell by using a composite CeO2–Pt–Sn target. The laboratory XPS and synchrotron radiation soft X‐ray and hard X‐ray photoemission spectra showed the formation of cerium oxide with completely ionised Pt2+,4+ species, and with Pt4+ embedded in the film bulk. Hydrogen/air fuel cell activity measurements normalised to the amount of Pt used revealed high specific power of up to 5.4 × 104 mW mg–1 (Pt). The activity of these materials is explained by the strong activity of embedded Ptn+ cations.
The early news catches the attention: On the relative price impact of similar economic indicators
Authors: Hess Dieter , Niessen Alexandra
Published: January 2010

This study investigates why financial markets react to the release of some economic indicators while ignoring others with similar informational content. Based on a Bayesian learning model, we show that the market impact of an economic indicator depends crucially on its early availability. The sequential introduction of the two largest German business surveys provides a natural experiment by which the model's implications are tested empirically. We show that even a large and well‐established indicator loses market impact if a similar indicator is launched and released earlier. © 2009 Wiley Periodicals, Inc. Jrl Fut Mark 30:909–937, 2010
Sustained Virologic Response Prevents the Development of Esophageal Varices in Compensated, Child-Pugh Class A Hepatitis C Virus–Induced Cirrhosis. A 12-Year Prospective Follow-Up Study
Authors: Bruno Savino , Crosignani Andrea , Facciotto Corinna , Rossi Sonia , Roffi Luigi , Redaelli Alessandro , de Franchis Roberto , Almasio Piero Luigi , Maisonneuve Patrick
Published: January 2010

The incidence of

de novo

development of esophageal varices (EV) in patients with compensated liver cirrhosis has been determined by few studies in the short term and never in the long term. The aims of the present study were to determine the incidence and the risk factors associated with the development of EV and to assess whether antiviral treatment and achievement of sustained virologic response (SVR) may prevent

de novo

EV development in patients with HCV-induced cirrhosis. We studied 218 patients with compensated EV-free, HCV-induced cirrhosis consecutively enrolled between 1989 and 1992 at three referral centers in Milan, Italy. Endoscopic surveillance was performed at 3-year intervals according to international guidelines. SVR was defined as undetectable serum HCV-RNA 24 weeks after treatment discontinuation. During a median follow-up of 11.4 years, 149/218 (68%) patients received antiviral treatment and 34 (22.8%) achieved SVR. None of the SVR patients developed EV compared with 22 (31.8%) of the 69 untreated subjects (

P

< 0.0001) and 45 (39.1%) of the 115 non-SVR patients (

P

< 0.0001). On multivariate analysis, HCV genotype 1b (hazard ratio [HR] 2.40; 95% confidence interval [CI] 1.17-4.90) and baseline model for end-stage liver disease (MELD) score (HR 1.20; 95% CI 1.07-1.35 for 1 point increase) were independent predictors of EV.

Conclusion:

In the long term, the achievement of SVR prevents the development of EV in patients with compensated HCV-induced cirrhosis. Therefore, in these patients, endoscopic surveillance can be safely delayed or avoided. Genotype 1b infection and MELD score identify the subset of patients at higher risk of EV development who need tailored endoscopic surveillance. Hepatology 2010
Spred2 inhibits TGF‐β1‐induced urokinase type plasminogen activator expression, cell motility and epithelial mesenchymal transition
Authors: Villar Victor , Kocić Jelena , Santibanez Juan F.
Published: January 2010

TGF‐β1 is a potent inductor of malignance in cancer cells. TGF‐β1 stimulates the expression of extracellular matrix degrading proteases, cell migration and it is also involved in the epithelial‐mesenchymal transition (EMT). In the present work, we analyzed the role of Spred2 in the urokinase‐type plasminogen activator (uPA) stimulation, EMT and cell migration by TGF‐β1. We found that both the expression of mRNA and the protein level of Spred2 were lower in transformed keratinocytes PDV compared with immortalized keratinocytes MCA‐3D. The transient ectopic expression of Spred2 in PDV cells inhibited the TGF‐β1‐transactivated SRE‐Luc reporter which is related with the ERK1,2 signal. The stable ectopic expression of Spred2 in PDV cells (SP cells) led to the loss of ERK 1,2 activation by TGF‐β1, although Smad2 activation was not affected, and the knockdown of Spred2 enhanced the activation of ERK1,2 signal by TGF‐β1. The increment of uPA expression induced by TGF‐β1 was suppressed in SP cells. In contrast, the stimulus on PAI‐1 expression was not affected and comparable to parental PDV cells. SP cells under TGF‐β1 treatment were unable to display the EMT, since the overexpression of Spred2 abolished the TGF‐β1‐induced disruption of the E‐cadherin cell to cell interactions, reorganization of the actin cytoskeleton and upregulation of the mesenchymal marker vimentin. Finally, SP cells could not respond to the TGF‐β1 stimulus on cell migration. Taken together, the data in the present study suggests that Spred2 is a regulator of TGF‐β1‐induced malignance in transformed keratinocytes.
Realising the future: forecasting with high‐frequency‐based volatility (HEAVY) models
Authors: Shephard Neil , Sheppard Kevin
Published: January 2010

