bluuebunny/crossref_metadata_2025_split huggingface dataset:
HuR Knockdown Changes the Oncogenic Potential of Oral Cancer Cells
Authors: Kakuguchi Wataru , Kitamura Tetsuya , Kuroshima Takeshi , Ishikawa Makoto , Kitagawa Yoshimasa , Totsuka Yasunori , Shindoh Masanobu , Higashino Fumihiro 
Published: March 2010

Abstract
HuR binds to AU-rich element–containing mRNA to protect them from rapid degradation. Here, we show that knockdown of HuR changes the oncogenic properties of oral cancer cells. Oral squamous cell carcinoma cell lines, HSC-3 and Ca9.22, which express HuR protein and cytoplasmic AU-rich element mRNA more abundantly than normal cells, were subjected to HuR knockdown. In the HuR-knockdown cancer cells, the cytoplasmic expression of c-fos, c-myc, and COX-2 mRNAs was inhibited compared with those in cells that had been transfected with a control small interfering RNA, and the half-lives of these mRNAs were shorter than those of their counterparts in the control cells. HuR-knockdown cells failed to make colonies in soft agar, suggesting that the cells had lost their ability for anchorage-independent cell growth. Additionally, the motile and invasive activities of the cells decreased remarkably by HuR knockdown. Furthermore, the expression of cell cycle–related proteins, such as cyclin A, cyclin B1, cyclin D1, and cyclin-dependent kinase 1, was reduced in HuR-knockdown cancer cells, and HuR bound to cdk1 mRNA to stabilize it. These findings suggest that HuR knockdown changes the features of oral cancer cells, at least in part, by affecting their cell cycle and shows potential as an effective therapeutic approach. Mol Cancer Res; 8(4); 520–8. ©2010 AACR.
Interleukin-1R–Associated Kinase 2 Is a Novel Modulator of the Transforming Growth Factor β Signaling Cascade
Authors: Mullenders Jasper , Fabius Armida W.M. , van Dongen Miranda M.W. , Kuiken Hendrik J. , Beijersbergen Roderick L. , Bernards René 
Published: March 2010

Abstract
The transforming growth factor β (TGFβ) pathway orchestrates an extensive transcriptional program that is important for many processes in the cell. For example, TGFβ regulates cell cycle, migration, and epithelial-to-mesenchymal transition. The TGFβ pathway has a dual role in cancer: it is involved in early-stage tumor suppression but also contributes to tumor progression by promoting invasion. To identify the novel genes involved in TGFβ pathway signaling, we have performed a functional genetic loss-of-function screen. We screened a small interfering RNA library targeting 700 kinases and kinase-related genes in a TGFβ-responsive reporter assay. Several genes were identified that upon knockdown could repress the reporter signal; among these are the two cellular receptors for TGFβ. In addition to these two known components of the TGFβ pathway, several genes were identified that were previously not linked to the TGFβ signaling. Knockdown of one of these genes, the IRAK2 kinase, resulted not only in an impaired TGFβ target gene response but also in a reduction of the nuclear accumulation and phosphorylation of SMAD2. In addition, suppression of interleukin-1R–associated kinase 2 expression led to a partial override of a TGFβ-induced cell cycle arrest. Our data show that interleukin-1R–associated kinase 2 is a novel and critical component of TGFβ signaling. Mol Cancer Res; 8(4); 592–603. ©2010 AACR.
Resveratrol Suppresses Colitis and Colon Cancer Associated with Colitis
Authors: Cui Xiangli , Jin Yu , Hofseth Anne B. , Pena Edsel , Habiger Joshua , Chumanevich Alexander , Poudyal Deepak , Nagarkatti Mitzi , Nagarkatti Prakash S. , Singh Udai P. , Hofseth Lorne J. 
Published: March 2010

