bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epithelial–mesenchymal transition induced by biliary innate immunity contributes to the sclerosing cholangiopathy of biliary atresia
Authors: Harada Kenichi , Sato Yasunori , Ikeda Hiroko , Isse Kumiko , Ozaki Satoru , Enomae Mio , Ohama Kazunori , Katayanagi Kazuyoshi , Kurumaya Hiroshi , Matsui Akira , Nakanuma Yasuni 
Published: November 2008

AbstractInfections of Reoviridae consisting of a double‐stranded RNA (dsRNA) genome and the biliary innate immune response to dsRNA are implicated in the aetiopathogenesis of biliary atresia (BA). Epithelial–mesenchymal transition (EMT) has recently been proposed as a mechanism behind the sclerosing cholangitis in BA. We hypothesized that the innate immune response to dsRNA in biliary epithelial cells plays an important role in peribiliary fibrosis via biliary EMT. Experiments using cultured human biliary epithelial cells revealed that stimulation with poly(I : C) (a synthetic analogue of viral dsRNA) increased the expression of basic fibroblast growth factor (bFGF, an EMT‐inducer), S100A4 (a mesenchymal marker) and Snail (a transcriptional factor), and decreased that of epithelial markers (biliary‐type cytokeratin 19 and E‐cadherin) and Bambi (TGF‐β1 pseudoreceptor). The expression of TGF‐β1 (EMT‐inducer) and vimentin (a mesenchymal marker) was not affected by poly(I : C). Both EMT‐inducers, bFGF and TGF‐β1, evoked a decrease and increase in the expression of the epithelial markers and of vimentin respectively, and the expression of Bambi was down‐regulated on stimulation with bFGF. Combined treatment with bFGF and TGF‐β1 quickly and completely induced a transformation of morphology as well as change from epithelial to mesenchymal features in cultured biliary epithelial cells. Immunohistochemistry revealed that biliary epithelial cells lining extrahepatic bile ducts and peribiliary glands in BA frequently show a lack of epithelial markers and an aberrant expression of vimentin. Moreover, the biliary epithelium showing sclerosing cholangitis expressed bFGF accompanied by bFGF‐positive mononuclear cells. In conclusion, the EMT may contribute to the histogenesis of sclerosing cholangiopathy, and the biliary innate immune response to dsRNA viruses induces biliary epithelial cells to undergo EMT via the production of bFGF and the increased susceptibility to TGF‐β1 caused by the down‐regulation of Bambi expression. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Over‐expression of metallothionein predicts chemoresistance in breast cancer
Authors: Yap Xinli , Tan Hong‐Yong , Huang Jingxiang , Lai Yiyang , Yip George Wai‐Cheong , Tan Puay‐Hoon , Bay Boon‐Huat 
Published: November 2008

AbstractMetallothionein (MT) plays a role in fundamental cellular processes such as proliferation, apoptosis and differentiation. We examined MT expression in women with invasive breast ductal carcinoma who underwent mastectomy/lumpectomy without neo‐adjuvant treatment. We showed that MT was over‐expressed in 87.9% of breast cancer tissues examined, with the mean percentage of positive cells at 30%. There were two patterns of MT expression: predominantly cytoplasmic in 75.9% and nuclear in 24.1% of MT‐positive cases. Higher MT scores were associated with poorer histological grade (p = 0.009) but were independent of age, tumour size and oestrogen receptor status. For patients who were treated with adjuvant chemotherapy (cyclophosphamide/methotrexate/5 fluorouracil‐ or doxorubicin‐based regimes), those with high MT expression had a significantly lower recurrence‐free survival (p = 0.048), suggesting a role of MT in predicting disease recurrence. Down‐regulation of MT in MCF‐7 cells by silencing the MT‐2A gene (the most abundantly expressed of the 10 known functional MT isoforms) increased chemosensitivity of the cells to doxorubicin. To examine the mechanisms underlying these clinical data, we used siRNAs to decrease MT‐2A mRNA expression and protein expression. In MT down‐regulated cells challenged with the IC50 concentration of doxorubicin, we observed a significant reduction in cell viability. Cell cycle analysis also revealed a corresponding increase in apoptosis in the MT down‐regulated cells following doxorubicin exposure, showing that down‐regulation of MT increased susceptibility to doxorubicin cytotoxicity. The data suggest that MT could be a potential marker of chemoresistance and a molecular therapeutic target. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Defective activations of STAT3 Ser727 and PKC isoforms lead to oncostatin M resistance in metastatic melanoma cells
Authors: Lacreusette A. , Barbieux Isabelle , Nguyen Jean‐Michel , Pandolfino Marie‐Christine , Dréno Brigitte , Jacques Yannick , Godard Anne , Blanchard Frédéric 
Published: November 2008

