bluuebunny/crossref_metadata_2025_split huggingface dataset:
VEGF inhibitor (Iressa) arrests histone deacetylase expression: Single‐cell cotransfection imaging cytometry for multi‐target‐multi‐drug analysis
Authors: Tak Yu Kyung , Naoghare Pravin K. , Han Eunyoung , Song Joon Myong 
Published: December 2010

AbstractMulti‐target‐multi‐drug approaches are needed to accelerate the process of drug discovery screening and to design efficient therapeutic strategies against diseases that involve alterations in multiple cellular targets. Herein we report single‐cell cotransfection imaging cytometry to quantitatively screen drug‐induced off‐target effects. Vascular endothelial growth factor (VEGF) and histone deacetylase (HDAC) genes amplified from the genomic DNA were cloned in fluorescently tagged gene constructs (RFP‐HDAC/YFP‐VEGF). These gene constructs were cotransfected in HEK‐293 cells to explore the possibility of off‐target effects of 4‐phenylbutyrate and Iressa on the expression of VEGF and HDAC through single‐cell imaging cytometry. Iressa (10 µM) treatment at the time of cotransfection or 48 h after cotransfection of RFP‐HDAC/YFP‐VEGF plasmids in HEK‐293 cells resulted in off‐target effects on HDAC expression. These results suggest possible applications of Iressa in the treatment of diseases in which expression of both HDAC and VEGF should be inhibited. 4‐Phenylbutyrate (2.0 mM) did not show any off‐target effects on VEGF expression. The developed quantitative multicolor live single‐cell cotransfection imaging can be employed to select better drug combinations for faster screening and greater accuracy in multi‐target‐multi‐drug analysis by increasing the on‐target/desired off‐target effects and eliminating the undesirable off‐target effects. J. Cell. Physiol. 226: 2115–2122, 2011. © 2010 Wiley‐Liss, Inc.
HMGB‐1 induces IL‐6 production in human synovial fibroblasts through c‐Src, Akt and NF‐κB pathways
Authors: Hou Chun‐Han , Fong Yi‐Chin , Tang Chih‐Hsin 
Published: December 2010

AbstractHigh mobility group box chromosomal protein 1 (HMGB‐1) is a widely studied, ubiquitous nuclear protein that is present in eukaryotic cells, and plays a crucial role in inflammatory response. However, the effects of HMGB‐1 on human synovial fibroblasts are largely unknown. In this study, we investigated the intracellular signaling pathway involved in HMGB‐1‐induced IL‐6 production in human synovial fibroblast cells. HMGB‐1 caused concentration‐ and time‐dependent increases in IL‐6 production. HMGB‐1‐mediated IL‐6 production was attenuated by receptor for advanced glycation end products (RAGE) monoclonal antibody (Ab) or siRNA. Pretreatment with c‐Src inhibitor (PP2), Akt inhibitor and NF‐κB inhibitor (pyrrolidine dithiocarbamate and L‐1‐tosylamido‐2‐phenylenylethyl chloromethyl ketone) also inhibited the potentiating action of HMGB‐1. Stimulation of cells with HMGB‐1 increased the c‐Src and Akt phosphorylation. HMGB‐1 increased the accumulation of p‐p65 in the nucleus, as well as NF‐κB luciferase activity. HMGB‐1‐mediated increase of NF‐κB luciferase activity was inhibited by RAGE Ab, PP2 and Akt inhibitor or RAGE siRNA, or c‐Src and Akt mutant. Our results suggest that HMGB‐1‐increased IL‐6 production in human synovial fibroblasts via the RAGE receptor, c‐Src, Akt, p65, and NF‐κB signaling pathways. J. Cell. Physiol. 226: 2006–2015, 2011. © 2010 Wiley‐Liss, Inc.
Role of the EGFR ligand/receptor system in the secretion of angiogenic factors in mesenchymal stem cells
Authors: De Luca Antonella , Gallo Marianna , Aldinucci Donatella , Ribatti Domenico , Lamura Luana , D'Alessio Amelia , De Filippi Rosaria , Pinto Antonio , Normanno Nicola 
Published: December 2010