This paper studies in some detail a class of high‐frequency‐based volatility (HEAVY) models. These models are direct models of daily asset return volatility based on realised measures constructed from high‐frequency data. Our analysis identifies that the models have momentum and mean reversion effects, and that they adjust quickly to structural breaks in the level of the volatility process. We study how to estimate the models and how they perform through the credit crunch, comparing their fit to more traditional GARCH models. We analyse a model‐based bootstrap which allows us to estimate the entire predictive distribution of returns. We also provide an analysis of missing data in the context of these models. Copyright © 2010 John Wiley & Sons, Ltd.
Interaction of Sedlin with PAM14
Authors: Liu Xiaoying , Wang Yunfei , Zhu Hengrui , Zhang Qinghui , Xing Xin , Wu Biao , Song Lihua , Fan Libin
Published: January 2010

Sedlin is an evolutionarily conserved and ubiquitously expressed protein that is encoded by the gene SEDL. Mutations in the latter are known to be causative for spondyloepiphyseal dysplasia tarda. However, the mechanism underlying this remains unclear. We have previously shown that Sedlin interacts with the intracellular chloride channel proteins CLIC1 and CLIC2 in the cytoplasm. In this report we show that Sedlin is also physically associated with protein associated with MRG 14 kDa (PAM14), a nuclear protein that interacts with the transcription factor MORF4‐related gene on chromosome 15 (MRG15). This was suggested by yeast two‐hybrid screening and was confirmed with GST pull‐down and immunoprecipitation assays. Moreover, we demonstrate that the C‐terminus of Sedlin and the N‐terminus of PAM14 are critical for their interaction. Together, these results suggest that nucleus‐localized Sedlin may play a role in regulation of transcriptional activities of the MRG family of transcription factors via binding to PAM14. J. Cell. Biochem. 109: 1129–1133, 2010. © 2010 Wiley‐Liss, Inc.
Apoptosis‐inducing effect of garcinol is mediated by NF‐κB signaling in breast cancer cells
Authors: Ahmad Aamir , Wang Zhiwei , Ali Raza , Maitah Ma'in Y. , Kong Dejuan , Banerjee Sanjeev , Padhye Subhash , Sarkar Fazlul H.
Published: January 2010

Garcinol, obtained from Garcinia indica in tropical regions, is used for its numerous biological effects. Its anti‐cancer activity has been suggested but the mechanism of action has not been studied in‐detail, especially there is no report on its action against breast cancer cells. Here we tested our hypothesis that garcinol may act as an anti‐proliferative and apoptosis‐inducing agent against breast cancer cell lines. Using multiple techniques such as MTT, Histone‐DNA ELISA, Annexin V‐PI staining, Western blot for activated caspases and cleaved PARP, homogenous caspase‐3/7 fluorometric assay and EMSA, we investigated the mechanism of apoptosis‐inducing effect of garcinol in ER‐positive MCF‐7 and ER‐negative MDA‐MB‐231 cells. We found that garcinol exhibits dose‐dependent cancer cell‐specific growth inhibition in both the cell lines with a concomitant induction of apoptosis, and has no effect on non‐tumorigenic MCF‐10A cells. Our results suggested induction of caspase‐mediated apoptosis in highly metastatic MDA‐MB‐231 cells by garcinol. Down‐regulation of NF‐κB signaling pathway was observed to be the mechanism of apoptosis‐induction. Garcinol inhibited constitutive NF‐κB activity, which was consistent with down‐regulation of NF‐κB‐regulated genes. This is the first report on anti‐proliferative and apoptosis‐inducing action of garcinol against human breast cancer cells and the results suggest that this natural compound merits investigation as a potential chemo‐preventive/‐therapeutic agent, especially against breast cancer. J. Cell. Biochem. 109: 1134–1141, 2010. © 2010 Wiley‐Liss, Inc.
Distinct mechanosensitive Ca2+influx mechanisms in human primary synovial fibroblasts
Authors: Sakamoto Yuko , Ishijima Muneaki , Kaneko Haruka , Kurebayashi Nagomi , Ichikawa Naoki , Futami Ippei , Kurosawa Hisashi , Arikawa‐Hirasawa Eri
Published: January 2010

