bluuebunny/crossref_metadata_2025 huggingface dataset:
Acrolein induces apoptosis through the death receptor pathway in A549 lung cells: role of p53This review is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.
Authors: Roy Julie , Pallepati Pragathi , Bettaieb Ahmed , Averill-Bates Diana A.
Published: April 2010

Acrolein, a highly reactive α,β-unsaturated aldehyde, is an omnipresent environmental pollutant. Chronic and acute human exposures occur through exogenous and endogenous sources, including food, vapors of overheated cooking oil, house and forest fires, cigarette smoke, and automobile exhaust. Acrolein is a toxic byproduct of lipid peroxidation, which has been implicated in pulmonary, cardiac, and neurodegenerative diseases. This study shows that p53 is an initiating factor in acrolein-induced death receptor activation during apoptosis in A549 human lung cells. Exposure of cells to acrolein (0–50 µmol/L) mainly caused apoptosis, which was manifested by execution phase events such as condensation of nuclear chromatin, phosphatidylserine externalization, and poly(ADP-ribose) polymerase (PARP) cleavage. Levels of necrosis (~5%) were low. Acrolein triggered the death receptor pathway of apoptosis, causing elevation of Fas ligand (FasL) and translocation of adaptor protein Fas-associated death domain to the plasma membrane. Acrolein caused activation of caspase-8, caspase-2, caspase-7, and the cross-talk pathway mediated by Bid cleavage. Activation of p53 and increased expression of p53-upregulated modulator of apoptosis (PUMA) occurred in response to acrolein. FasL upregulation and caspase-8 activation were decreased by p53 inhibitor pifithrin-α and antioxidant polyethylene glycol catalase. These findings increase our knowledge about the induction of cell death pathways by acrolein, which has important implications for human health.
Oxidative stress and aging: Is methylglyoxal the hidden enemy?This review is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.
Authors: Desai Kaushik M. , Chang Tuanjie , Wang Hui , Banigesh Ali , Dhar Arti , Liu Jianghai , Untereiner Ashley , Wu Lingyun
Published: April 2010

Aging is a multifactorial process that involves changes at the cellular, tissue, organ and the whole body levels resulting in decreased functioning, development of diseases, and ultimately death. Oxidative stress is believed to be a very important factor in causing aging and age-related diseases. Oxidative stress is caused by an imbalance between oxidants such as reactive oxygen species (ROS) and antioxidants. ROS are produced from the mitochondrial electron transport chain and many oxidative reactions. Methylglyoxal (MG) is a highly reactive dicarbonyl metabolite formed during glucose, protein and fatty acid metabolism. MG levels are elevated in hyperglycemia and other conditions. An excess of MG formation can increase ROS production and cause oxidative stress. MG reacts with proteins, DNA and other biomolecules, and is a major precursor of advanced glycation end products (AGEs). AGEs are also associated with the aging process and age-related diseases such as cardiovascular complications of diabetes, neurodegenerative diseases and connective tissue disorders. AGEs also increase oxidative stress. In this review we discuss the potential role of MG in the aging process through increasing oxidative stress besides causing AGEs formation. Specific and effective scavengers and crosslink breakers of MG and AGEs are being developed and can become potential treatments to slow the aging process and prevent many diseases.
Methods for detecting autophagy and determining autophagy-induced cell deathThis review is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.
Authors: Chen Yongqiang , Azad Meghan B. , Gibson Spencer B.
Published: April 2010

Autophagy is an intracellular lysosomal degradation process, which in the case of macroautophagy, is characterized by the formation of double-membraned autophagosomes. Enhanced under stress conditions, autophagy can function to promote cell survival or cell death depending on the type of cellular stress. Interest in autophagy has increased substantially in the past several years as new research implicates this “self-eating” pathway in cell growth, development, and many human diseases. Various methods have been developed for detecting autophagy; however, the implementation of these methods and the interpretation of the results often vary between studies, and a more standardized approach is required. In this review, we summarize the current methods available for detecting autophagy and for determining its contribution to cell death. Furthermore, we discuss the critical points for the successful application of these methods based on experiences from our laboratory and from other research groups.
Nitric oxide and reactive oxygen species in the nucleus revisitedThis review is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.
Authors: Provost Chantale , Choufani Faten , Avedanian Levon , Bkaily Ghassan , Gobeil Fernand , Jacques Danielle
Published: April 2010

Recent work from our group showed that the nuclear envelope membranes contain several G protein-coupled receptors, including prostaglandin E2 (EP3R) and endothelin-1 (ET-1) receptors. Activation of EP3R increased endothelial nitric oxide synthase (eNOS) RNA expression in nuclei. eNOS and inducible NOS (iNOS) are reported to also be present at the nuclear level. Furthermore, reactive oxygen species (ROS) were also localized at the nuclear level. In this review, we show that stimulation with NO donor sodium nitroprusside results in an increase of intranuclear calcium that was dependent on guanylate cyclase activation, but independent of MAPK. This increase in nuclear calcium correlated with an increase in nuclear transcription of iNOS. H2O2 and ET-1 increase both cytosolic and nuclear ROS in human endocardial endothelial cells and in human aortic vascular smooth muscle cells. This increase in ROS levels by H2O2 and ET-1 was reversed by the antioxidant glutathione. In addition, our results strongly suggest that cytosolic signalization is not only transmitted to the nucleus but is also generated by the nucleus. Furthermore, we demonstrate that oxidative stress can be sensed by the nucleus. These results highly suggest that ROS formation is also generated directly by the nucleus and that free radicals may contribute to ET-1 regulation of nuclear Ca2+ homeostasis.
Ischemia–reperfusion-induced changes in sarcolemmal Na+/K+-ATPase are due to the activation of calpain in the heartThis article is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.
Authors: Singh Raja B. , Dhalla Naranjan S.
Published: April 2010

