bluuebunny/crossref_metadata_2025 huggingface dataset:
Surface‐State‐Mediated Charge‐Transfer Dynamics in CdTe/CdSe Core–Shell Quantum Dots
Authors: Rawalekar Sachin , Kaniyankandy Sreejith , Verma Sandeep , Ghosh Hirendra N.
Published: May 2011

Herein, we report the synthesis of aqueous CdTe/CdSe type‐II core–shell quantum dots (QDs) in which 3‐mercaptopropionic acid is used as the capping agent. The CdTe QDs and CdTe/CdSe core–shell QDs are characterized by X‐ray diffraction (XRD), high‐resolution transmission electron microscopy (HR‐TEM), steady‐state absorption, and emission spectroscopy. A red shift in the steady‐state absorption and emission bands is observed with increasing CdSe shell thickness over CdTe QDs. The XRD pattern indicates that the peaks are shifted to higher angles after growth of the CdSe shell on the CdTe QDs. HR‐TEM images of both CdTe and CdTe/CdSe QDs indicate that the particles are spherical, with a good shape homogeneity, and that the particle size increases by about 2 nm after shell formation. In the time‐resolved emission studies, we observe that the average emission lifetime (τav) increases to 23.5 ns for CdTe/CdSe (for the thickest shell) as compared to CdTe QDs (τav=12 ns). The twofold increment in the average emission lifetime indicates an efficient charge separation in type‐II CdTe/CdSe core–shell QDs. Transient absorption studies suggest that both the carrier cooling and the charge‐transfer dynamics are affected by the presence of traps in the CdTe QDs and CdTe/CdSe core–shell QDs. Carrier quenching experiments indicate that hole traps strongly affect the carrier cooling dynamics in CdTe/CdSe core–shell QDs.
A Randomized Controlled Trial of Mindfulness‐Based Cognitive Therapy for Treating Tinnitus
Authors: Philippot Pierre , Nef François , Clauw Lucy , de Romrée Marie , Segal Zindel
Published: May 2011

We conducted a randomized clinical trial to examine the relative effectiveness of two psychological interventions for treating tinnitus. People with tinnitus were initially offered a single session of psychoeducation about tinnitus, followed 2 months later by six weekly sessions of either mindfulness or relaxation training. Results indicated benefits from psychoeducation in reducing negative emotions, rumination and psychological difficulties of living with tinnitus. These effects were maintained or enhanced by mindfulness training that also emphasized acceptance, although they were eroded in the relaxation condition over the follow‐up. Mediating processes are discussed, and suggestions for refining clinical interventions for this population are offered. Copyright © 2011 John Wiley & Sons, Ltd.

Key Practitioner Message

The present results suggest that mindfulness training might constitute a useful addition to psychoeducation for interventions targeting the psychological consequences of tinnitus.
Metacognitive Factors in Chronic Fatigue Syndrome
Authors: Maher‐Edwards Lorraine , Fernie Bruce A. , Murphy Gabrielle , Nikcevic Ana V. , Spada Marcantonio M.
Published: May 2011

Chronic fatigue syndrome (CFS), which is characterized by fatigue and flu‐like symptoms that are not alleviated by rest, is a poorly understood condition and an often controversial diagnosis. Earlier research has indicated that general metacognitions are associated with the severity of symptoms in patients with CFS. In the current study, we aimed to determine whether specific metacognitive factors are implicated in CFS. Using the metacognitive profiling interview template we investigated the following: (1) whether patients held positive or negative metacognitions about conceptual processes; (2) what their goals with respect to engaging in these processes were; and (3) what indicated that it was appropriate to stop. We also examined attention focus when experiencing CFS symptoms, and its advantages and disadvantages. Results showed that patients endorsed positive and negative metacognitions pertaining to conceptual processes. The goals of engaging in these processes were to identify the cause of, and devise strategies to cope with, symptoms. Patients were either unable to identify a stop signal for conceptual processing or identified an improvement in fatigue‐related symptoms as representing the stop signal. Finally, patients reported that their attention focus when experiencing symptoms included distraction and monitoring of symptoms. Advantages to these strategies included symptom management, whereas disadvantages included an escalation of negative affect. The present findings provide preliminary evidence that specific metacognitive factors may be involved in CFS. Copyright © 2011 John Wiley & Sons, Ltd.

Key Practitioner Message

Metacognitive profiling that may aid assessment and conceptualisation of psychological distress in CFS.
Limitations of Disordered Carbons Obtained from Biomass as Anodes for Real Lithium‐Ion Batteries
Authors: Caballero Alvaro , Hernán Lourdes , Morales Julián
Published: May 2011

Two disordered microporous carbons were obtained from two different types of biomass residues: olive and cherry stones. The former (OS) was activated physically under steam while the latter (CS) chemically with an aqueous solution of ZnCl2. Their structural and textural properties were studied by X‐ray diffraction, scanning electron microscopy, and N2 adsorption/desorption. Although the samples possess similar textural properties (BET surface areas, micropore surfaces and volumes), the CS carbon is more disordered than the OS carbon. Their electrochemical response in half‐cells (CS [OS]/Li) is good; the values are comparable to those obtained from mesocarbon microbeads commonly used in commercial lithium‐ion batteries, which consist of highly graphitized carbon. However, cells featuring the OS or CS carbon as anode and LiMn2O4 as cathode perform poorly. Electrochemical activation of the electrodes against lithium metal, a recommended procedure for boosting the electrochemical properties of real lithium‐ion batteries, improves cell performance (particularly with OS) but is ultimately ineffective: the delivered average capacity of the activated cell made from OS was less than half its theoretical value. The high irreversible capacity, high polarization between the charge and discharge curves, combined with the presence of various functional groups and the high disorder of the studied carbons which may facilitate side reactions such as electrolyte decomposition, results in a degraded cell performance.
Behavioral screening for neuroactive drugs in zebrafish
Authors: Rihel Jason , Schier Alexander F.
Published: May 2011