AbstractIncreasing evidence suggests that bone marrow‐derived mesenchymal stem cells (MSCs) are recruited into the stroma of developing tumors where they contribute to cancer progression. MSCs produce different growth factors that sustain tumor‐associated neo‐angiogenesis. Since the majority of carcinomas secrete ligands of the epidermal growth factor receptor (EGFR), we assessed the role of EGFR signaling in regulating the release of angiogenic factors in MSCs. Treatment of human primary MSCs and of the human osteoblastic cell line hFOB with transforming growth factor α (TGF‐α), one of the main ligands of the EGFR, significantly induced activation of this receptor and of different intracellular signaling proteins, including the PI3K/AKT and the MEK/MAPK pathways. TGF‐α induced a significant increase in the levels of secretion of vascular endothelial growth factor in both MSCs and hFOB. Conditioned medium from TGF‐α treated MSCs showed an higher in vivo angiogenic effect as compared with medium from untreated cells. Treatment of MSCs with TGF‐α also produced a significant increase in the secretion of other angiogenic growth factors such as angiopoietin‐2, granulocyte‐colony stimulating factor, hepatocyte growth factor, interleukin (IL)‐6, IL‐8, and platelet‐derived growth factor‐BB. Using selective MEK and PI3K inhibitors, we found that both MEK/MAPK and the PI3K/AKT signaling pathways mediate the ability of TGF‐α to induce secretion of angiogenic factors in MSCs. Finally, stimulation with TGF‐α increased the ability of MSCs to induce migration of MCF‐7 breast cancer cells. These data suggest that EGFR signaling regulates the ability of MSCs to sustain cancer progression through the release of growth factors that promote neo‐angiogenesis and tumor cell migration. J. Cell. Physiol. 226: 2131–2138, 2011. © 2010 Wiley‐Liss, Inc.
Osteopontin controls endothelial cell migration in vitro and in excised human valvular tissue from patients with calcific aortic stenosis and controls
Authors: Poggio Paolo , Grau Juan B. , Field Benjamin C. , Sainger Rachana , Seefried William F. , Rizzolio Flavio , Ferrari Giovanni 
Published: December 2010

AbstractCalcific aortic stenosis (CAS) is a pathological condition of the aortic valve characterized by dystrophic calcification of the valve leaflets. Despite the high prevalence and mortality associated with CAS, little is known about its pathogenetic mechanisms. Characterized by progressive dystrophic calcification of the valve leaflets, the early stages of aortic valve degeneration are similar to the active inflammatory process of atherosclerosis including endothelial disruption, inflammatory cell infiltration, lipid deposition, neo‐vascularization and calcification. In the vascular system, the endothelium is an important regulator of physiological and pathological conditions; however, the contribution of endothelial dysfunction to valvular degeneration at the cellular and molecular level has received little attention. Endothelial cell (EC) activation and neo‐vascularization of the cusps characterizes all stages of aortic valvular degeneration from aortic sclerosis to aortic stenosis. Here we reported the role of osteopontin (OPN) in the regulation of EC activation in vitro and in excised tissue from CAS patients and controls. OPN is an important pro‐angiogenic factor in several pathologies. High levels of OPN have been demonstrated in both tissue and plasma of patients with aortic valve sclerosis and stenosis. The characterization of valvular ECs as a cellular target for OPN will help us uncover the pathogenesis of aortic valve degeneration and stenosis, opening new perspectives for the prevention and therapy of this prevalent disease. J. Cell. Physiol. 226: 2139–2149, 2011. © 2010 Wiley‐Liss, Inc.
A dominant mutation etiologic for human tricho‐dento‐osseous syndrome impairs the ability of DLX3 to downregulate ΔNp63α
Authors: Di Costanzo Antonella , Festa Luisa , Roscigno Giuseppina , Vivo Maria , Pollice Alessandra , Morasso Maria , La Mantia Girolama , Calabrò Viola 
Published: December 2010