Depression in cardiac performance due to ischemia–reperfusion (I/R) injury is associated with the development of oxidative stress and decreased sarcolemmal (SL) Na+/K+-ATPase activity. Since both I/R and oxidative stress have been reported to promote the occurrence of intracellular Ca2+ overload and activate proteases such as calpain, this study was undertaken to investigate whether the activation of calpain in I/R hearts is associated with alterations in the SL Na+/K+-ATPase activity and its isoform content. For this purpose, isolated rat hearts treated with and without 2 different calpain inhibitors (leupeptin and MDL28170) were subjected to 30 min ischemia followed by 60 min of reperfusion, and the cardiac function, SL Na+/K+-ATPase activity, Na+/K+-ATPase isoform protein content, and calpain activity were measured. The I/R-induced depressions in cardiac function, Na+/K+-ATPase activity, and protein content of Na+/K+-ATPase isoforms were associated with an increase in calpain activity , but were prevented by treatment of hearts with leupeptin. Incubation of SL membranes with calpain decreased the Na+/K+-ATPase activity and protein content of its isoforms; these changes were also attenuated by leupeptin. The I/R-induced alterations in cardiac function and the activity of SL Na+/K+-ATPase and calpain were Ca2+-dependent and were prevented by MDL28170, a specific inhibitor of calpain. The I/R-induced translocation of calpain isoforms (I and II) from the cytosol to SL and the changes in distribution of calpastatin were also attenuated by treatment with calpain inhibitors. These results suggest that the depression in cardiac function and SL Na+/K+-ATPase activity in I/R hearts may be due to changes in the activity and translocation of calpain.
Adventitial fibroblasts in vascular structure and function: the role of oxidative stress and beyondThis review is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.
Authors: Wang Hui Di , Rätsep Matthew T. , Chapman Alexander , Boyd Ryan
Published: April 2010

The vascular adventitia, defined as the area between the external elastic lamina and the outermost edge of the blood vessel, is composed primarily of fibroblasts and for years was thought to be merely a passive structural support for the blood vessel. Consequently, studies pertaining to the role of the adventitia in regulating vascular function have been far outnumbered by those regarding the vascular endothelium. However, recent work has begun to reveal the dynamic properties of the adventitia. It was therefore the aim of this review to provide an overview of the existing knowledge demonstrating the role of the adventitia in regulating vessel structure and function. The main topics covered in this review include the cellular composition of the adventitia and the role of the adventitia in vascular oxidative stress, vasomotor responses, extracellular matrix protein expression, growth factor expression, and endothelin-1 (ET-1) expression. Recent evidence suggests that the adventitia is a major producer of vascular reactive oxygen species. It displays a distinct response to injury, hypoxia, and pulmonary hypertension, mediating vascular remodelling, repair, and extracellular matrix deposition. It may also play a role in regulating vascular tone. More recently, it has been reported that adventitial fibroblasts can produce ET-1 after Ang II treatment. Additionally, emerging evidence suggests that the adventitia may be a potent source of vasoactive hormones such as growth factors and ET-1, which may regulate vascular structure and function via autocrine or paracrine signalling mechanisms. Despite these findings, many important questions regarding the role of the vascular adventitia remain unanswered, suggesting the need for further research to determine its exact function in health and disease.
Phospholipase C as a potential target for cardioprotection during oxidative stressThis review is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.
Authors: Tappia Paramjit S. , Asemu Girma , Rodriguez-Leyva Delfin
Published: April 2010

Cardiac dysfunction due to ischemia–reperfusion (I/R) is associated with marked changes in membrane function and subsequent Ca2+-handling abnormalities in cardiomyocytes. The membrane abnormalities in hearts subjected to I/R arise primarily from oxidative stress as a consequence of increased formation of reactive oxygen species and other oxidants, as well as reduced antioxidant defenses. Little is known, however, about the nature and mechanisms of the sarcolemmal membrane changes with respect to phospholipase C (PLC)-related signaling events. In addition, the mechanisms involved in protection of the postischemic myocardium and in ischemic preconditioning with respect to PLC function need to be established. Accordingly, this article reviews the historical and current information on PLC-mediated signal transduction mechanisms in I/R, as well as outlining future directions that should be addressed. Such information will extend our knowledge of ischemic heart disease and help improve its therapy.
THE HIERARCHY PROBLEM, RADION MASS, LOCALIZATION OF GRAVITY AND 4D EFFECTIVE NEWTONIAN POTENTIAL IN STRING THEORY ON S1/Z2
Authors: WANG ANZHONG , SANTOS N. O.
Published: April 2010