Synovial cells are exposed to continually changing dynamic forces and are implicated in the maintenance of joint homeostasis. However, the mechanisms of synovial cell responses to mechanical stress are unclear. In this study, we investigated the difference between the mechanosensitive channels of human primary synovial fibroblasts (SFBs) and human primary dermal fibroblasts (DFBs) in response to mechanical stretch by uniaxial cyclic stretching and mechanical cell membrane deformation in vitro. Cyclic stretching induced orientation of SFBs and DFBs perpendicularly to the stretching direction. Furthermore, uniaxial stretching increased intracellular Ca2+levels in both cell types. The perpendicular orientation of DFBs was blocked by gadolinium (III) chloride (Gd3+, a mechanosensitive Ca2+channel blocker) or ruthenium red (RR, a nonselective Ca2+channel blocker). However, Gd3+did not block the stretch‐induced perpendicular orientation in SFBs, while RR inhibited this orientation. Similarly, Ca2+influx in DFBs induced by uniaxial stretching and membrane deformation was inhibited by Gd3+, RR, and GsMTx‐4 (another mechanosensitive Ca2+channel blocker), while only RR inhibited Ca2+influx in SFBs. Our results suggest that SFBs respond to mechanical stretch through mechanosensitive channels that are distinct from those of DFBs. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:859–864, 2010
Intraneural blood flow analysis during an intraoperative Phalen's test in carpal tunnel syndrome
Authors: Yayama Takafumi , Kobayashi Shigeru , Awara Kousuke , Takeno Kenichi , Miyazaki Tsuyoshi , Kubota Masafumi , Negoro Kohei , Baba Hisatoshi
Published: January 2010

Phalen's test has been one of the most significant of clinical signs when making a clinical diagnosis of idiopathic carpal tunnel syndrome (CTS). However, it is unknown whether intraneural blood flow changes during Phalen's test in patients with CTS. In this study, an intraoperative Phalen's test was conducted in patients with CTS to observe the changes in intraneural blood flow using a laser Doppler flow meter. During Phalen's test, intraneural blood flow showed a sharp decrease, which lasted for 1 min. Intraneural blood flow decreased by 56.7%–100% (average, 78.0%) in the median nerve relative to the blood flow before the test. At 1 min after completing the test, intraneural blood flow returned to the baseline value. After carpal tunnel release, there was no marked decrease in intraneural blood flow. This study demonstrated that the blood flow in the median nerve is reduced when Phalen's test is performed in vivo. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1022–1025, 2010
Comparison of differential biomarkers of osteoarthritis with and without posttraumatic injury in the Hartley guinea pig model
Authors: Wei Lei , Fleming Braden C. , Sun Xiaojuan , Teeple Erin , Wu Wesley , Jay Gregory D. , Elsaid Khaled A. , Luo Junming , Machan Jason T. , Chen Qian
Published: January 2010

The objective was to compare biomarkers of articular cartilage metabolism in synovial fluid from Hartley guinea pig knees, with and without anterior cruciate ligament transection (ACLT), to establish whether detectable differences in biomarker levels exist between primary and secondary osteoarthritis (OA). Synovial fluid lavages and knees were obtained from 3‐month (control group) and 12‐month (primary OA group) animals. Another group of animals (posttraumatic OA group) underwent unilateral ACLT at 3 months, and samples were obtained 9 months postsurgery. Synovial fluid concentrations of stromal cell‐derived‐factor (SDF‐1), collagen fragments (C2C), proteoglycan (GAG), lubricin, matrix metalloproteinase‐13 (MMP‐13), and Interleukin‐1 (IL‐1β) were evaluated. Cartilage damage was assessed via histology. The highest concentrations of C2C and SDF‐1 in synovial fluid were found in the posttraumatic OA group, moderate concentrations were found in the primary OA group, and low concentrations in the control group. GAG release in synovial fluid was similar to C2C and SDF‐1. The lubricin concentrations were significantly lower in ACLT joints than either the control or 12‐month primary OA groups, but not between the control and primary OA groups. Higher levels of MMP‐13 and IL‐1β were detected in the joints of the posttraumatic OA group as compared to the control or primary OA groups. Histology revealed greatest OA damage in the posttraumatic OA group, followed by moderate and minimal damage in primary OA and control groups, respectively. This study indicates that the biomarkers and progression of OA may differ in the Hartley guinea pig models with and without posttraumatic OA. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:900–906, 2010
Biphasic effects of interleukin‐1β on osteoblast differentiation in vitro
Authors: Lin Fu‐Hsiumg , Chang Jessica B. , McGuire Michael H. , Yee John A. , Brigman Brian E.
Published: January 2010