The larval zebrafish has emerged as a vertebrate model system amenable to small molecule screens for probing diverse biological pathways. Two large‐scale small molecule screens examined the effects of thousands of drugs on larval zebrafish sleep/wake and photomotor response behaviors. Both screens identified hundreds of molecules that altered zebrafish behavior in distinct ways. The behavioral profiles induced by these small molecules enabled the clustering of compounds according to shared phenotypes. This approach identified regulators of sleep/wake behavior and revealed the biological targets for poorly characterized compounds. Behavioral screening for neuroactive small molecules in zebrafish is an attractive complement to in vitro screening efforts, because the complex interactions in the vertebrate brain can only be revealed in vivo. © 2011 Wiley Periodicals, Inc. Develop Neurobiol 72: 373–385, 2012
Synaptic defects in spinal muscular atrophy animal models
Authors: Torres‐Benito Laura , Ruiz Rocío , Tabares Lucía
Published: May 2011

Proximal spinal muscular atrophy, the most frequent genetic cause of childhood lethality, is caused by homozygous loss or mutation of the SMN1 gene on human chromosome 5, which codes for the survival motor neuron (SMN) protein. SMN plays a role in the assembly of small nuclear ribonucleoproteins and, additionally, in synaptic function. SMN deficiency produces defects in motor neuron β‐actin mRNA axonal transport, neurofilament dynamics, neurotransmitter release, and synapse maturation. The underlying molecular mechanisms and, in particular, the role of the cytoskeleton on the pathogenesis of this disease are starting to be revealed. © 2011 Wiley Periodicals, Inc. Develop Neurobiol 72: 126–133, 2012
Optogenetics: A new enlightenment age for zebrafish neurobiology
Authors: Del Bene Filippo , Wyart Claire
Published: May 2011

Zebrafish became a model of choice for neurobiology because of the transparency of its brain and because of its amenability to genetic manipulation. In particular, at early stages of development the intact larva is an ideal system to apply optical techniques for deep imaging in the nervous system, as well as genetically encoded tools for targeting subsets of neurons and monitoring and manipulating their activity. For these applications, new genetically encoded optical tools, fluorescent sensors, and light‐gated channels have been generated, creating the field of “optogenetics.” It is now possible to monitor and control neuronal activity with minimal perturbation and unprecedented spatio‐temporal resolution. We describe here the main achievements that have occurred in the last decade in imaging and manipulating neuronal activity in intact zebrafish larvae. We provide also examples of functional dissection of neuronal circuits achieved with the applications of these techniques in the visual and locomotor systems. © 2011 Wiley Periodicals, Inc. Develop Neurobiol 72: 404–414, 2012
CD40 translocation to lipid rafts: Signaling requirements and downstream biological events
Authors: Nadiri Amal , Polyak Maria J. , Jundi Malek , Alturaihi Haydar , Reyes‐Moreno Carlos , Hassan Ghada S. , Mourad Walid
Published: May 2011

CD40, a member of the TNF receptor family, is expressed on a variety of immune and non‐immune cells. Its interaction with its ligand, CD154, plays a pivotal role in humoral and cell‐mediated immunity. A low level of CD40 is constitutively associated within membrane lipid rafts and, upon engagement, this level is significantly enhanced. In this study, our objective is to evaluate the process of CD40/lipid raft association in terms of the signals required for its initiation and the resulting biological outcomes. Here, we show the CD40/lipid raft association to be independent of PI‐3‐kinase, Src family kinases and p38 MAPK pathways. Moreover, CD40 lacking its intracellular domain, which is usually required for CD40‐mediated signaling, still localizes to lipid rafts upon engagement, confirming that the CD40/lipid raft association is independent of signaling events. As to the biological outcomes of the CD40/lipid raft association, we show that disrupting lipid raft integrity selectively abolishes CD40‐mediated Akt phosphorylation. In addition, replacing the transmembrane domain of CD40 with that of CD45 (a protein excluded from lipid rafts) dramatically reduced CD40‐mediated Akt phosphorylation and B7.1 upregulation, while not influencing p38, ERK and JNK activation. Together, these findings clarify the requirements for CD40/lipid raft association and the signals triggered upon CD40 engagement by CD154.
The Rubrenic Synthesis: The Delicate Equilibrium between Tetracene and Cyclobutene
Authors: Braga Daniele , Jaafari Abdelhafid , Miozzo Luciano , Moret Massimo , Rizzato Silvia , Papagni Antonio , Yassar Abderrahim
Published: May 2011

Herein we describe the synthesis of new substituted tetraaryltetracenes, obtained by the dimerization of triarylchloroallenes, prepared from propargyl alcohols. The propargyl alcohols were prepared by two different synthetic strategies and then the alcohols were treated to obtain the corresponding acenes. In addition to the expected tetracene derivatives, we observed the formation of bis(alkylidene)cyclobutenes. When strong electron‐donating substituents were present, the main product was the cyclobutene. We discuss a reaction mechanism that accounts for the formation of the cyclobutenes.
Efficient Asymmetric Synthesis of Long‐Chain Polyketides Containing up to Ten Contiguous Stereogenic Centres by Double Chain Elongation
Authors: Turks Maris , Fairweather Kelly A. , Scopelliti Rosario , Vogel Pierre
Published: May 2011