In this paper, we present a systematical study of braneworlds of string theory on S1/Z2. In particular, starting with the toroidal compactification of the Neveu–Schwarz/Neveu–Schwarz sector in D + d dimensions, we first obtain an effective D-dimensional action, and then compactify one of the D - 1 spatial dimensions by introducing two orbifold branes as its boundaries. We divide the whole set of the gravitational and matter field equations into two groups, one holds outside the two branes, and the other holds on them. By combining the Gauss–Codacci and Lanczos equations, we write down explicitly the general gravitational field equations on each of the two branes, while using distribution theory we express the matter field equations on the branes in terms of the discontinuities of the first derivatives of the matter fields. Afterwards, we address three important issues: (i) the hierarchy problem; (ii) the radion mass; and (iii) the localization of gravity, the four-dimensional Newtonian effective potential and the Yukawa corrections due to the gravitational high-order Kaluza–Klein (KK) modes. The mechanism of solving the hierarchy problem is essentially the combination of the large extra dimension and warped factor mechanisms together with the tension coupling scenario. With very conservative arguments, we find that the radion mass is of the order of 10-2 GeV. The gravity is localized on the visible brane, and the spectrum of the gravitational KK modes is discrete and can be of the order of TeV. The corrections to the four-dimensional Newtonian potential from the higher order of gravitational KK modes are exponentially suppressed and can be safely neglected in current experiments. In an appendix, we also present a systematical and pedagogical study of the Gauss–Codacci equations and Israel's junction conditions across a (D - 1)-dimensional hypersurface, which can be either spacelike or timelike.
ISOMETRY-PRESERVING BOUNDARY CONDITIONS IN THE KERR/CFT CORRESPONDENCE
Authors: RASMUSSEN JØRGEN
Published: April 2010

The near-horizon geometries of the extremal Kerr black hole and certain generalizations thereof are considered. Their isometry groups are all given by SL (2, ℝ)× U (1). The usual boundary conditions of the Kerr/CFT correspondence enhance the U(1) isometry to a Virasoro algebra. Various alternatives to these boundary conditions are explored. Partial classifications are provided of the boundary conditions enhancing the SL (2, ℝ) isometries or separately the U(1) isometry to a Virasoro algebra. In the case of SL (2, ℝ)-enhancing boundary conditions of a near-horizon geometry of the type considered, the conserved charges associated to the generators of the asymptotic Virasoro symmetry form a centreless Virasoro algebra.
THE HYBRID TRACKING SYSTEM OF ATLAS
Authors: ROSSI LEONARDO
Published: April 2010

The central tracker of the ATLAS experiment is built using both silicon and gaseous detectors immersed in a 2 T solenoidal magnetic field. To better match the topology of the tracks emerging from the proton–proton collisions, the tracker is separated into a central barrel part (measuring below pseudorapidity |η|≈1.2) and two end-caps (measuring from ≈1.2 to 2.5). Different technologies are used at different radii to optimize the cost–performance ratio. The innermost part, immediately surrounding the beam pipe and up to ≈15 cm , is made up of silicon pixels for best pattern recognition and maximal radiation resistance. The intermediate region (radii from 30 to 60 cm) uses microstrip detectors and provides excellent space resolution over a large area. The outer layer (radii from 60 to 95 cm) is made up of a large number of small diameter drift tubes (straws) which provide good space resolution in the track bending plane and greatly contribute to pattern recognition with multiple measurements. The transition radiation detection capability of this gaseous detector also helps in electron identification.
Subject-Specific Muscle Synergies in Human Balance Control Are Consistent Across Different Biomechanical Contexts
Authors: Torres-Oviedo Gelsy , Ting Lena H.
Published: April 2010

The musculoskeletal redundancy of the body provides multiple solutions for performing motor tasks. We have proposed that the nervous system solves this unconstrained problem through the recruitment of motor modules or functional muscle synergies that map motor intention to action. Consistent with this hypothesis, we showed that trial-by-trial variations in muscle activation for multidirectional balance control in humans were constrained by a small set of muscle synergies. However, apparent muscle synergy structures could arise from characteristic patterns of sensory input resulting from perturbations or from low-dimensional optimal motor solutions. Here we studied electromyographic (EMG) responses for balance control across a range of biomechanical contexts, which alter not only the sensory inflow generated by postural perturbations, but also the muscle activation patterns used to restore balance. Support-surface translations in 12 directions were delivered to subjects standing in six different postural configurations: one-leg, narrow, wide, very wide, crouched, and normal stance. Muscle synergies were extracted from each condition using nonnegative matrix factorization. In addition, muscle synergies from the normal stance condition were used to reconstruct muscle activation patterns across all stance conditions. A consistent set of muscle synergies were recruited by each subject across conditions. When balance demands were extremely different from the normal stance (e.g., one-legged or crouched stance), task-specific muscle synergies were recruited in addition to the preexisting ones, rather generating de novo muscle synergies. Taken together, our results suggest that muscle synergies represent consistent motor modules that map intention to action, regardless of the biomechanical context of the task.
Spatiotemporal Frequency Tuning Dynamics of Neurons in the Owl Visual Wulst
Authors: Pinto Lucas , Baron Jerome
Published: April 2010