A rat calvarial cell model of osteoblast differentiation using the formation of bone nodules in vitro as an endpoint was used to assess the effects of IL‐1β on osteoblast differentiation. Short‐term treatment (2 days) with IL‐1β early in culture resulted in increased nodule number and size as well as calcium content in contrast to long‐term treatment (6 days) in cultures assessed at 10–12 days. This increase in bone formation was blocked by IL‐1 receptor antagonists. Short‐term treatment increased COX‐2, prostaglandin (PGE2), and iNOS production. Exogenous PGE2 with IL‐1β enhanced this effect. COX‐2 inhibitors, indomethacin and N‐39, blocked 50% of nodule formation. NO donor did not modify effects of IL‐1β, but iNOS inhibitor (1400W) partially blocked the effects. However, PGE2 and NO donors could not rescue the decreased nodule number resulting from long‐term IL‐1β treatment. The results of this study suggest a biphasic effect of IL‐1β on bone nodule formation activated by IL‐1β binding with IL‐1 receptors, and the anabolic effect of early short‐term treatment with IL‐1β is likely mediated by PGE without ruling out nitric oxide. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:958–964, 2010
Hydrogen bonding in the pyrimidine/ formamide system: a concentration‐dependent Raman and DFT study
Authors: Srivastava Sunil K. , Schlücker Sebastian , Alves Wagner A.
Published: January 2010

High‐resolution Raman spectra of pyrimidine (PD) and formamide (FA) mixtures with different compositions recorded in the ring breathing region of PD (ν1 ∼ 991 cm−1) are presented. The dilution of PD with FA leads to the appearance of a new band at ν1′ ∼ 994 cm−1, which is assigned to hydrogen‐bonded PD:FA species. From a quantitative analysis of the concentration‐dependent Raman spectra, the average number of FA molecules in the first solvation sphere of PD is determined as being equal to 2. This value is supported by density functional theory (DFT) calculations: a symmetric 1:2 complex is the most stable species among various hydrogen‐bonded PD:FA clusters with stoichiometries ranging from 1:1 to 1:4. A qualitative explanation for the blue shift of the ν1 mode upon complexation is given. Additionally, we have observed not only similarities but also some differences with respect to the PD:water system. Copyright © 2010 John Wiley & Sons, Ltd.
Surface‐sensitive Raman microscopy with total internal reflection illumination
Authors: Michaels Chris A.
Published: January 2010

A Raman microscope using a total internal reflection (TIR) annular illumination geometry through a ZnSe solid immersion lens (SIL) is described. Spectra of a thin‐film sample of the transparent organic conductor poly(3,4‐ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT:PSS) on a polyethylene terephthalate (PET) substrate are presented and compared with those from a conventional confocal Raman configuration. These spectra demonstrate a significant increase in surface selectivity upon the use of TIR illumination, as the decay length of the evanescent excitation field limits the depth of sample probed in this configuration. Spectral interference from the underlying PET substrate layer is thus greatly reduced. An increase in surface selectivity is also demonstrated for spectra acquired through the SIL with uniform illumination. Raman images of a micropatterned PEDOT:PSS film acquired with TIR illumination are also reported. Enhanced lateral resolution is realized in this configuration because of the immersion effect of the SIL, and the sampling depth is limited to 150 nm by the choice of illumination geometry. This results in analysis volumes on the order of tens of femtoliters, nearly two orders of magnitude smaller than typically achieved in conventional confocal Raman microscopes. This approach yields Raman spectra and images with surface selectivity significantly greater than can be achieved in confocal Raman, and provides a valuable tool for the microanalysis of thin surface films. Published in 2010 by John Wiley & Sons, Ltd.
Knowledge strategy: Its relationship to environmental dynamism and complexity in product development
Authors: Revilla Elena , Prieto Isabel Mª , Prado Beatriz Rodriguez
Published: January 2010