The 2,3‐anti‐3,4‐syn‐stereotriad (1Z,2S,3R,4S)‐1‐ethylidene‐2,4‐dimethyl‐3‐[(1S)‐1‐phenylethoxy]‐5‐oxopent‐1‐yl isobutyrate {(–)‐8, obtained in a one‐pot operation from the trimethylsilyl (Z)‐enol ether derived from pentan‐3‐one and(1E,3Z)‐1[(1S)‐phenylethoxy]‐2‐methylpenta‐1,3‐dien‐3‐ylisobutyrate through SO2 umpolung} contains an ethyl ketone moiety that undergoes diastereoselective cross‐aldol reactions with acetaldehyde. After subsequent reductions, various diastereomeric stereohexads (polypropionate fragments containing six contiguous stereogenic centres) in which the (Z)‐enol isobutyrate units remained intact were obtained. After suitable protection, these were converted into their corresponding lithium (Z)‐enolates, which could react with isopropylidene D‐glyceraldehyde [(+)‐9] to give aldol products that were reduced to various stereodecads (polyketides with ten contiguous stereogenic centres). The disclosed chemistry represents a quick, asymmetric, diastereoselective andstereodivergent construction of long‐chain polyketides and analogues by a double‐chain‐elongation strategy.
Experimental and Theoretical Investigation of Hydrogenative Cyclization of Allenynes
Authors: Kim Hyo‐Tong , Yoon Hyo‐Sang , Jang Woo‐Young , Kang Youn K. , Jang Hye‐Young
Published: May 2011

Upon platinum‐catalyzed hydrogenation, allenynes underwent reductive cyclization to provide hetero‐ and carbocycles with completely controlled regio‐ and stereoselectivity. By employing hydrogen as a reductant, the use of stoichiometric amounts of toxic organometallic reductants was avoided, leading to clean and cost‐effective synthesis. A possible catalytic cycle is proposed on the basis of a deuterium‐labeling study and theoretical calculations.
Direct Electrooxidation of Ascorbic Acid at the Nanocrystaline Graphite‐like Pyrolytic Carbon Film Electrode
Authors: Hadi M. , Rouhollahi A. , Yousefi M.
Published: May 2011

Pyrolytic carbon films (PCFs) were prepared by chemical vapor deposition (CVD) at different deposition temperatures. As an example of using PCF electrode in electroanalysis, the direct electrooxidation of ascorbic acid (AA) at the PCF electrode was investigated and compared with common carbon‐based electrodes such as glassy carbon (GC), edge plane pyrolytic graphite (EPPG), and basal plane pyrolytic graphite (BPPG) electrodes. It was found that the PCF electrodes prepared under deposition temperatures higher than 1050 °C showed a higher sensitivity and lower overpotential compared to the other carbon electrodes. The electrode was successfully applied for determination of AA in real samples.
Diffusion spectral imaging modules correlate with EEG LORETA neuroimaging modules
Authors: Thatcher Robert W. , North Duane M. , Biver Carl J.
Published: May 2011

Objectives: The purpose of this study was to test the hypothesis that the highest temporal correlations between 3‐dimensional EEG current source density corresponds to anatomical Modules of high synaptic connectivity. Methods: Eyes closed and eyes open EEG was recorded from 19 scalp locations with a linked ears reference from 71 subjects age 13–42 years. LORETA was computed from 1 to 30 Hz in 2,394 cortical gray matter voxels that were grouped into six anatomical Modules corresponding to the ROIs in the Hagmann et al.'s [2008] diffusion spectral imaging (DSI) study. All possible cross‐correlations between voxels within a DSI Module were compared with the correlations between Modules. Results: The Hagmann et al. [ 2008] Module correlation structure was replicated in the correlation structure of EEG three‐dimensional current source density. Conclusions: EEG Temporal correlation between brain regions is related to synaptic density as measured by diffusion spectral imaging. Hum Brain Mapp, 2011. © 2011 Wiley‐Liss, Inc.
Optimal design for nonlinear estimation of the hemodynamic response function
Authors: Maus Bärbel , van Breukelen Gerard J. P. , Goebel Rainer , Berger Martijn P. F.
Published: May 2011

Subject‐specific hemodynamic response functions (HRFs) have been recommended to capture variation in the form of the hemodynamic response between subjects (Aguirre et al., [1998]: Neuroimage 8:360–369). The purpose of this article is to find optimal designs for estimation of subject‐specific parameters for the double gamma HRF. As the double gamma function is a nonlinear function of its parameters, optimal design theory for nonlinear models is employed in this article. The double gamma function is linearized by a Taylor approximation and the maximin criterion is used to handle dependency of theD‐optimal design on the expansion point of the Taylor approximation. A realistic range of double gamma HRF parameters is used for the expansion point of the Taylor approximation. Furthermore, a genetic algorithm (GA) (Kao et al., [2009]: Neuroimage 44:849–856) is applied to find locally optimal designs for the different expansion points and the maximin design chosen from the locally optimal designs is compared to maximin designs obtained bym‐sequences, blocked designs, designs with constant interstimulus interval (ISI) and random event‐related designs. The maximin design obtained by the GA is most efficient. Random event‐related designs chosen from several generated designs andm‐sequences have a high efficiency, while blocked designs and designs with a constant ISI have a low efficiency compared to the maximin GA design. Hum Brain Mapp, 2011. © 2011 Wiley‐Liss, Inc.
Self‐face recognition in social context
Authors: Sugiura Motoaki , Sassa Yuko , Jeong Hyeonjeong , Wakusawa Keisuke , Horie Kaoru , Sato Shigeru , Kawashima Ryuta
Published: May 2011