The transformation of spatial (SF) and temporal frequency (TF) tuning functions from broad-band/low-pass to narrow band-pass profiles is one of the key emergent properties of neurons in the mammalian primary visual cortex (V1). The mechanisms underlying such transformation are still a matter of ongoing debate. With the aim of providing comparative insights into the issue, we analyzed various aspects of the spatiotemporal tuning dynamics of neurons in the visual wulst of four awake owls. The wulst is the avian telencephalic target of the retinothalamofugal pathway and, in owls, bears striking functional analogy with V1. Most neurons in our sample exhibited fast and large-magnitude adaptation to the visual stimuli with response latencies very similar to those reported for V1. Moreover, latency increased as a function of stimulus SF but not TF, which suggests that parvo- and magno-like geniculate inputs could be converging onto single wulst neurons. No net shifts in preferred SF or TF were observed along the initial second of stimulation, but bandwidth decreased roughly during the first 200 ms after response latency for both stimulus dimensions. For SF, this occurred exclusively as a consequence of low-frequency suppression, whereas suppression was observed both at the low- and high-frequency limbs of TF tuning curves. Overall these results indicate that SF and TF tuning curves in the wulst are shaped by both feedforward and intratelencephalic suppressive mechanisms, similarly to what seems to be the case in the mammalian striate cortex.
Salmonid genomes have a remarkably expandedakirinfamily, coexpressed with genes from conserved pathways governing skeletal muscle growth and catabolism
Authors: Macqueen Daniel J. , Kristjánsson Bjarni K. , Johnston Ian A.
Published: April 2010

Metazoan akirin genes regulate innate immunity, myogenesis, and carcinogenesis. Invertebrates typically have one family member, while most tetrapod and teleost vertebrates have one to three. We demonstrate an expanded repertoire of eight family members in genomes of four salmonid fishes, owing to paralog preservation after three tetraploidization events. Retention of paralogs secondarily lost in other teleosts may be related to functional diversification and posttranslational regulation. We hypothesized that salmonid akirins would be transcriptionally regulated in fast-twitch skeletal muscle during activation of conserved pathways governing catabolism and growth. The in vivo nutritional state of Arctic charr ( Salvelinus alpinus L.) was experimentally manipulated, and transcript levels for akirin family members and 26 other genes were measured by quantitative real-time PCR (qPCR), allowing the establishment of a similarity network of expression profiles. In fasted muscle, a class of akirins was upregulated, with one family member showing high coexpression with catabolic genes coding the NF-κB p65 subunit, E2 ubiquitin-conjugating enzymes, E3 ubiquitin ligases, and IGF-I receptors. Another class of akirin was upregulated with subsequent feeding, coexpressed with 14-3-3 protein genes. There was no similarity between expression profiles of akirins with IGF hormones or binding protein genes. The level of phylogenetic relatedness of akirin family members was not a strong predictor of transcriptional responses to nutritional state, or differences in transcript abundance levels, indicating a complex pattern of regulatory evolution. The salmonid akirins epitomize the complexity linking the genome to physiological phenotypes of vertebrates with a history of tetraploidization.
Dietary iron-deficient anemia induces a variety of metabolic changes and even apoptosis in rat liver: a DNA microarray study
Authors: Kamei Asuka , Watanabe Yuki , Ishijima Tomoko , Uehara Mariko , Arai Soichi , Kato Hisanori , Nakai Yuji , Abe Keiko
Published: April 2010

Anemia can be induced by dietary iron deficiency, as well as by hemorrhagia. It may also be associated with changes in lipid metabolism. However, no global analysis detailing the consequences of iron deficiency in the liver has yet been conducted. Since the liver is a metabolically important organ and also a major iron-storing organ, we performed a comprehensive transcriptome analysis to determine the effects of iron deficiency on hepatic gene expression. Four-week-old rats were fed an iron-deficient diet, ∼3 ppm iron, ad libitum for 16 days. These rats were compared with similar rats pair-fed a control diet with a normal iron level, 48 ppm iron. The 16-day iron-deficient diet apparently induced anemia. On day 17, the rats were killed under anesthesia, and their livers were dissected for DNA microarray analysis. We identified 600 upregulated and 500 downregulated probe sets that characterized the iron-deficient diet group. In the upregulated probe sets, genes involved in cholesterol, amino acid, and glucose metabolism were significantly enriched, while genes related to lipid metabolism were significantly enriched in the downregulated probe sets. We also found that genes for caspases 3 and 12, which mediate endoplasmic reticulum (ER)-specific apoptosis, were upregulated in the iron-deficient group. Combined, these results suggest that iron deficiency exerts various influences, not only on nutrient metabolism but also on apoptosis, as a consequence of ER stress in the liver.
Two New Species of the GenusThoracophorusMotschulsky, 1837 (Coleoptera: Staphylinidae, Osoriinae) with Remarks on Ecology of the Genus in the Neotropical Region
Authors: Irmler Ulrich
Published: April 2010

The new speciesThoracophorus venezuelanusandT. silvaticusare described. The ecological information from labels and that produced by more detailed studies in Central Amazonia indicate that tree canopies and tree trunks are main habitats ofThoracophorusspecies, and that many species might be associated with ants or termites.
Maximal Regularity for Flexible Structural Systems in Lebesgue Spaces
Authors: Fernández Claudio , Lizama Carlos , Poblete Verónica
Published: April 2010

We study abstract equations of the form λu′′′(t) + u′′(t) = c2Au(t) + c2μAu′(t) + f(t), 0 < λ < μ which is motivated by the study of vibrations of flexible
structures possessing internal material damping. We introduce the notion of (α; β; γ)‐regularized families, which is a particular case of (a; k)‐regularized families, and characterize
maximal regularity in Lp‐spaces based on the technique of Fourier multipliers. Finally, an application with the Dirichlet‐Laplacian in a bounded smooth domain is
given.
Wavelet‐Based Image Registration and Segmentation Framework for the QuantitativeEvaluation of Hydrocephalus
Authors: Luo Fan , Evans Jeanette W. , Linney Norma C. , Schmidt Matthias H. , Gregson Peter H.
Published: April 2010