AbstractResveratrol is a naturally occurring polyphenol that exhibits pleiotropic health beneficial effects, including anti-inflammatory, cardio-protective, and cancer-protective activities. It is recognized as one of the more promising natural molecules in the prevention and treatment of chronic inflammatory and autoimmune disorders. Ulcerative colitis is an idiopathic, chronic inflammatory disease of the colon associated with a high colon cancer risk. Here, we used a dextran sulfate sodium (DSS) mouse model of colitis, which resembles human ulcerative colitis pathology. Resveratrol mixed in food ameliorates DSS-induced colitis in mice in a dose-dependent manner. Resveratrol significantly improves inflammation score, downregulates the percentage of neutrophils in the mesenteric lymph nodes and lamina propria, and modulates CD3+ T cells that express tumor necrosis factor-α and IFN-γ. Markers of inflammation and inflammatory stress (p53 and p53-phospho-Ser15) are also downregulated by resveratrol. Because chronic colitis drives colon cancer risk, we carried out experiments to determine the chemopreventive properties of resveratrol. Tumor incidence is reduced from 80% in mice treated with azoxymethane (AOM) + DSS to 20% in mice treated with AOM + DSS + resveratrol (300 ppm). Tumor multiplicity also decreased with resveratrol treatment. AOM + DSS–treated mice had 2.4 ± 0.7 tumors per animal compared with AOM + DSS + 300 ppm resveratrol, which had 0.2 ± 0.13 tumors per animal. The current study indicates that resveratrol is a useful, nontoxic complementary and alternative strategy to abate colitis and potentially colon cancer associated with colitis. Cancer Prev Res; 3(4); 549–59. ©2010 AACR.
Interphase Cytogenetics of Sputum Cells for the Early Detection of Lung Carcinogenesis
Authors: Prindiville Sheila A. , Ried Thomas 
Published: March 2010

Abstract
This perspective on Varella-Garcia et al. (beginning on p. 447 in this issue of the journal) examines the role of interphase fluorescence in situ hybridization for the early detection of lung cancer. This work is an important step toward identifying and validating a molecular marker in sputum samples for lung cancer early detection and highlights the value of establishing cohort studies with biorepositories of samples collected from participants followed over time for disease development. Cancer Prev Res; 3(4); 416–9. ©2010 AACR.
Lung Cancer Biomarkers: FISHing in the Sputum for Risk Assessment and Early Detection
Authors: Gomperts Brigitte N. , Spira Avrum , Elashoff David E. , Dubinett Steven M. 
Published: March 2010

AbstractThis perspective on Varella-Garcia et al. (beginning on p. 447 in this issue of the journal) discusses the role of sputum-based biomarkers in the risk assessment and early detection of lung cancer. The importance of the detection of sputum epithelial chromosomal aneusomy by fluorescence in situ hybridization (FISH) as a potential risk or early-detection biomarker is discussed in the context of other biomarkers and models in lung carcinogenesis. The presently reported findings on FISH in sputum cells are an important contribution worthy of further investigation in defined clinical settings. Cancer Prev Res; 3(4); 420–3. ©2010 AACR.
Long-Term Outcome of Alcohol Septal Ablation in Patients With Obstructive Hypertrophic Cardiomyopathy
Authors: ten Cate Folkert J. , Soliman Osama I.I. , Michels Michelle , Theuns Dominic A.M.J. , de Jong Peter L. , Geleijnse Marcel L. , Serruys Patrick W. 
Published: March 2010

Background—
The impact of alcohol septal ablation (ASA)-induced scar is not known. This study sought to examine the long-term outcome of ASA among patients with obstructive hypertrophic cardiomyopathy.

Methods and Results—

Ninety-one consecutive patients (aged 54±15 years) with obstructive hypertrophic cardiomyopathy underwent ASA. Primary study end point was a composite of cardiac death and aborted sudden cardiac death including appropriate cardioverter-defibrillator discharges for fast ventricular tachycardia/ventricular fibrillation. Secondary end points were noncardiac death and other nonfatal complications. Outcomes of ASA patients were compared with 40 patients with hypertrophic cardiomyopathy who underwent septal myectomy. During 5.4±2.5 years, primary and/or secondary end points were seen in 35 (38%) ASA patients of whom 19 (21%) patients met the primary end point. The 1-, 5-, and 8-year survival-free from the primary end point was 96%, 86%, and 67%, respectively in ASA patients versus 100%, 96%, and 96%, respectively in myectomy patients during 6.6±2.7 years (log-rank,
P
=0.01). ASA patients had a ≈5-fold increase in the estimated annual primary end point rate (4.4% versus 0.9%) compared with myectomy patients. In a multivariable model including a propensity score, ASA was an independent predictor of the primary end point (unadjusted hazard ratio, 5.2; 95% CI, 1.2 to 22.1;
P
=0.02 and propensity score-adjusted hazard ratio, 6.1; 95% CI, 1.4 to 27.1;
P
=0.02).