The concept of “social self” is often described as a representation of the self‐reflected in the eyes or minds of others. Although the appearance of one's own face has substantial social significance for humans, neuroimaging studies have failed to link self‐face recognition and the likely neural substrate of the social self, the medial prefrontal cortex (MPFC). We assumed that the social self is recruited during self‐face recognition under a rich social context where multiple other faces are available for comparison of social values. Using functional magnetic resonance imaging (fMRI), we examined the modulation of neural responses to the faces of the self and of a close friend in a social context. We identified an enhanced response in the ventral MPFC and right occipitoparietal sulcus in the social context specifically for the self‐face. Neural response in the right lateral parietal and inferior temporal cortices, previously claimed as self‐face‐specific, was unaffected for the self‐face but unexpectedly enhanced for the friend's face in the social context. Self‐face‐specific activation in the pars triangularis of the inferior frontal gyrus, and self‐face‐specific reduction of activation in the left middle temporal gyrus and the right supramarginal gyrus, replicating a previous finding, were not subject to such modulation. Our results thus demonstrated the recruitment of a social self during self‐face recognition in the social context. At least three brain networks for self‐face‐specific activation may be dissociated by different patterns of response‐modulation in the social context, suggesting multiple dynamic self‐other representations in the human brain. Hum Brain Mapp, 2011. © 2011 Wiley‐Liss, Inc.
Entecavir treatment for chronic hepatitis B: Adaptation is not needed for the majority of naïve patients with a partial virological response
Authors: Zoutendijk Roeland , Reijnders Jurriën G. P. , Brown Ashley , Zoulim Fabien , Mutimer David , Deterding Katja , Petersen Jörg , Peter Hofmann Wolf , Buti Maria , Santantonio Teresa , van Bömmel Florian , Pradat Pierre , Oo Ye , Luetgehetmann Marc , Berg Thomas , Hansen Bettina E. , Wedemeyer Heiner , Janssen Harry L. A.
Published: May 2011

Entecavir (ETV) is a potent inhibitor of viral replication in nucleos(t)ide analogue (NA)-naïve chronic hepatitis B (CHB) patients. The aim of this study was to investigate the long term efficacy and safety of ETV in NA-naïve CHB patients, particularly in those with detectable hepatitis B virus (HBV) DNA after 48 weeks, in whom treatment adaptation is suggested by current guidelines. In a multicenter cohort study, we investigated 333 CHB patients treated with entecavir monotherapy. The NA-naïve population consisted of 243 patients, whereas 90 were NA-experienced. Virological response (VR) (HBV DNA <80 IU/mL) was achieved in 48%, 76%, and 90% of hepatitis B e antigen (HBeAg)-positive and in 89%, 98%, and 99% of HBeAg-negative NA-naïve patients at weeks 48, 96, and 144, respectively. Thirty-six of 175 (21%) NA-naïve patients with at least 48 weeks of follow-up had a detectable load at week 48 (partial virological response [PVR]). Twenty-nine (81%) patients with PVR reached VR during prolonged ETV monotherapy, and none of them developed ETV-resistance. Among 22 patients with HBV DNA <1,000 IU/mL at week 48, VR was achieved in 21 (95%) patients, compared with eight of 14 (57%) patients with HBV DNA ≥1,000 IU/mL. Continuous HBV DNA decline was observed in most patients without VR during follow-up, and in three patients adherence was suboptimal according to the treating physician. ETV was safe and did not affect renal function or cause lactic acidosis.

Conclusion:

ETV monotherapy can be continued in NA-naïve patients with detectable HBV DNA at week 48, particularly in those with a low viral load because long-term ETV leads to a virological response in the vast majority of patients. (Hepatology 2011;)
Carcinogen-induced hepatic tumors in KLF6+/− mice recapitulate aggressive human hepatocellular carcinoma associated with p53 pathway deregulation
Authors: Tarocchi Mirko , Hannivoort Rebekka , Hoshida Yujin , Lee Ursula E. , Vetter Diana , Narla Goutham , Villanueva Augusto , Oren Moshe , Llovet Josep M. , Friedman Scott L.
Published: May 2011

Inactivation of KLF6 is common in hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) infection, thereby abrogating its normal antiproliferative activity in liver cells. The aim of the study was to evaluate the impact of KLF6 depletion on human HCC and experimental hepatocarcinogenesis

in vivo
. In patients with surgically resected HCC, reduced tumor expression of KLF6 was associated with decreased survival. Consistent with its role as a tumor suppressor, KLF6+/− mice developed significantly more tumors in response to the chemical carcinogen diethyl nitrosamine (DEN) than wild-type animals. Gene expression signatures in both surrounding tissue and tumors of KLF6+/− mice closely recapitulated those associated with aggressive human HCCs. Expression microarray profiling also revealed an increase in

Mdm2

mRNA in tumors from KLF6+/− compared with KLF6+/+ mice, which was validated by way of quantitative real-time polymerase chain reaction and western blot analysis in both human HCC and DEN-induced murine tumors. Moreover, chromatin immunoprecipitation and cotransfection assays established the P2 intronic promoter of

Mdm2

as a

bona fide

transcriptional target repressed by KLF6. Whereas KLF6 overexpression in HCC cell lines and primary hepatocytes led to reduced MDM2 levels and increased p53 protein and transcriptional activity, reduction in KLF6 by small interfering RNA led to increased MDM2 and reduced p53.

Conclusion:

Our findings indicate that KLF6 deficiency contributes significantly to the carcinogenic milieu in human and murine HCC and uncover a novel tumor suppressor activity of KLF6 in HCC by linking its transcriptional repression of

Mdm2

to stabilizing p53. (Hepatology 2011;)
Human leukocyte antigen in primary biliary cirrhosis: An old story now reviving
Authors: Invernizzi Pietro
Published: May 2011

Primary biliary cirrhosis (PBC) is an autoimmune biliary disease characterized by injury of small and medium size bile ducts, eventually leading to liver cirrhosis and death. Although the causes remain enigmatic, recent evidence has strengthened the importance of genetic factors in determining the susceptibility to the disease. Besides the strong heritability suggested by familial occurrence and monozygotic twins concordance, for decades there has not been a clear association with specific genes, with the only exception of a low risk conferred by a class II human leukocyte antigen (HLA) variant, the DRB1*08 allele, at least in some populations. The picture has become more complete when strong protective associations between PBC and the HLA DRB1*11 and DRB1*13 alleles were found in Italian and UK series. However, HLA genes have begun again to attract interest thanks to recent genome-wide association studies (GWAS), which clearly demonstrated that the major components of the genetic architecture of PBC are within the HLA region. As expected in a genetically complex disease, GWAS also identified several novel non-HLA variants, but it is worth noting that all of them are in immuno-related genes. In this review, the paradigmatic tale of what, and how, we learned about HLA genes in PBC will be retraced with particular focus on how GWAS are enabling a rewriting the story of PBC pathogenesis. These recent discoveries will not only drive functional studies but will also hold the promise of developing novel disease-specific treatments. (Hepatology 2011;)
Aryl hydrocarbon receptor‐mediated impairment of chondrogenesis and fracture healing by cigarette smoke and benzo(α)pyrene
Authors: Kung Ming H. , Yukata Kiminori , O'Keefe Regis J. , Zuscik Michael J.
Published: May 2011