AbstractStage III melanoma is refractory to common therapies and shows resistance to the anti‐proliferative activity of cytokines in vitro. We previously demonstrated that, for 30% of the metastatic melanoma cell lines, oncostatin M (OSM) resistance is due to the epigenetic silencing of its receptor OSMRβ. Here we analyse, on a larger panel of short‐term cultures derived from melanoma‐invaded lymph nodes, other mechanisms potentially implicated in OSM resistance. For 18% of the cell lines, OSM resistance is associated with a phosphorylation defect of signal transducer and activator of transcription (STAT)3 on serine (Ser)727, in concordance with defects in the activation of various protein kinase C (PKC) isoforms, especially PKCδ. For 21% of the cell lines, OSM resistance is associated with a defect in the activation of Akt on Ser473. By the use of inhibitors, dominant negatives and small interfering (si)RNA, we show that the PKC–STAT3 Ser727, but not the Akt, pathway appears necessary for OSM anti‐proliferative activity. Moreover, we bring evidence that OSM or interleukin (IL)‐6, produced in lymph nodes and/or melanoma cells, could be involved in the establishment of OSM resistance during melanoma progression. These findings could be relevant for the prognosis and the treatment of stage III melanoma patients. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Induction of anti‐tumour immunity by dendritic cells transduced with hTERT recombinant adenovirus in mice
Authors: Chen Ling , Tang Xu‐Dong , Yu Song‐Tao , Ai Zhi‐Hua , Fang Dian‐Chun , Cai Yong‐Guo , Luo Yuan‐Hui , Liang Guang‐Ping , Yang Shi‐Ming 
Published: November 2008

AbstractDendritic cells (DCs) transfected with recombinant, replication‐defective adenovirus (Ad) vectors encoding the human telomerase reverse transcriptase (hTERT) are potent inducers of cytotoxic T lymphocytes (CTLs) and anti‐tumour immunity. However, previous studies have mostly been in vitro. In this study, we sought to determine whether DCs transfected with hTERT (DC/Ad‐hTERT) could elicit a potent anti‐tumour immunogenic response in vivo. We found that murine DCs transfected with recombinant adenovirus encoding the hTERT gene (DC/Ad‐hTERT) induced hTERT‐specific CTLs in vivo effectively, compared with Ad‐LacZ‐transduced DC (DC/Ad‐LacZ) controls. These hTERT‐specific CTLs lysed various tumour cell lines in an hTERT‐specific and MHC‐I molecule‐restricted fashion. We also found that DC/Ad‐hTERT could increase antigen‐specific T‐cell proliferation and augment the number of IFN‐γ secreting T‐cells in mice. These data suggest that the DC/Ad‐hTERT vaccine may induce anti‐tumour immunity against tumour cells expressing hTERT in an MHC‐I molecule‐restricted fashion in vivo through the augmentation of the hTERT‐specific CTL response. The DC/Ad‐hTERT vaccine may thus be used as an efficient DC‐based tumour vaccine in clinical applications. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Germline and somatic NF1 mutations in sporadic and NF1‐associated malignant peripheral nerve sheath tumours
Authors: Bottillo Irene , Ahlquist Terje , Brekke Helge , Danielsen Stine A , van den Berg Eva , Mertens Fredrik , Lothe Ragnhild A , Dallapiccola Bruno 
Published: November 2008