AbstractThe homeodomain transcription factors play crucial roles in many developmental processes ranging from organization of the body plan to differentiation of individual tissues. The homeodomain protein Distal‐less‐3 (DLX3) has an essential role in epidermal stratification and development of ectodermal appendages, placenta and bones. A four‐nucleotide deletion in the human DLX3 gene is etiologic for the human hereditary tricho‐dento‐osseous (TDO) ectodermal dysplasia, a dominant syndrome characterized by abnormalities in hair, nails, teeth, and bones. We have previously demonstrated that DLX3 gene expression induces degradation of ΔNp63α, a specific product of the TP63 gene, a master regulator of multi‐layered epithelia. Here we show that the DLX3TDO mutant protein is unable to promote ΔNp63α protein degradation and impairs the expression of cell cycle regulatory proteins and skin differentiation markers. However, we found that in cell expressing equal amounts of mutant and wild‐type DLX3, ΔNp63α protein level is efficiently regulated implying that genetic heterozygosity at the DLX3 locus protects TDO patients from developing severe p63‐associated skin defects. J. Cell. Physiol. 226: 2189–2197, 2011. © 2010 Wiley‐Liss, Inc.
Adipogenic differentiation of human mesenchymal stromal cells is down‐regulated by microRNA‐369‐5p and up‐regulated by microRNA‐371
Authors: Bork Simone , Horn Patrick , Castoldi Mirco , Hellwig Isabelle , Ho Anthony D. , Wagner Wolfgang 
Published: December 2010

AbstractLong‐term culture of human mesenchymal stromal cells (MSC) has implications on their proliferation and differentiation potential and we have demonstrated that this is associated with up‐regulation of the five microRNAs miR‐29c, miR‐369‐5p, miR‐371, miR‐499, and let‐7f. In this study, we examined the role of these senescence‐associated microRNAs for cellular aging and differentiation of MSC. Proliferation was reduced upon transfection with miR‐369‐5p, miR‐371, and miR‐499. Adipogenic differentiation was impaired by miR‐369‐5p whereas it was highly increased by miR‐371. This was accompanied by respective gene expression changes of some adipogenic key molecules (adiponectin and fatty acid‐binding protein 4 [FABP4]). Furthermore luciferase reporter assay indicated that FABP4 is a direct target of miR‐369‐5p. Microarray analysis upon adipogenic or osteogenic differentiation revealed down‐regulation of several microRNAs albeit miR‐369‐5p and miR‐371 were not affected. Expression of the de novo DNA methyltransferases DNMT3A and DNMT3B was up‐regulated by transfection of miR‐371 whereas expression of DNMT3A was down‐regulated by miR‐369‐5p. In summary, we identified miR‐369‐5p and miR‐371 as antagonistic up‐stream regulators of adipogenic differentiation and this might be indirectly mediated by epigenetic modifications. J. Cell. Physiol. 226: 2226–2234, 2011. © 2010 Wiley‐Liss, Inc.
The effect of exercise training on transverse tubules in normal, remodeled, and reverse remodeled hearts
Authors: Kemi Ole J. , Hoydal Morten A. , MacQuaide Niall , Haram Per M. , Koch Lauren G. , Britton Steven L. , Ellingsen Oyvind , Smith Godfrey L. , Wisloff Ulrik 
Published: December 2010