The clinical literature strongly suggests that bone healing in cigarette smokers is impaired. Since cigarette smoke (CS) contains numerous polycyclic aromatic hydrocarbons (PAHs), and since dioxins impair bone formation in vivo via the Aryl Hydrocarbon Receptor (AHR), we investigated the impact of PAH/AHR signaling on chondrogenesis and on healing in a mouse tibial fracture model. We established that CS activates AHR signaling in fractures by up‐regulating the AHR target gene cytochrome p4501A1 (Cyp1A1). For in vitro studies, we employed the mouse limb bud micromass chondrogenesis model. After confirming that chondrocytes express AHR during differentiation, we treated cells with a prototypical PAH found in CS, benzo(α)pyrene (BaP), or cigarette smoke extract (CSE). Both BaP and CSE strongly inhibited chondrogenesis in mesenchymal cells generated from E11 limb buds, with BaP also accelerating chondrocyte hypertrophy in cultures generated from E12 limb buds. Detection of DNA adducts in the BaP‐treated cultures suggests that the distinct phenotypic effects of BaP may be due to the formation of reactive metabolites. Blockade of AHR signaling with the AHR antagonist MNF reverses the effects of BaP, but not CSE, suggesting that CSE inhibition of chondrogenesis is AHR‐independent. Correlating with these results, tibial fracture calluses from BaP‐treated mice were smaller and contained less mineralized tissue than vehicle controls. Overall, BaP is identified as a potent inhibitor of chondrogenesis in vitro with correlated effects on fracture healing similar to those of CS itself, suggesting a basis for PAHs as key compounds in the influence of CS on fracture repair. J. Cell. Physiol. 227: 1062–1070, 2012. © 2011 Wiley Periodicals, Inc.
Phosphorylation of the gastric tumor suppressor RUNX3 following H. pylori infection results in its localization to the cytoplasm
Authors: Cinghu Senthilkumar , Goh Yun‐Mi , Oh Byung‐Chul , Lee You‐Soub , Lee Ok‐Jun , Devaraj Halagowder , Bae Suk‐Chul
Published: May 2011

As H. pylori infection progresses, intestinal metaplasia (IM), a key event in gastric carcinogenesis, develops in the stomach. The mechanism by which H. pylori infection causes the trans‐differentiation of gastric cells to intestinal‐type cells remains an important question. In the current study, we found that RUNX3 is deregulated in all human IM specimens examined by either down regulation or mislocalization; Aberrant localization of a gastric tumor suppressor RUNX3 is observed in most human cases of IM with concurrent H. pylori infection, and RUNX3 is down‐regulated in most cases of IM without H. pylori‐infection. The cytoplasmic mislocalization of a RUNX3 was associated with H. pylori‐induced c‐Src activation and RUNX tyrosine phosphorylation. Moreover, gastric epithelial cells of Runx3−/− mice expressed the intestinal markers Muc2 and Li‐Cadherin, which suggests that the deregulation of Runx3 is a key event in the intestinalization of the gastric epithelium. Collectively, the results of the current study suggest that RUNX3 deregulation is associated with H. pylori‐induced pathogenesis and the development of IM. J. Cell. Physiol. 227: 1071–1080, 2012. © 2011 Wiley Periodicals, Inc.
TWEAK causes myotube atrophy through coordinated activation of ubiquitin‐proteasome system, autophagy, and caspases
Authors: Bhatnagar Shephali , Mittal Ashwani , Gupta Sanjay K. , Kumar Ashok
Published: May 2011

Proinflammatory cytokine TWEAK has now emerged as a key mediator of skeletal muscle‐wasting in many catabolic conditions. However, the mechanisms by which TWEAK induces muscle proteolysis remain poorly understood. Here, we have investigated the role of ubiquitin‐proteasome system, autophagy, and caspases in TWEAK‐induced muscle wasting. Addition of TWEAK to C2C12 myotubes stimulated the ubiquitination of myosin heavy chain (MyHC) and augmented the expression of E3 ubiquitin ligase MuRF1. Pretreatment of myotubes with proteasome inhibitors MG132 or lactacystin or knockdown of MuRF1 by RNAi blocked the TWEAK‐induced degradation of MyHC and myotube atrophy. TWEAK increased the expression of several autophagy‐related molecules. Moreover, the inhibitors of autophagy improved the levels of MyHC in TWEAK‐treated myotubes. TWEAK also increased activity of caspases in C2C12 myotubes. Pan‐caspase or caspase 3 inhibitory peptide inhibited the TWEAK‐induced loss of MyHC and myotube diameter. Our study demonstrates that nuclear factor‐kappa B (NF‐κB) transcription factor is essential for TWEAK‐induced expression of MuRF1 and Beclin1. Furthermore, our results suggest that caspases contribute, at least in part, to the activation of NF‐κB in response to TWEAK treatment. Collectively, the present study provides novel insight into the mechanisms of action of TWEAK in skeletal muscle. J. Cell. Physiol. 227: 1042–1051, 2012. © 2011 Wiley Periodicals, Inc.
Induction of Paneth cell degranulation by orally administered Toll‐like receptor ligands
Authors: Rumio Cristiano , Sommariva Michele , Sfondrini Lucia , Palazzo Marco , Morelli Daniele , Viganò Laura , De Cecco Loris , Tagliabue Elda , Balsari Andrea
Published: May 2011