Hydrocephalus, characterized by increased fluid in the cerebral ventricles, is traditionally evaluated by a visual
assessment of serial CT scans. The complex shape of the ventricular system makes accurate visual comparison
of CT scans difficult. The current research developed a quantitative method to measure the change in cerebral
ventricular volume over time. Key elements of the developed framework are: adaptive image registration based
on mutual information and wavelet multiresolution analysis; adaptive segmentation with novel feature extraction
based on the Dual‐Tree Complex Wavelet Transform; volume calculation. The framework, when tested on
physical phantoms, had an error of 2.3%. When validated on clinical cases, results showed that cases deemed to be
normal/stable had a calculated volume change less than 5%. Those with progressive/treated hydrocephalus had a
calculated change greater than 20%. These findings indicate that the framework is reasonable and has potential for
development as a tool in the evaluation of hydrocephalus.
Expression and Immunogenicity of the Mycobacterial Ag85B/ESAT-6 Antigens Produced in Transgenic Plants by Elastin-Like Peptide Fusion Strategy
Authors: Floss Doreen Manuela , Mockey Michael , Zanello Galliano , Brosson Damien , Diogon Marie , Frutos Roger , Bruel Timothée , Rodrigues Valérie , Garzon Edwin , Chevaleyre Claire , Berri Mustapha , Salmon Henri , Conrad Udo , Dedieu Laurence
Published: April 2010

This study explored a novel system combining plant-based production and the elastin-like peptide (ELP) fusion strategy to produce vaccinal antigens against tuberculosis. Transgenic tobacco plants expressing the mycobacterial antigens Ag85B and ESAT-6 fused to ELP (TBAg-ELP) were generated. Purified TBAg-ELP was obtained by the highly efficient, cost-effective, inverse transition cycling (ICT) method and tested in mice. Furthermore, safety and immunogenicity of the crude tobacco leaf extracts were assessed in piglets. Antibodies recognizing mycobacterial antigens were produced in mice and piglets. A T-cell immune response able to recognize the native mycobacterial antigens was detected in mice. These findings showed that the native Ag85B and ESAT-6 mycobacterial B- and T-cell epitopes were conserved in the plant-expressed TBAg-ELP. This study presents the first results of an efficient plant-expression system, relying on the elastin-like peptide fusion strategy, to produce a safe and immunogenic mycobacterial Ag85B-ESAT-6 fusion protein as a potential vaccine candidate against tuberculosis.
Suppression of Inflammatory Mediators by Cruciferous Vegetable-Derived Indole-3-Carbinol and Phenylethyl Isothiocyanate in Lipopolysaccharide-Activated Macrophages
Authors: Tsai Jo-Ting , Liu Hui-Ching , Chen Yue-Hwa
Published: April 2010

This study was aimed to examine the effects of indole-3-carbinol (I3C) andβ-phenylethyl isothiocyanate (PEITC), bioactive components present in cruciferous vegetable, on the production of inflammatory mediators, including nitric oxide (NO), tumor necrosis factor-α(TNF-α) and interleukin-10 (IL-10), in lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophages. Possible mechanisms of the NO-inhibitory effects were also explored. The results indicated that I3C and PEITC inhibited NO production, and this suppression was associated with decreased production of TNF-αand IL-10 by activated macrophages. In addition, I3C suppressed NO production even after the inducible nitric oxide synthase (iNOS) protein had been produced, but such an inhibitory effect was not observed in cells treated with PEITC. Furthermore, both compounds reduced the NO contents generated from an NO donor in a cell-free condition, suggesting that the increased NO clearance may have contributed to the NO-inhibitory effects. In summary, both I3C and PEITC possessed antiinflammatory effects by inhibiting the productions of NO, TNF-α, and IL-10, although the NO-inhibitory effects may have involved in different mechanisms.
Rotavirus-Like Particles: A Novel Nanocarrier for the Gut
Authors: Cortes-Perez Naima G. , Sapin Catherine , Jaffrelo Loïc , Daou Sabine , Grill Jean Pierre , Langella Philippe , Seksik Philippe , Beaugerie Laurent , Chwetzoff Serge , Trugnan Germain
Published: April 2010

The delivery of bioactive molecules directly to damaged tissues represents a technological challenge. We propose here a new system based on virus-like particles (VLP) from rotavirus, with a marked tropism for the gut to deliver bio-active molecules to intestinal cells. For this, nonreplicative VLP nanoparticles were constructed using a baculovirus expression system and used to deliver an exogenous biomolecule, the green fluorescent protein (GFP), into either MA104 cells or intestinal cells from healthy and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-treated mice. Our results show that expression of rotavirus capsid proteins in baculovirus led to the auto assembly of VLP that display similar properties to rotavirus. In vitro experiments showed that VLP were able to enter into MA104 cells and deliver the reporter protein. Intragastric administration of fluorescent VLP in healthy and TNBS-treated mice resulted in the detection of GFP and viral proteins in intestinal samples. Our results demonstrate an efficient entry of non-replicative rotavirus VLP into the epithelial cell line MA104 and provide the first in vivo evidence of the potential of these nanoparticles as a promising safe candidate for drug delivery to intestinal cells.
Common Fixed Point Theorem for Non-Self Mappings Satisfying Generalized Ćirić Type Contraction Condition in Cone Metric Space
Authors: Sumitra R , Rhymend Uthariaraj V , Hemavathy R , Vijayaraju P
Published: April 2010