AbstractThe response of transverse (T)‐tubules to exercise training in health and disease remains unclear. Therefore, we studied the effect of exercise training on the density and spacing of left ventricle cardiomyocyte T‐tubules in normal and remodeled hearts that associate with detubulation, by confocal laser scanning microscopy. First, exercise training in normal rats increased cardiomyocyte volume by 16% (P < 0.01), with preserved T‐tubule density. Thus, the T‐tubules adapted to the physiologic hypertrophy. Next, we studied T‐tubules in a rat model of metabolic syndrome with pressure overload‐induced concentric left ventricle hypertrophy, evidenced by 15% (P < 0.01) increased cardiomyocyte size. These rats had only 85% (P < 0.01) of the T‐tubule density of control rats. Exercise training further increased cardiomyocyte volume by 8% (P < 0.01); half to that in control rats, but the T‐tubule density remained unchanged. Finally, post‐myocardial infarction heart failure induced severe cardiac pathology, with a 70% (P < 0.01) increased cardiomyocyte volume that included both eccentric and concentric hypertrophy and 55% (P < 0.01) reduced T‐tubule density. Exercise training reversed 50% (P < 0.01) of the pathologic hypertrophy, whereas the T‐tubule density increased by 40% (P < 0.05) compared to sedentary heart failure, but remained at 60% of normal hearts (P < 0.01). Physiologic hypertrophy associated with conserved T‐tubule spacing (∼1.8–1.9 µm), whereas in pathologic hypertrophy, T‐tubules appeared disorganized without regular spacing. In conclusion, cardiomyocytes maintain the relative T‐tubule density during physiologic hypertrophy and after mild concentric pathologic hypertrophy, whereas after severe pathologic remodeling with a substantial loss of T‐tubules; exercise training reverses the remodeling and partly corrects the T‐tubule density. J. Cell. Physiol. 226: 2235–2243, 2011. © 2010 Wiley‐Liss, Inc.
EGF‐induced ERK‐activation downstream of FAK requires rac1‐NADPH oxidase
Authors: Flinder Liv Ingrid , Timofeeva Olga A. , Rosseland Carola M. , Wierød Lene , Huitfeldt Henrik S. , Skarpen Ellen 
Published: December 2010

AbstractReactive oxygen species (ROS) function as signaling molecules mainly by reversible oxidation of redox‐sensitive target proteins. ROS can be produced in response to integrin ligation and growth factor stimulation through Rac1 and its effector protein NADPH oxidase. One of the central roles of Rac1‐NADPH oxidase is actin cytoskeletal rearrangement, which is essential for cell spreading and migration. Another important regulator of cell spread is focal adhesion kinase (FAK), a coordinator of integrin and growth factor signaling. Here, we propose a novel role for NADPH oxidase as a modulator of the FAK autophosphorylation site. We found that Rac1‐NADPH oxidase enhanced the phosphorylation of FAK at Y397. This site regulates FAK's ability to act as a scaffold for EGF‐mediated signaling, including activation of ERK. Accordingly, we found that EGF‐induced activation of FAK at Y925, the following activation of ERK, and phosphorylation of FAK at the ERK‐regulated S910‐site depended upon NADPH oxidase. Furthermore, the inhibition of NADPH oxidase caused excessive focal adhesions, which is in accordance with ERK and FAK being modulators of focal adhesion dissociation. Our data suggest that Rac1 through NADPH oxidase is part of the signaling pathway constituted by FAK, Rac1, and ERK that regulates focal adhesion disassembly during cell spreading. J. Cell. Physiol. 226: 2267–2278, 2011. © 2010 Wiley‐Liss, Inc.
Trail down‐regulates the release of osteoprotegerin (OPG) by primary stromal cells
Authors: Corallini Federica , Celeghini Claudio , Rimondi Erika , di Iasio Maria Grazia , Gonelli Arianna , Secchiero Paola , Zauli Giorgio 
Published: December 2010