The secretory activity of Paneth cells is related to the bacterial milieu in the small intestine; however, the molecules involved in inducing Paneth cell secretion of enzymes and antimicrobial peptides are not well‐defined. Mice treated orally with CpG‐oligodeoxynucleotide (ODN), an agonist of Toll‐like receptor (TLR) 9, showed rapid and massive Paneth cell degranulation. CpG‐ODN‐induced degranulation was not observed in TLR9−/− mice or in chimeric TLR9−/− mice reconstituted with wild‐type (WT) bone marrow, but was observed in WT mice reconstituted with TLR9−/− bone marrow, indicating a role for TLR9‐expressing gastrointestinal cells in CpG recognition. The TLR3 agonist polyinosinic‐polycytidylic acid also induced rapid degranulation, whereas the TLR4 and TLR5 agonists LPS and flagellin, respectively, induced late degranulation mediated by TNF‐α. Our evidence that TLR9 and TLR3 agonists induce Paneth cell degranulation points to the need for further studies of the mechanisms underlying Paneth cell function as an avenue toward preventing infection and treating inflammatory bowel diseases. J. Cell. Physiol. 227: 1107–1113, 2012. © 2011 Wiley Periodicals, Inc.
Latexin regulates the abundance of multiple cellular proteins in hematopoietic stem cells
Authors: Mitsunaga Kanae , Kikuchi Jiro , Wada Taeko , Furukawa Yusuke
Published: May 2011

Latexin is the only known carboxypeptidase A inhibitor in mammals and shares structural similarity with cystatin C, suggesting that latexin regulates the abundance of as yet unidentified target proteins. A forward genetic approach revealed that latexin is involved in homeostasis of hematopoietic stem cells (HSCs) in mice; however, little is known about the mechanisms by which latexin negatively affects the numbers of HSCs. In this study, we found that latexin is preferentially expressed in hematopoietic stem/progenitor cells, and is co‐localized with the molecules responsible for the interaction of HSCs with a bone marrow niche, such as N‐cadherin, Tie2, and Roundabout 4. Latexin‐knockout young female mice showed an increase in the numbers of KSL (c‐Kit+/Sca‐1+/linegae marker‐negative) cells, which may be attributable to enhanced self‐renewal because latexin‐deficient KSL cells formed more colonies than their wild‐type counterparts in methylcellulose culture. Proteomic analysis of Sca‐1+ bone marrow cells demonstrated that latexin ablation reduced the abundance of multiple cellular proteins, including N‐cadherin, Tie2, and Roundabout 4. Finally, we found that latexin expression was lost or greatly reduced in approximately 50% of human leukemia/lymphoma cell lines. These results imply that latexin inhibits the self‐renewal of HSCs by facilitating the lodgment of HSCs within a bone marrow niche to maintain HSC homeostasis. J. Cell. Physiol. 227: 1138–1147, 2012. © 2011 Wiley Periodicals, Inc.
Characterization of a p‐nitrophenol‐degrading mixed culture with an improved methodology of fluorescence in situ hybridization and confocal laser scanning microscopy
Authors: Suárez‐Ojeda María Eugenia , Montón Helena , Roldán Mónica , Martín‐Hernández Mariángel , Pérez Julio , Carrera Julián
Published: May 2011

BACKGROUND: Confocal laser scanning microscopy (CLSM) provides critical information of the presence of autofluorescence signals inherent to the samples under study, which may interfere with probe fluorescence. Therefore, it is important to determine the emission spectrum of the biomass autofluorescence under study in order to avoid, as much as possible, this wavelength range when selecting specific probe emissions and to modify, if necessary, the original fluorescence in situ hybridization (FISH) protocol in order to enhance probes signals.

RESULTS: Microbial characterization of a p‐nitrophenol‐degrading activated sludge through a conventional FISH protocol was not possible because the fluorescence signal of the unlabelled cells was similar to or even higher than the signal emitted by hybridized cells, impeding the separation of the two signals and therefore, preventing biomass characterization. An optimized but simple FISH approach was developed in order to ease observation of the p‐nitrophenol‐degrading bacteria studied in this work. The final results allowed identification of Arthrobacter sp. (Micrococcaceae family) and genus Acinetobacter (Moraxellaceae family) in the p‐nitrophenol‐degrading activated sludge, whereas no hybridization was found for Pseudomonas spp.

CONCLUSIONS: The hypothesis of a mixed culture following, at the same time, different degradation pathways has been confirmed through the microbial characterization of enriched p‐nitrophenol‐degrading activated sludge. Copyright © 2011 Society of Chemical Industry
Particle size distribution based evaluation of biodegradation and treatability for leachate from organic waste
Authors: Doǧruel Serdar , Köktuna Merve , Çokgör Emine Ubay , Sözen Seval , Orhon Derin
Published: May 2011

BACKGROUND: The study evaluated the relationship between particle size distribution (PSD) of chemical oxygen demand (COD) and treatability of leachate generated by organic waste. PSD determinations were performed together with physico‐chemical and biological treatability studies. Leachate biodegradation was also evaluated by means of oxygen uptake rate (OUR) profiles and experimental results were used for calibration of the adopted mathematical model.

RESULTS: The leachate was characterized by a COD content of 80 000 mg L−1 in summer. PSD analysis showed a bimodal distribution with around 60% of the COD below 2 nm and 25% above 1600 nm. Chemical treatment by lime and alum provided limited COD removal (30‐35%). The extent of COD removal was higher than the particulate COD fraction above 1600 nm, it also occurred in the soluble range below 2 nm through adsorption. A modeling study indicated three major COD fractions that could be correlated with PSD analysis: readily biodegradable COD and slowly biodegradable COD in the soluble range and hydrolyzable COD fraction in the particulate range.