Focusing on product development, this study extends the understanding of the environment‐strategy framework and investigates the relative effect of two environmental variables, dynamism and complexity, on the product development knowledge strategy. Adopting a knowledge‐based view, and assuming that the strategy's locus is knowledge creation (exploration) and knowledge application (exploitation), the study suggests that the development of a knowledge strategy is a managerial strategic choice that is related to the environment. The results of a survey on product development managers generally indicate that exploration and exploitation must be combined according to environmental factors by generating the alternative knowledge strategies of ambidexterity or punctuated equilibrium. Particularly, the study finds that in environments characterized by high levels of both dynamism and complexity product development efforts pursue and reinforce both explorative and exploitative activities through a knowledge strategy of ambidexterity. Though not perfectly supported, punctuated equilibrium seems to be a more plausible knowledge strategy in environmental contexts where either dynamism or complexity prevails. Copyright © 2010 John Wiley & Sons, Ltd.
Prolonged vastus lateralis denervation after botulinum toxin type A injection
Authors: Dunne John W , Singer Barbara J , Silbert Peter L , Singer Kevin P
Published: January 2010

Intramuscular injection of botulinum toxin (BoNT) produces reversible blockade of neuromuscular transmission. In animal experimental models, recovery begins within four weeks and is usually complete by twelve weeks. We present evidence of prolonged denervation following BoNT injection of the vastus lateralis (VL) muscle to correct quadriceps muscle imbalance in patients with chronic anterior knee pain. Needle electromyography data were obtained from 10 subjects who had received a single BoNT treatment 5 to 19 months earlier as part of a clinical trial. Insertional and spontaneous activity, recruitment, and motor unit action potentials were examined. Clear differences between the injected and non‐injected VL muscles, which correlated with the time since injection, were identified in all subjects. All 10 subjects studied with needle EMG showed evidence of persisting denervation in the BoNT‐A injected VL muscle beyond the period of neuromotor recovery expected from animal experimental studies. © 2010 Movement Disorder Society
A novel splice site mutation in the SPG7 gene causing widespread fiber damage in homozygous and heterozygous subjects
Authors: Warnecke Tobias , Duning Thomas , Schirmacher Anja , Mohammadi Siawoosh , Schwindt Wolfram , Lohmann Hubertus , Dziewas Rainer , Deppe Michael , Ringelstein E. Bernd , Young Peter
Published: January 2010

Hereditary spastic paraplegias (HSP) are genetically and clinically heterogeneous neurodegenerative disorders. The purpose of this study was to assess the genotype and phenotype in a family with a complicated form of autosomal recessive hereditary spastic paraplegia (ARHSP). Neurological and neuropsychological evaluation, neurophysiologic studies, fiberoptic endoscopic evaluation of swallowing (FEES), neuroimaging analysis including diffusion tensor imaging (DTI), and mutation analysis of SPG4 and SPG7 gene were performed. The index case (mother) was affected by an adult‐onset form of complicated ARHSP due to the homozygous splice site mutation c.1552+1 G>T in the SPG7 gene. This mutation leads to an abnormally spliced mRNA lacking exon 11. Additional clinical features were bilateral ptosis and subtle deficits in executive function. All three asymptomatic daughters carried the sequence variation c.1552+1 G>T in heterozygous state. DTI of the mother revealed disturbance of white matter (WM) integrity in the left frontal lobe, the left corticospinal tract and both sides of the brainstem. DTI of the daughters showed subtle WM alteration in the frontal corpus callosum. The novel mutation is the first splice site mutation found in the SPG7 gene. It removes part of the AAA domain of paraplegin protein, probably leading to a loss‐of‐function of the paraplegin‐AFG3L2 complex in the mitochondrial inner membrane. The pattern of WM damage in the homozygote index case may be specific for SPG7‐HSP. The detection of cerebral WM alterations in the corpus callosum of asymptomatic heterozygote carriers confirms this brain region as the most prominent and early location of fiber damage in ARHSP. © 2010 Movement Disorder Society
The effects of physical activity on psychogenic movement disorders
Authors: Dallocchio Carlo , Arbasino Carla , Klersy Catherine , Marchioni Enrico
Published: January 2010