We prove common fixed point theorem for coincidentally commuting nonself mappings satisfying generalized contraction condition of Ćirić type in cone metric space. Our results generalize and extend all the recent results related to non-self mappings in the setting of cone metric space.
Role of RELAP/SCDAPSIM in Nuclear Safety
Authors: Allison C. M. , Hohorst J. K.
Published: April 2010

The RELAP/SCDAPSIM code, designed to predict the behaviour of reactor systems during normal and accident conditions, is being developed as part of the international SCDAP Development and Training Program (SDTP). SDTP consists of nearly 60 organizations in 28 countries supporting the development of technology, software, and training materials for the nuclear industry. The program members and licensed software users include universities, research organizations, regulatory organizations, vendors, and utilities located in Europe, Asia, Latin America, and the United States. Innovative Systems Software (ISS) is the administrator for the program. RELAP/SCDAPSIM is used by program members and licensed users to support a variety of activities. The paper provides a brief review of some of the more important activities including the analysis of research reactors and Nuclear Power Plants, design and analysis of experiments, and training.
Polymorphisms in Tumour Necrosis Factor Alpha (TNFα) Gene in Patients with Acute Pancreatitis
Authors: Özhan Gül , Yanar Hakan T. , Ertekin Cemalettin , Alpertunga Buket
Published: April 2010

Proinflammatory cytokines, such as tumour necrosis factorα(TNFα), play fundamental roles in the pathogenesis of acute pancreatitis (AP). The aim of this study was to determine if polymorphisms in the TNFαgene are associated with AP. Two polymorphisms located in the promoter region (positions−308and−238) in TNFαgene were determined using polymerase chain reaction- (PCR-) restriction fragment length polymorphism (RFLP) methods in 103 patients with AP and 92 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression analysis adjusted for age, sex, BMI and smoking. The frequencies of TNFαpolymorphisms were both similar in patients with mild or severe pancreatitis, so were in pancreatitis patients and in controls. We suggest that both SNPs of TNFαare not genetic risk factor for AP susceptibility (OR=1.63; 95% CI: 1.13−4.01 for TNFα−308and OR=0.86; 95% CI: 0.75−1.77 for TNFα−238).
Multiple Depth DB Tables Indexing on the Sphere
Authors: Nicastro Luciano , Calderone Giorgio
Published: April 2010

Any project dealing with large astronomical datasets should consider the use of a relational database server (RDBS). Queries requiring quick selections on sky regions, objects cross‐matching and other high‐level data investigations involving sky coordinates could be unfeasible if tables are missing an effective indexing scheme. In this paper we present the Dynamic Index Facility (DIF) software package. By using the HTM and HEALPix sky pixelization schema, it allows a very efficient indexing and management of spherical data stored into MySQL tables. Any table hosting spherical coordinates can be automatically managed by DIF using any number of sky resolutions at the same time. DIF comprises a set of facilities among which SQL callable functions to perform queries on circular and rectangular regions. Moreover, by removing the limitations and difficulties of 2‐d data indexing, DIF allows the full exploitation of the RDBS capabilities. Performance tests on Giga‐entries tables are reported together with some practical usage of the package.
Toll-like Receptor 4 Modulation as a Strategy to Treat Sepsis
Authors: Wittebole X. , Castanares-Zapatero D. , Laterre P. F.
Published: April 2010

Despite a decrease in mortality over the last decade, sepsis remains the tenth leading causes of death in western countries and one of the most common cause of death in intensive care units. The recent discovery of Toll-like receptors and their downstream signalling pathways allowed us to better understand the pathophysiology of sepsis-related disorders. Particular attention has been paid to Toll-like receptor 4, the receptor for Gram-negative bacteria outer membrane lipopolysaccharide or endotoxin. Since most of the clinical trial targeting single inflammatory cytokine in the treatment of sepsis failed, therapeutic targeting of Toll-like receptor 4, because of its central role, looks promising. The purpose of this paper is to focus on the recent data of various drugs targeting TLR4 expression and pathway and their potential role as adjunctive therapy in severe sepsis and septic shock.
On Sumudu Transform and System of Differential Equations
Authors: Kiliçman Adem , Eltayeb Hassan , Agarwal Ravi P.
Published: April 2010

The regular system of differential equations with convolution terms solved by Sumudu transform.
Repetitive Electric Stimulation Elicits Enduring Improvement of Sensorimotor Performance in Seniors
Authors: Kalisch Tobias , Tegenthoff Martin , Dinse Hubert R.
Published: April 2010

Age-related changes occur on all stages of the human somatosensory pathway, thereby deteriorating tactile, haptic, and sensorimotor performance. However, recent studies show that age-related changes are not irreversible but treatable through peripheral stimulation paradigms based on neuroplasticity mechanisms. We here applied repetitive electric stimulation (rES) to the fingers on a bi-weekly basis for 4 weeks to induce enduring amelioration of age-related changes in healthy individuals aged 60–85 years. Tactile, haptic, and motor performance gradually improved over time of intervention. After termination of rES, tactile acuity recovered to baseline within 2 weeks, while the gains in haptic and motor performance were preserved for 2 weeks. Sham stimulation showed no comparable changes. Our data indicate that age-related decline of sensorimotor performance can be ameliorated by rES and can be stabilized by the repeated application. Thus, long-term application of rES appears as a prime candidate for maintaining sensorimotor functions in elderly individuals.
Zenga′s New Index of Economic Inequality, Its Estimation, and an Analysis of Incomes in Italy
Authors: Greselin Francesca , Pasquazzi Leo , Zitikis Ričardas
Published: April 2010