AbstractThe soluble member of the TNF‐R superfamily osteoprotegerin (OPG) is abundantly released under basal conditions by both mesenchymal stem cells (MSC) and fibroblasts and by endothelial cells upon stimulation with inflammatory cytokines. Since MSC, fibroblasts and endothelial cells represent key elements of the normal and tumor microenvironment and express detectable levels of surface TRAIL receptors, we investigated the effect of TRAIL on OPG release. Unexpectedly, recombinant TRAIL decreased the spontaneous OPG release in all cell types examined. Moreover, TRAIL decreased OPG release also in stromal cells co‐cultured with lymphoma cells and counteracted the OPG induction by ${\rm TNF} \hbox{-} {\tilde {\alpha }}$ in HUVEC and MSC. Such down‐regulation was not due to a masking effect in the ELISA quantification of the OPG released in the culture supernatants due to binding of OPG to its ligands (TRAIL and RANKL), as demonstrated by competition experiments with recombinant TRAIL and by the lack of RANKL release/induction. In addition, OPG down‐regulation was not due to induction of cytotoxic effects by TRAIL, since the degree of apoptosis in response to TRAIL was negligible in all primary cell types. With regards to the possible molecular mechanism accounting for the down‐regulation of OPG release by TRAIL, we found that treatment of MSC with TRAIL significantly decreased the phosphorylation levels of p38/MAPK. There is a suggestion that this pathway is involved in the stabilization of OPG mRNA. In this respect, the ability of TRAIL to decrease the release of OPG, in the absence of cell cytotoxicity, was mimicked by the p38/MAPK inhibitor SB203580. J. Cell. Physiol. 226: 2279–2286, 2011. © 2010 Wiley‐Liss, Inc.
Suckermouth armored catfish resolve the paradox of simultaneous respiration and suction attachment: a kinematic study of Pterygoplichthys disjunctivus
Authors: Geerinckx Tom , Herrel Anthony , Adriaens Dominique 
Published: December 2010

AbstractSuckermouth armored catfishes (Loricariidae) use their suckermouth for inspiration, feeding, and attachment to substrates. The sucker consists of a pre‐valvular cavity, formed by a modified lip disc, and is separated from the larger post‐valvular buccal cavity by a muscular oral valve. The combination of respiration and suction attachment seems paradoxal, as a properly functioning suction device would need a sucker without leakage (yet inspiration must occur via the sucker), and continuous subambient pressure in the sucker cavity (even during expiratory mouth floor elevation). In the loricariid Pterygoplichthys disjunctivus, the anatomy of the suckermouth structures was examined, and a kinematic analysis was performed to acquire insights into how respiration and attachment are combined. High‐speed external and X‐ray recordings show that suckermouth attachment influences respiratory parameters such as decreasing excursion amplitudes of mouth floor elements, and the way water enters the mouth via furrows in the lip disc. Respiration, however, continues during attachment and is not blocked. Our data show that the muscular oral valve actively separates the post‐valvular buccal cavity from the pre‐valvular sucker cavity. Volume changes of this pre‐valvular cavity are opposite to those of the post‐valvular cavity and assure sucker function even during expiration. These volume changes are caused by movements of the lower lip, the lower jaws, and the oral valve. The lateral inflow furrow openings, controlled by the maxillary barbels, can occur unilaterally. Morphological and kinematic data also show that the opercle is anatomically and functionally decoupled from the gill opening. J. Exp. Zool. 315:121–131, 2011. © 2010 Wiley‐Liss, Inc.
Developmental transcriptome ofAplysia californica'
Authors: Heyland Andreas , Vue Zer , Voolstra Christian R. , Medina Mónica , Moroz Leonid L. 
Published: December 2010

AbstractGenome‐wide transcriptional changes in development provide important insight into mechanisms underlying growth, differentiation, and patterning. However, such large‐scale developmental studies have been limited to a few representatives of Ecdysozoans and Chordates. Here, we characterize transcriptomes of embryonic, larval, and metamorphic development in the marine molluscAplysia californicaand reveal novel molecular components associated with life history transitions. Specifically, we identify more than 20 signal peptides, putative hormones, and transcription factors in association with early development and metamorphic stages—many of which seem to be evolutionarily conserved elements of signal transduction pathways. We also characterize genes related to biomineralization—a critical process of molluscan development. In summary, our experiment provides the first large‐scale survey of gene expression in mollusc development, and complements previous studies on the regulatory mechanisms underlying body plan patterning and the formation of larval and juvenile structures. This study serves as a resource for further functional annotation of transcripts and genes inAplysia, specifically and molluscs in general. A comparison of theAplysiadevelopmental transcriptome with similar studies in the zebra fishDanio rerio, the fruit flyDrosophila melanogaster, the nematodeCaenorhabditis elegans, and other studies on molluscs suggests an overall highly divergent pattern of gene regulatory mechanisms that are likely a consequence of the different developmental modes of these organisms.J. Exp. Zool. (Mol. Dev. Evol.) 316:113–134, 2011. © 2010 Wiley‐Liss, Inc.
Prophylactic, therapeutic and immune enhancement effect of liposome‐encapsulated PolyICLC on highly pathogenic H5N1 influenza infection
Authors: Li Yi , Hu Yanxin , Jin Yi , Zhang Guozhong , Wong Jonathan , Sun Lun‐Quan , Wang Ming 
Published: December 2010