Psychogenic movement disorders (PMD) are a diagnostic fascinating challenge in both neurologic and psychiatric setting. Many factors influence response to treatment, but few treatment strategies are available. Physical activity proves to be effective in the treatment of depression, anxiety, and other psychiatric disorders, but the effects of regular walking exercise on patients with PMD have never been investigated in a single‐blind study. Sixteen outpatients [13 women; mean age 33.0 years (range 22–51)] with primarily mild‐to‐moderate PMD completed a thrice‐weekly, 12‐weeks mild walking program. Assessments included DSM‐IV interview, the Psychogenic Movement Disorder Rating Scale (PMDRS), Beck Anxiety Inventory (BAI), Hamilton Depression Scale (HDS), V02 Max, and body mass index (BMI). Changes in total score on the PMDRS were the primary endpoint. A comparison of all measures taken at study onset and after completing the exercise program indicates statistically significant improvements. We observed a relevant improvement in 10 of 16 patients (62%). The mean difference for the primary outcome (PMDRS total) corresponded to about 70%. Compliance was good, and there were no adverse effects. This study provides preliminary evidence for regular low‐medium intensity exercise as a safe, adequate, and pleasing intervention for PMD. Furthermore, well‐designed studies appear justified to confirm these findings. © 2010 Movement Disorder Society
Pramipexole combined with levodopa improves motor function but reduces dyskinesia in MPTP‐treated common marmosets
Authors: Tayarani‐Binazir Kayhan A. , Jackson Michael J. , Rose Sarah , Olanow C. Warren , Jenner Peter
Published: January 2010

Reduced expression of dyskinesia is observed in levodopa‐primed MPTP‐treated common marmosets when dopamine agonists are used to replace levodopa. We now investigate whether a combination of the D‐2/D‐3 agonist pramipexole and levodopa also reduces dyskinesia intensity while maintaining the reversal of motor disability. Drug naïve, non‐dyskinetic MPTP‐treated common marmosets were treated daily for up to 62 days with levodopa (12.5 mg/kg plus carbidopa 12.5 mg/kg p.o. BID) or pramipexole (0.04–0.3 mg/kg BID) producing equivalent reversal of motor disability and increases in locomotor activity. Levodopa alone resulted in marked dyskinesia induction but little or no dyskinesia resulted from the administration of pramipexole. From day 36, some animals were treated with a combination of levodopa (3.125–6.25 mg/kg plus carbidopa 12.5 mg/kg p.o. BID) and pramipexole (0.1–0.2 mg/kg p.o. SID). This improved motor disability to a greater extent than occurred with levodopa alone. Importantly, while dyskinesia was greater than that produced by pramipexole alone, the combination resulted in less intense dyskinesia than produced by levodopa alone. These results suggest that pramipexole could be administered with a reduced dose of levodopa to minimize dyskinesia in Parkinson's disease while maintaining therapeutic efficacy. © 2010 Movement Disorder Society
What features improve the accuracy of the clinical diagnosis of progressive supranuclear palsy‐parkinsonism (PSP‐P)?
Authors: Williams David R , Lees Andrew J
Published: January 2010

Progressive supranuclear palsy‐parkinsonism (PSP‐P) is a primary tauopathy characterised by neurofibrillary degeneration, which is frequently mistaken for Parkinson's disease (PD), multiple system atrophy (MSA), and vascular parkinsonism (VP) at presentation. The aim of this study was to identify particular clinical features (green flags) that may be helpful in differentiating PSP‐P from these other disorders. We identified 37 patients with PSP‐P from 726 patients archived at the Queen Square Brain Bank. Using a retrospective case notes review the clinical features were compared between the PSP‐P group and Lewy body associated parkinsonism (PD, n = 444 and dementia with Lewy bodies (DLB), n = 46), MSA (n = 90), and VP (n = 19), using the χ2‐test for proportions for a two‐by‐two contingency table. The sensitivity, specificity, and positive predictive values (PPV) and negative predictive values (NPV) were calculated for individual clinical features. A specificity of >0.85 or a PPV of >0.85 were considered reliable discriminators. No clinical features were predictive of PSP‐P, but late drug induced dyskinesias (specificity 0.92, PPV 0.99), late autonomic dysfunction (specificity 0.94, PPV 0.99) and any visual hallucinations (specificity 0.94, PPV 0.99) were better in distinguishing PD and PSP‐P than predicted using operational diagnostic criteria for PD. PSP‐P shares many clinical features with PD and DLB, MSA and VP, but visual hallucinations, drug induced dyskinesias and autonomic dysfunction are very uncommon and may be helpful exclusion criteria. © 2010 Movement Disorder Society