AbstractMalignant peripheral nerve sheath tumours (MPNSTs) are a malignancy occurring with increased frequency in patients with neurofibromatosis type 1 (NF1). In contrast to the well‐known spectrum of germline NF1 mutations, the information on somatic mutations in MPNSTs is limited. In this study, we screened NF1, KRAS, and BRAF in 47 MPNSTs from patients with (n = 25) and without (n = 22) NF1. In addition, DNA from peripheral blood and cutaneous neurofibroma biopsies from, respectively, 14/25 and 7/25 of the NF1 patients were analysed. Germline NF1 mutations were detected in ten NF1 patients, including three frameshift, three nonsense, one missense, one splicing alteration, and two large deletions. Somatic NF1 mutations were found in 10/25 (40%) NF1‐associated MPNSTs, in 3/7 (43%) neurofibromas, and in 9/22 (41%) sporadic MPNSTs. Large genomic copy number changes accounted for 6/10 and 7/13 somatic mutations in NF1‐associated and sporadic MPNSTs, respectively. Two NF1‐associated and 13 sporadic MPNSTs did not show any NF1 mutation. A major role of the KRAS and BRAF genes was ruled out. The spectrum of germline NF1 mutations in neurofibromatosis patients with MPNST is different from the spectrum of somatic mutations seen in MPNSTs. However, the somatic events share common characteristics with the NF1‐related and the sporadic tumours. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
First trimester maternal serum PAPP‐A, β‐hCG and ADAM12 in prediction of small‐for‐gestational‐age fetuses
Authors: Pihl Kasper , Larsen Torben , Krebs Lone , Christiansen Michael 
Published: November 2008

AbstractObjectiveTo examine the ability of predicting fetuses being small‐for‐gestational‐age (SGA) at delivery with the maternal serum markers pregnancy‐associated plasma protein A (PAPP‐A), beta‐human chorionic gonadotrophin (β‐hCG) and A disintegrin and metalloprotease 12 (ADAM12) in first trimester.MethodsIn all,36 cases being SGA (birth weight < 5th centile) and 108 controls being non‐SGA were matched on ethnicity (only Caucasians), smoking status (only nonsmokers), body mass index (BMI), age and parity. Stored blood samples from PAPP‐A and β‐hCG testing obtained at gestational age (GA) of 8 weeks to 13 weeks and 6 days were analyzed for ADAM12. Median MoM values were compared using Mann‐Whitney test. Monte Carlo estimation and receiver‐operator‐characteristics curves were used to asses screening performance.ResultsMedian MoM values of PAPP‐A (0.64 vs 1.02, p < 0.001), β‐hCG (0.74 vs 1.04, p = 0.007) and ADAM12 (0.74 vs 0.97, p = 0.004) were significantly reduced in cases compared to controls. The combination of PAPP‐A MoM and β‐hCG MoM yielded a detection rate (DR) for SGA of 26% for a 5% false‐positive rate (FPR). Addition of ADAM12 only improved (28% DR for a 5% FPR) screening performance modestly.ConclusionEarly prediction of fetuses being SGA is feasible with the combination of first trimester PAPP‐A, β‐hCG and ADAM12. Screening performance is approaching clinical relevance. The inclusion of further markers is an attractive option. Copyright © 2008 John Wiley & Sons, Ltd.
Effects of participation in a martial arts–based antibullying program in elementary schools
Authors: Twemlow Stuart W. , Biggs Bridget K. , Nelson Timothy D. , Vernberg Eric M. , Fonagy Peter , Twemlow Stephen W. 
Published: November 2008

AbstractThis study evaluated the Gentle Warrior Program, a traditional martial arts–based intervention to reduce aggression in children, as it was implemented in three elementary schools. The sample consisted of 254 children in grades 3, 4, and 5 who participated in the Gentle Warrior Program as part of a larger school violence intervention. Results indicated that boys who participated in more Gentle Warrior sessions reported a lower frequency of aggression and greater frequency of helpful bystanding (i.e., helpful behavior toward victims of bullying) over time, relative to boys with less frequent participation. The effect of participation on aggression was partially mediated by empathy. The effect of participation on helpful bystanding was fully mediated by changes in student empathy. No significant results were found for girls. Results of the study provide preliminary support for the use of martial arts–based interventions to address bullying in schools for boys, by teaching empathy, self‐control, and peaceful strategies to resolve conflicts. © 2008 Wiley Periodicals, Inc.
The relationship between, and treatment of, DSM Axis I and II disorders encountered in combination
Authors: Stevenson Janine , Boyce Philip , Brodaty Henry 
Published: November 2008

AbstractMuch has been written about the comorbidity of Diagnostic and Statistical Manual of Mental Disorders (DSM) Axis I and II disorders in psychiatry. The presence of an Axis II disorder is said to have a negative effect on the symptomatology, treatment and outcome of Axis I disorders. In this paper, we discuss the interrelationship between Axis I and II disorders, between heredity and environment, and between temperament and personality. The clinical utility of the DSM system is challenged. The clinical example used illustrates the difficulty in distinguishing social phobia from avoidant personality disorder in a person also ‘comorbid’ for borderline personality disorder and anorexia nervosa. Biological and dynamic aetiologies are considered in the development of this complex constellation of symptomatology, whether there are indeed multiple disorders in the one person or the symptoms are an expression of a common aetiology. Psychotherapeutic and pharmacotherapeutic treatments are discussed. Copyright © 2008 John Wiley & Sons, Ltd.
Gel‐based proteomics of Gram‐positive bacteria: A powerful tool to address physiological questions
Authors: Hecker Michael , Antelmann Haike , Büttner Knut , Bernhardt Jörg 
Published: November 2008