For at least a century academics and governmental researchers have been developing measures that would aid them in understanding income distributions, their differences with respect to geographic regions, and changes over time periods. It is a fascinating area due to a number of reasons, one of them being the fact that different measures, or indices, are needed to reveal different features of income distributions. Keeping also in mind that the notions of poor and rich are relative to each other, Zenga (2007) proposed a new index of economic inequality. The index is remarkably insightful and useful, but deriving statistical inferential results has been a challenge. For example, unlike many other indices, Zenga′s new index does not fall into the classes of L‐, U‐, and V‐statistics. In this paper we derive desired statistical inferential results, explore their performance in a simulation study, and then use the results to analyze data from the Bank of Italy Survey on Household Income and Wealth (SHIW).
Repertoire Development and the Control of Cytotoxic/Effector Function in Human γδ T Cells
Authors: Urban Elizabeth M. , Chapoval Andrei I. , Pauza C. David
Published: April 2010

T cells develop into two major populations distinguished by their T cell receptor (TCR) chains. Cells with the αβ TCR generally express CD4 or CD8 lineage markers and mostly fall into helper or cytotoxic/effector subsets. Cells expressing the alternate γδ TCR in humans generally do not express lineage markers, do not require MHC for antigen presentation, and recognize nonpeptidic antigens. We are interested in the dominant Vγ2Vδ2+ T cell subset in human peripheral blood and the control of effector function in this population. We review the literature on γδ T cell generation and repertoire selection, along with recent work on CD56 expression and defining a cytotoxic/effector lineage within the phosphoantigen‐reactive Vγ2Vδ2 cells. A unique mechanism for MHC‐independent repertoire selection is linked to the control of effector function that is vital to the role for γδ T cells in tumor surveillance. Better understanding of these mechanisms will improve our ability to exploit this population for tumor immunotherapy.
5-Fluorouracil Selectively Kills Tumor-Associated Myeloid-Derived Suppressor Cells Resulting in Enhanced T Cell–Dependent Antitumor Immunity
Authors: Vincent Julie , Mignot Grégoire , Chalmin Fanny , Ladoire Sylvain , Bruchard Mélanie , Chevriaux Angélique , Martin François , Apetoh Lionel , Rébé Cédric , Ghiringhelli François
Published: April 2010

Myeloid-derived suppressor cells (MDSC) accumulate in the spleen and tumor bed during tumor growth. They contribute to the immune tolerance of cancer notably by inhibiting the function of CD8(+) T cells. Thus, their elimination may hamper tumor growth by enhancing antitumor T-cell functions. We have previously reported that some anticancer agents relied on T cell–dependent anticancer responses to achieve maximal efficacy. However, the effect of anticancer agents on MDSC has remained largely unexplored. In this study, we observed that gemcitabine and 5-fluorouracil (5FU) were selectively cytotoxic on MDSC. In vivo, the treatment of tumor-bearing mice with 5FU led to a major decrease in the number of MDSC in the spleens and tumor beds of animals whereas no significant effect on T cells, natural killer cells, dendritic cells, or B cells was noted. Interestingly, 5FU showed a stronger efficacy over gemcitabine to deplete MDSC and selectively induced MDSC apoptotic cell death in vitro and in vivo. The elimination of MDSC by 5FU increased IFN-γ production by tumor-specific CD8(+) T cells infiltrating the tumor and promoted T cell–dependent antitumor responses in vivo. Altogether, these findings suggest that the antitumor effect of 5FU is mediated, at least in part, by its selective cytotoxic action on MDSC. Cancer Res; 70(8); 3052–61. ©2010 AACR.
Integrin α4β1 Signaling Is Required for Lymphangiogenesis and Tumor Metastasis
Authors: Garmy-Susini Barbara , Avraamides Christie J. , Schmid Michael C. , Foubert Philippe , Ellies Lesley G. , Barnes Leo , Feral Chloe , Papayannopoulou Thalia , Lowy Andrew , Blair Sarah L. , Cheresh David , Ginsberg Mark , Varner Judith A.
Published: April 2010

Recent studies have shown that lymphangiogenesis or the growth of lymphatic vessels at the periphery of tumors promotes tumor metastasis to lymph nodes. We show here that the fibronectin-binding integrin α4β1 and its ligand fibronectin are novel functional markers of proliferative lymphatic endothelium. Tumors and lymphangiogenic growth factors, such as vascular endothelial growth factor-C (VEGF-C) and VEGF-A, induce lymphatic vessel expression of integrin α4β1. Integrin α4β1 then promotes growth factor and tumor-induced lymphangiogenesis, as genetic loss of integrin α4β1 expression in Tie2Cre+ α4loxp/loxp mice or genetic loss of α4 signaling in α4Y991A knock-in mice blocks growth factor and tumor-induced lymphangiogenesis, as well as tumor metastasis to lymph nodes. In addition, antagonists of integrin α4β1 suppress lymphangiogenesis and tumor metastasis. Our studies show that integrin α4β1 and the signals it transduces regulate the adhesion, migration, invasion, and survival of proliferating lymphatic endothelial cells. As suppression of α4β1 expression, signal transduction, or function in tumor lymphatic endothelium not only inhibits tumor lymphangiogenesis but also prevents metastatic disease, these results show that integrin α4β1–mediated tumor lymphangiogenesis promotes metastasis and is a useful target for the suppression of metastatic disease. Cancer Res; 70(8); 3042–51. ©2010 AACR.
Astrocyte Elevated Gene-1 Upregulates Matrix Metalloproteinase-9 and Induces Human Glioma Invasion
Authors: Liu Liping , Wu Jueheng , Ying Zhe , Chen Baixue , Han Anjia , Liang Yingjie , Song Libing , Yuan Jie , Li Jun , Li Mengfeng
Published: April 2010