CONCLUSION: PSD‐based COD fractionation adequately explained limitations of chemical treatment efficiency; it was also a reliable complement to the currently used respirometric tests for biodegradation, providing insight to the fate of different COD fractions included in the soluble range (<2 nm) and yielding concrete supporting information on the generation of soluble residual microbial products. Copyright © 2011 Society of Chemical Industry
Programmed neuronal cell death induced by HIV‐1 tat and methamphetamine
Authors: Qi Li , Gang Lu , Hang Kwong Wing , Ling Choi Heung , Xiaofeng Zeng , Zhen Li , David Wai YEW , Sang Poon Wai
Published: May 2011

Apoptosis and autophagy are the two major types of programmed cell death (PCD) in neurons. Homeostatic autophagy often precedes apoptosis, and when apoptosis is blocked, the failure to keep homeostasis will lead to necrosis instead. It has been reported that human immunodeficiency virus (HIV) infected methamphetamine (Meth) abusers represent greater neuropathological abnormalities than Meth abusers or HIV‐positive non‐Meth users. Recent publications suggest that Tat and Meth when administered together result in greater neuronal damage than when administered separately. However, the cellular events of the combined Tat‐Meth effect have not yet been fully characterized. Therefore, we investigated the effects of Tat and/or Meth on apoptosis and autophagy to elucidate whether PCD was involved in Tat and/or Meth‐induced neuronal damage. Annexin‐V‐FITC/PI staining assay was used to detect cellular apoptosis using a neuroblastoma cell line SH‐SY5Y. Cellular ultrastructural changes were observed under transmission electron microscopy (TEM). Flow‐cytometric data showed apoptosis following Meth treatment, and more extensive apoptosis with Tat + Meth treatment. The most important finding was that the autophagosome and/or multilamellar bodies (MLBs) were most pronounced with Tat + Meth treatment, were less so with Meth treatment, and infrequent with Tat treatment. This suggests the involvement of autophagy and apoptosis in Tat with Meth‐elicited cell damage. However, the relation between apoptosis and autophagy remains unknown in this experiment. Further research is needed to analyze the relation among related molecules. A thorough understanding of this multifaceted relationship will be critical for the assessment of therapeutic modalities for patients with HIV with drug abuse. Microsc. Res. Tech., 2011. © 2011 Wiley Periodicals, Inc.
Zinc as an essential trace element in the acceleration of matrix vesicles‐mediated mineral deposition
Authors: Kawakubo Atsushi , Matsunaga Tsunenori , Ishizaki Hidetaka , Yamada Shizuka , Hayashi Yoshihiko
Published: May 2011

BACKGROUND: Zinc (Zn) has a potent stimulatory effect on osteoblastic bone formation and an inhibitory effect on osteoclastic bone resorption. PURPOSE: The effect of Zn on the function of matrix vesicles (MVs) remains controversial. The purpose of this study was to investigate the effect of Zn on alkaline phosphatase (ALP) activity of osteoblasts and in the initial biological MVs‐mediated mineral deposition. STUDY DESIGN: Osteoblasts were treated with varying concentrations of Zn dissolved in culture medium. After three, five, and seven days of culture, ALP activity was assayed. For the detection of a low level of calcium concentration in MVs, X‐ray fluorescence (XRF) analyses were applied. The effect of Zn for the transformation of calcium phosphate was analyzed using a scanning electron microscope fitted with an energy dispersive X‐ray microanalysis (EDX) system. RESULTS: The ALP activity of osteoblasts in culture medium supplemented with 1 × 10−5M of Zn was significantly increased at both five and seven days. XRF data demonstrated higher levels of calcium concentration over time in the Zn‐supplemented group. EDX data showed that mineral deposits beginning on day 3 were transformed from whitlockite to calcium phosphate near hydroxyapatite, and that Zn accelerated this transformation. CONCLUSIONS: The proper concentration of Zn increased the ALP activity of osteoblasts after five and seven days of incubation. The present XRF and EDX data suggest that the increase of mineral deposition with Zn exposure for one to five days might be mediated by the activation of ALP and calcium‐binding proteins. Microsc. Res. Tech., 2011. © 2011 Wiley Periodicals, Inc.
WHY DO FIRMS PAY BRIBES? FIRM‐LEVEL EVIDENCE FROM THE CAMBODIAN GARMENT INDUSTRY
Authors: Kasuga Hidefumi
Published: May 2011

This paper investigates the causes and effects of bribe payments using data from garment‐producing firms in Cambodia. We uncover the reasons why firms pay bribes and describe what they receive in return. We test the hypothesis that bribe payments reduce bureaucratic delays and find that bribery can improve productivity by reducing bureaucratic delays. The evidence suggests that, if the government improves administrative services, firms can reduce unofficial payments because unavoidable bureaucratic delays compel them to pay bribes. Our evidence also suggests that foreign ownership can explain why firms are not harassed heavily in this industry. Copyright © 2011 John Wiley & Sons, Ltd.
Effect of antiviral therapy on the immunohistochemical expression of bcl‐xL and bax protein in patients with HBeAg‐negative chronic hepatitis B
Authors: Cholongitas Evangelos , Papatheodoridis George V. , Manesis Emanuel K. , Petraki Kaliopi , Tiniakos Dina , Hadziyannis Stephanos J.
Published: May 2011