AbstractIn this review, we demonstrate the power of gel‐based proteomics to address physiological questions of bacteria. Although gel‐based proteomics covers a subpopulation of proteins only, fundamental issues of a bacterial cell such as almost all metabolic pathways or the main signatures of stress and starvation responses can be analyzed. The analysis of the synthesis pattern of single proteins, e.g., in response to environmental changes, requires gel‐based proteomics because only this technique can compare protein synthesis and amount in the same 2‐D gel. Moreover, highly sophisticated software packages facilitate the analysis of the regulation of the main metabolic enzymes or the stress/starvation responses, PTMs, protein damage/repair, and degradation and finally protein secretion mechanisms at a proteome‐wide scale. The challenge of proteomics whose panorama view shows events never seen before is to select the most interesting issues for detailed follow up studies. This “road map of proteomics” from proteome data via new hypothesis and finally novel molecular mechanisms should lead to exciting information on bacterial physiology. However, many proteins escape detection by gel‐based procedures, such as membrane or low abundance proteins. The smart combination of gel‐free and gel‐based approaches is the “state of the art” for physiological proteomics of bacteria.
Omics‐based profiling of carcinoma of the breast and matched regional lymph node metastasis
Authors: Li Jian , Gromov Pavel , Gromova Irina , Moreira José M. , Timmermans‐Wielenga Vera , Rank Fritz , Wang Kai , Li Shengting , Li Heng , Wiuf Carsten , Yang Huanming , Zhang Xiuqing , Bolund Lars , Celis Julio E. 
Published: November 2008

AbstractAxillary lymph node (ALN) status is currently used as an important clinical indicator of breast cancer prognosis. However, the molecular mechanisms underlying lymph node metastasis are poorly understood and the relationship between ALN metastasis and the primary tumor remains unclear. In an effort to reveal structural changes in the genome and related protein responses that may drive regional metastatic progression we have analyzed matched pairs of primary breast tumors and ALN metastases both at the genomic and proteomic levels using comparative genomic hybridization (CGH) array, quantitative high‐resolution 2‐D PAGE in combination with MS, and immunohistochemistry (IHC). Array CGH revealed a remarkable similarity in genomic aberration profiles between the matched primary tumors and the ALN metastases. Quantitative profiling of 135 known proteins also revealed striking similarities in their overall expression patterns, although we observed distinct changes in the levels of individual proteins in some sample pairs. The remarkable similarities of the overall genomic and proteomic profiles between primary tumors and matched ALN metastases are taken to suggest that, in general, key biological characteristics of the primary breast tumor are maintained in the corresponding lymph node metastases. Given that the omics‐based technologies are oblivious to changes that only occur in minor cellular subsets we validated the proteomic data using IHC, which provides protein expression information with a valuable topological component. Besides confirming the omics‐derived data, the IHC analysis revealed that in two cases the ALN metastases may have been derived from a distinct minor cell subpopulation present in the primary tumor rather than from the bulk of it.
Spin‐controlled optoelectronic devices
Authors: Hövel S. , Gerhardt N. C. , Hofmann M. R. , Lo F.‐Y. , Reuter D. , Wieck A. D. , Schuster E. , Wende H. , Keune W. 
Published: November 2008

AbstractWe report on novel spin‐optoelectronic devices which may transfer spintronics from the lab towards practical applications. Efficient spin‐injection into light emitting diodes is provided by tunnelling through a MgO‐barrier both at room temperature and without magnetic fields due to a special Fe/Tb‐injector architecture. Furthermore, we show spin‐amplification in lasers and finally a robust back conversion of polarised light into a spin‐current by spin‐filtering in a spin‐detector, both working at room temperature. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Benefits of negative polarization charge in n ‐InGaN on p ‐GaN single heterostructure light emitting diode with p ‐side down
Authors: Reed M. L. , Readinger E. D. , Moe C. G. , Shen H. , Wraback M. , Syrkin A. , Usikov A. , Kovalenkov O. V. , Dmitriev V. A. 
Published: November 2008