AbstractBackgroundIn view of the magnitude and severity of outbreaks of the highly pathogenic H5N1 influenza virus (H5N1‐HPIV) and the threat to public health, there is an urgent need to develop broad‐spectrum prophylactic and therapeutic agents against infection by H5N1‐HPIV and other subtypes.Methods and ResultsIn the present study, we explored the use of LE‐PolyICLC, a liposome encapsulated double‐stranded RNA, as a possible prophylactic, therapeutic and immune enhancement agent. In a mouse infection model, we showed that the administration of LE‐PolyICLC intranasally before or shortly after infection could inhibit virus replication, leading to a significant reduction in pulmonary viral titres and a higher survival rate of infected mice. When used as a molecular adjuvant, LE‐PolyICLC significantly enhanced both the humoral and cellular responses elicited by inactivated H5N1 vaccine and augmented the protective efficacy provided by vaccination. Most importantly, the data also demonstrate that LE‐PolyICLC could effectively attenuate the development of pulmonary fibrosis during the restoration period at day 14 after H5N1 infection.ConclusionsTaken together, the data obtained in the present study suggest that strong consideration should be given for the use of LE‐PolyICLC as prophylactic and therapeutic agents and also as a vaccination adjuvant to combat highly pathogenic influenza infection and its associated complications such as pulmonary fibrosis. Copyright © 2011 John Wiley & Sons, Ltd.
The impact of destination attributes on Muslim tourist's choice
Authors: Battour Mohamed , Ismail Mohd Nazari , Battor Moustafa 
Published: December 2010

AbstractThe success of marketing destinations for Muslim tourists could be guided by observing Islamic teachings in tourism activities. This study is a trial to explore which Islamic attributes of destinations could be used a base for tailoring Halal tourist packages. Qualitative data were collected by conducting two focus group discussions and fifty three interviews in Malaysia. Two major aspects are identified which may attract Muslim tourists. Some suggestions are also presented to satisfy Muslim tourists. Copyright © 2010 John Wiley & Sons, Ltd.
Documented combat‐related mental health problems in military noncombatants
Authors: Peterson Alan L. , Wong Vanessa , Haynes Margaret F. , Bush Anneke C. , Schillerstrom Jason E. 
Published: December 2010

AbstractAlthough combat‐related posttraumatic stress disorder (PTSD) has been documented for military combatants, little is known about PTSD in noncombatants. Active‐duty U.S. Air Force noncombatants (N = 5,367) completed a Post‐Deployment Health Assessment upon return from combat zones in Iraq (n = 4,408) or a noncombat zone in Qatar (n = 959). Those deployed to Iraq were significantly more likely to report exposure to someone who was wounded or killed (20.8% vs. 6.3%), feeling in great danger of being killed at some point during deployment (18.9% vs. 3.5%), symptoms of PTSD (4.1% vs. 0.7%), and symptoms of major depression (9.9% vs. 5.4%). These findings suggest that deployment to a war zone is associated with increased mental health problems, even for noncombatants.
DIN 32 625
Authors: Seel Fritz 
Published: December 2010

AbstractDie Norm DIN 32 625, über die im letzten Heft bereits kurz berichtet wurde, ist nicht auf einhellige Begeisterung der Chemiker gestoßen. Wir bringen hier eine kritische Analyse von Prof. Seel (Saarbrücken), auf die noch einmal eine Darstellung aus der Sicht der verantwortlichen Kommission folgt; dieser Text ist in leicht veränderter Form bereits früher im Mitteilungsblatt der Fachgruppe “Analytische Chemie” der GDCh (Springer–Verlag) erschienen.