The poor prognosis of malignant gliomas is largely attributed to their highly invasive nature. The molecular mechanism underlying the invasiveness of glioma cells, however, remains to be elucidated. The present study found that astrocyte elevated gene-1 (AEG-1) was upregulated in human glioma cell lines and glioma tissues compared with normal astrocytes and brain tissues. AEG-1 was found to be upregulated in 265 of 296 (89.5%) glioma sections, and the AEG-1 expression level significantly correlated with clinicopathologic stages of gliomas. Ectopic expression or short hairpin RNA silencing of AEG-1 significantly enhanced or inhibited, respectively, the invasive ability of glioma cells. At the molecular level, we showed that upregulated AEG-1 in glioma cells interacted with matrix metalloproteinase-9 (MMP-9) promoter and transactivated MMP-9 expression, whereas knockdown of AEG-1 expression reduced the level of MMP-9. Two regions in MMP-9 promoter were found to be involved in the interaction with AEG-1. Suppression of endogenous MMP-9 abrogated the effects of AEG-1 on invasiveness. Consistent with these observations, immunostaining analysis revealed a significant correlation between the expressions of AEG-1 and MMP-9 in a cohort of clinical glioma samples. Moreover, intracranial xenografts of glioma cells engineered to express AEG-1 were highly invasive compared with the parental cells and expressed high level of MMP-9. Collectively, these findings provide evidence that AEG-1 contributes to glioma progression by enhancing MMP-9 transcription and, hence, tumor cell invasiveness, and underscore the importance of AEG-1 in glioma development and progression. Cancer Res; 70(9); 3750–9. ©2010 AACR.
Pseudopodial Actin Dynamics Control Epithelial-Mesenchymal Transition in Metastatic Cancer Cells
Authors: Shankar Jay , Messenberg Anat , Chan Jackie , Underhill T. Michael , Foster Leonard J. , Nabi Ivan R.
Published: April 2010

A key cellular process associated with the invasive or metastatic program in many cancers is the transformation of epithelial cells toward a mesenchymal state, a process called epithelial to mesenchymal transition or EMT. Actin-dependent protrusion of cell pseudopodia is a critical element of mesenchymal cell migration and therefore of cancer metastasis. However, whether EMT occurs in human cancers and, in particular, whether it is a prerequisite for tumor cell invasion and metastasis, remains a subject of debate. Microarray and proteomic analysis of actin-rich pseudopodia from six metastatic human tumor cell lines identified 384 mRNAs and 64 proteins common to the pseudopodia of six metastatic human tumor cell lines of various cancer origins leading to the characterization of 19 common pseudopod-specific proteins. Four of these (AHNAK, septin-9, eIF4E, and S100A11) are shown to be essential for pseudopod protrusion and tumor cell migration and invasion. Knockdown of each of these proteins in metastatic cells resulted in reduced actin cytoskeleton dynamics and induction of mesenchymal-epithelial transition (MET) that could be prevented by the stabilization of the actin cytoskeleton. Actin-dependent pseudopodial protrusion and tumor cell migration are therefore determinants of EMT. Protein regulators of pseudopodial actin dynamics may represent unique molecular targets to induce MET and thereby inhibit the metastatic potential of tumor cells. Cancer Res; 70(9); 3780–90. ©2010 AACR.
Oncogenic Role of miR-483-3p at the IGF2/483 Locus
Authors: Veronese Angelo , Lupini Laura , Consiglio Jessica , Visone Rosa , Ferracin Manuela , Fornari Francesca , Zanesi Nicola , Alder Hansjuerg , D'Elia Gemma , Gramantieri Laura , Bolondi Luigi , Lanza Giovanni , Querzoli Patrizia , Angioni Adriano , Croce Carlo M. , Negrini Massimo
Published: April 2010

hsa-mir-483 is located within intron 2 of the IGF2 locus. We found that the mature microRNA (miRNA) miR-483-3p is overexpressed in 100% of Wilms' tumors. In addition, colon, breast, and liver cancers exhibit high or even extremely high levels of miR-483-3p in ∼30% of the cases. A coregulation with IGF2 mRNA was detected, although some tumors exhibited high expression of miR-483-3p without a concomitant increase of IGF2. These findings suggested that miR-483-3p could cooperate with IGF2 or act as an autonomous oncogene. Indeed, here we prove that an anti-miRNA oligonucleotide against miR-483-3p could inhibit the miRNAs without affecting IGF2 mRNA and it could suppress tumorigenicity of HepG2 cells, a cell line that overexpresses miR-483-3p and IGF2. Conversely, no antitumor effect was elicited by inhibition of IGF2. The oncogenic mechanism of miR-483-3p was at least partially clarified by the finding that it could modulate the proapoptotic protein BBC3/PUMA and miR-483-3p enforced expression could protect cells from apoptosis. Our results indicate that miR-483-3p could function as an antiapoptotic oncogene in various human cancers and reveal a new, potentially important target for anticancer therapy. Cancer Res; 70(8); 3140–9. ©2010 AACR.