AbstractThe effects of negative polarization charge at the n ‐InGaN/p ‐GaN interface on the performance of hydride vapour phase epitaxy‐deposited single heterostructure n ‐In0.17Ga0.83N/p ‐GaN light emitting diodes with p ‐side down are investigated. The negative polarization charge at the interface leads to the formation of a two‐dimensional hole gas within the InGaN near the n ‐InGaN/p ‐GaN interface, as well as reducing the barrier for hole injection. In addition, electrons encounter experience a significant barrier for injection across the heterointerface. As a result, superlinear increase in light output as injection current increases below 20 A/cm2 and peak emission wavelength shift from 495 nm to 470 nm are observed. We show that the combination of two‐dimensional hole‐gas formation on the n ‐InGaN side of the hetero‐interface and enhancement of the electron barrier to transport across this interface may reduce efficiency droop at high current density without the need for an AlGaN electron blocking layer. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Oxide‐mediated formation of α‐FeSi2 on Si(001) studied by X‐ray adsorption near edge structure analysis using SPELEEM
Authors: Maeda Fumihiko , Hibino Hiroki , Suzuki Satoru , Guo Fang Zhun 
Published: November 2008

AbstractTo investigate the effect of the oxide layer on the oxide‐mediated growth in solid phase epitaxy for the formation of a single‐phase iron disilicides, the annealing processes were analyzed using spectroscopic photoemission and low‐energy electron microscopy for a special surface where oxide areas and clean substrate areas (voids) coexist closely in a micrometer‐order view. From the analysis of high‐resolution X‐ray adsorption near edge structure (XANES), we found that a pure α phase of FeSi2 was obtained in the oxide area after annealing at 720 °C, although a mixture of its α and β phases was obtained in the void area. This indicates that the oxide layer effectively worked and a single‐phase α‐FeSi2 was successfully formed by the oxide‐mediated growth. Copyright © 2008 John Wiley & Sons, Ltd.
Electroless plating of copper on Si(100) surfaces modified by surface‐initiated atom‐transfer radical polymerization of 4‐vinylpyridine
Authors: Li Liang , Yan Guoping , Cheng Zhiyu , Wu Jiangyu , Yu Xianghua , Guo Qingzhong 
Published: November 2008

AbstractSurface‐initiated atom‐transfer radical polymerization (ATRP) of 4‐vinylpyridine (4VP) on a pretreated Si(100) surface was carried out. The composition and topography of the Si(100) surface modified by poly(4‐vinylpyridine) (P4VP) were characterized by XPS and atomic force microscopy (AFM), respectively. The P4VP layer on the Si(100) surface was used not only as chemisorption sites for the palladium complexes without prior sensitization by SnCl2 solution during the electroless plating, but also as an adhesion promotion layer for the electrolessly deposited copper. The electrolessly deposited copper on the Si–P4VP surface exhibited a 180° peel adhesion strength above 6 N/cm. The adhesion strength was much higher than that of the electrolessly deposited copper to the pristine silicon surface. Copyright © 2008 John Wiley & Sons, Ltd.
With greater power comes greater responsibility? takeover protection and corporate attention to stakeholders
Authors: Kacperczyk Aleksandra 
Published: November 2008

AbstractUsing takeover protection as an indicator of corporate governance, this study examines how an exogenous shift in power from shareholders to managers affects corporate attention to non‐shareholding stakeholders. Two competing hypotheses are entertained. The shareholder view predicts that stronger takeover protection will lead to a decrease in corporate attention to shareholders and non‐shareholding stakeholders alike, as managers divert resources from shareholders to the pursuit of their private interests. The stakeholder view, in contrast, predicts that stronger takeover protection will increase corporate attention to non‐shareholding stakeholders. Because catering to non‐shareholding stakeholders contributes to the long‐term value of the firm, managers will be more likely to attend to those stakeholders when relieved from short‐termism triggered by the threat of hostile takeovers. Using a sample of 878 U.S. firms from 1991 to 2002, the study finds that an exogenous increase in takeover protection leads to higher corporate attention to community and the natural environment, but has no impact on corporate attention to employees, minorities, and customers. Additional analyses show that firms that increase their attention to stakeholders experience an increase in long‐term shareholder value. These findings provide additional evidence that relief from short‐termism is a likely source of the increase in corporate attention to non‐shareholding stakeholders following the increase in takeover protection. Copyright © 2008 John Wiley & Sons, Ltd.