The effect of antiviral treatment on apoptosis in chronic hepatitis B (CHB) has not been clarified. We evaluated the hepatic immunohistochemical expression of the pro‐apoptotic bax and the antiapoptotic bcl‐xL protein in HBeAg‐negative CHB patients before and after treatment. In our study we included 72 paired biopsies from 36 HBeAg‐negative CHB patients: 29 treated (interferon‐alfa: 17, adefovir: 12) and 7 untreated. Changes in expression of apoptotic proteins (D‐bax, D‐bcl‐xL), necroinflammation and fibrosis (D‐grade/D‐stage) (Ishak classification) were evaluated. We found that Bax‐positive compared to bax‐negative biopsies had worse necroinflammation (8.2 vs. 6.7, P = 0.05) and fibrosis score (3.9 vs. 3, P = 0.036). bcl‐xL‐positive compared to bcl‐xL‐negative biopsies had lower intralobular inflammation (1.6 vs. 2.2, P = 0.03). Decreased compared to stable/increased D‐bax was associated with greater improvement in necroinflammation only in treated patients (D‐grade: −4.6 vs. −1.6, P = 0.05) and greater fibrosis improvement in interferon treated patients (D‐stage: −0.4 vs. 0.55, P = 0.05). Increased compared to stable/decreased total apoptotic trend [D‐apoptosis: (D‐bax)‐(D‐bcl‐xL)], was associated with worsening fibrosis, particularly in adefovir treated patients (D‐stage: 2.3 vs. 0, P = 0.004). In the 11 patients without significant changes from 1st to 2nd biopsy, increased apoptosis was more frequent in treated than untreated cases (P = 0.046). In multivariate analysis, bax change was independently associated with change of grade (P = 0.038) and antiviral therapy (P = 0.015). In conclusions, in HBeAg‐negative CHB, histological improvement after treatment is associated with decreased hepatocyte apoptosis. In patients without substantial histological changes, treatment seems to increase the apoptosis of hepatocytes, thus having a possible protective effect on hepatocarcinogenesis. J. Med. Virol. 83:1165–1171, 2011. © 2011 Wiley‐Liss, Inc.
Human T cell lymphotropic virus type 1 (HTLV‐1) proviral load of HTLV‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients according to new diagnostic criteria of HAM/TSP
Authors: Grassi Maria Fernanda Rios , Olavarria Viviana Nilla , Kruschewsky Ramon de Almeida , Mascarenhas Rita Elizabeth , Dourado Inês , Correia Luis C.L. , de Castro‐Costa Carlos Maurício , Galvão‐Castro Bernardo
Published: May 2011

A high human T‐cell lymphotropic virus type 1 (HTLV‐1) proviral load is described in HTLV‐1‐associated diseases, especially HAM/TSP. However, the cut‐off value to define high levels of HTLV‐1 proviral load is not well established. 281 HTLV‐1‐infected patients from the HTLV reference center in Salvador, Brazil, were followed from 2005 to 2008. Patients were classified as asymptomatic, possible‐, probable‐, and definite‐HAM/TSP, in accordance with diagnostic criteria proposed by De Castro‐Costa et al. (2006): AIDS Res Hum Retroviruses 22:931–935. HTLV‐1 proviral load was determined using real‐time PCR. A receiver operator characteristic (ROC) curve was constructed using only asymptomatic individuals and definite‐HAM/TSP patients. The ROC curve was used to predict the proviral load level that differentiates these two groups. Out of 281 patients, 189 were asymptomatic and 92 were diagnosed with HAM/TSP (22 possible, 23 probable, 47 definite). The mean HTLV‐1 proviral load was higher in possible‐ (89,104 ± 93,006 copies/106 PBMC), ‐probable (175,854 ± 128,083 copies/106 PBMC), and definite‐HAM/TSP patients (150,667 ± 122,320 copies/106 PBMC), when compared to asymptomatic individuals (27,178 ± 41,155 copies/106 PBMC) (P < 0.0001). A comparison of all HAM/TSP groups showed the highest proviral loads in probable‐HAM/TSP patients, yet the differences in mean values were not statistically significant. The ROC curve suggested a value of 49,865 copies/106 PBMC, with 87% sensitivity (95% CI = 74–95) and 81% specificity (95% CI = 75–86), as the best proviral load cut‐off point to differentiate definite HAM/TSP patients from asymptomatic individuals. HTLV‐1 proviral loads are higher in groups of infected patients with neurological symptoms and may represent a relevant biological marker of disease progression. J. Med. Virol. 83:1269–1274, 2011. © 2011 Wiley‐Liss, Inc.
Impact of genetic polymorphisms near the IL28B gene and amino acid substitutions in the hepatitis C virus core region on interferon sensitivity/resistance in patients with chronic hepatitis C
Authors: Toyoda Hidenori , Kumada Takashi , Tada Toshifumi , Kawaguchi Takahisa , Murakami Yoshiki , Matsuda Fumihiko
Published: May 2011

It has been reported that genetic polymorphisms near the IL28B gene or amino acid substitutions in hepatitis C virus (HCV) core protein are associated with the clinical outcome of peginterferon (PEG‐IFN) and ribavirin combination therapy. The impact of these factors on the pure sensitivity/resistance to interferon was evaluated. Changes in the HCV RNA levels 24, 48, 72, and 120 hr after administering a single dose of standard interferon (IFN) were measured in 156 HCV‐infected patients. The changes were compared based on the genetic polymorphisms near the IL28B gene or amino acid substitutions in the HCV core region. Among patients with HCV genotype 1b, there were differences in the reduction and subsequent increase in HCV RNA levels after administering IFN based on rs8099917 genetic polymorphisms. Amino acid substitutions at residue 70 were associated with differences in the changes in HCV RNA levels only in patients with TG/GG genotype. Multivariate analyses showed that genetic polymorphisms near the IL28B gene was the sole independent factor that was associated with the reduction in HCV RNA levels after administering IFN and the final response to the combination therapy. Among patients infected with HCV genotype 2a or 2b, there were no differences in the changes in HCV RNA levels based on the genetic polymorphisms near the IL28B gene. In HCV genotype 1b, genetic variations near the IL28B gene affected the sensitivity/resistance to IFN strongly. Genetic polymorphisms near the IL28B gene did not affect the sensitivity/resistance to IFN in HCV genotype 2. J. Med. Virol. 83:1203–1211, 2011. © 2011 Wiley‐Liss, Inc.