Conclusions—
This study shows that ASA has potentially unwanted long-term effects. This poses special precaution, given the fact that ASA is practiced worldwide at increasing rate. We recommend myectomy as the preferred intervention in patients with obstructive hypertrophic cardiomyopathy.
Enacted Destiny:West African Charismatic Christians in Berlin and the Immanence of God
Authors: Nieswand Boris 
Published: March 2010

AbstractThe focus of this article is the concept of enacted destiny, which was identified among charismatic Christians of West African origin in Berlin. Different from more fatalistic concepts of destiny, it combines a strong notion of free agency with a strong notion of a good, almighty, and immanent God. The imaginary of enacted destiny is constituted by two components: 1. presituational religious empowerment by which charismatic Christians can reduce complexities, anxieties, and insecurities in the context of decision making; and 2. postsituational sense-making by which divine agency is ascribed to an originally ambiguous situation. Both components temporally embrace the actions of West African charismatic Christians in Berlin. Actions thereby become the means through which God becomes immanent in the everyday lives of West African charismatic Christians in Berlin and enacted destiny a category of movement toward convergence of human and divine agency.
Protecting the Best Interests of the Child: A Comparative Analysis of the Youth Justice Systems in Ireland, England and Scotland
Authors: Arthur Raymond 
Published: March 2010

AbstractIn the Republic of Ireland the government has proposed amending the Irish Constitution in order to improve children's rights. In this article I will argue that the proposed amendment represents a serious diminution in the rights historically afforded to young people who offend, disregards Ireland's commitments under international law and also ignores the well established link between child maltreatment and youth offending. The Irish approach echoes developments in the English youth justice system where the welfare concerns of young people who offend have become marginalised. I will compare the Irish and English approaches with the Scottish youth justice system which looks beyond young people's offending behaviour and provides a multi-disciplinary assessment of the young person's welfare needs. I will conclude that in Ireland, and in England, the best interest principle must be applied fully, without any distinction and integrated in all law relevant to children including laws regulating anti-social and offending behaviour.
A Cumulus Parameterization with State-Dependent Entrainment Rate. Part II: Impact on Climatology in a General Circulation Model
Authors: Chikira Minoru 
Published: March 2010

Abstract
The impact of a new cumulus parameterization developed in Part I of this paper on climatology in an atmospheric general circulation model (AGCM) is compared with that of the Arakawa–Schubert scheme. The parameterization is characterized by a vertically variable entrainment rate depending on the surrounding environment. Two kinds of formulations on entrainment rate are tested and produce similar results in the AGCM. The results show reduction of precipitation over land and increase over the sea, weakening of the southern side of the double intertropical convergence zone (ITCZ) over the southeastern Pacific, and better representation of the South Pacific convergence zone (SPCZ), all of which are consistent with observations. The population of cumulus congestus is significantly increased, thereby inducing additional heating in the lower troposphere. The diurnal variation over land shows that deep convection tends to be suppressed earlier because of the reduction of convective available potential energy and tropospheric humidity caused by the convective activity itself. An analysis of the daily outputs suggests that a better representation of the cumulus congestus and sensitivity of the scheme to tropospheric humidity are important for the realistic representation of the precipitation over the double ITCZ and SPCZ.
Intensification of Summer Rainfall Variability in the Southeastern United States during Recent Decades
Authors: Wang Hui , Fu Rong , Kumar Arun , Li Wenhong 
Published: March 2010

Abstract
The variability of summer precipitation in the southeastern United States is examined in this study using 60-yr (1948–2007) rainfall data. The Southeast summer rainfalls exhibited higher interannual variability with more intense summer droughts and anomalous wetness in the recent 30 years (1978–2007) than in the prior 30 years (1948–77). Such intensification of summer rainfall variability was consistent with a decrease of light (0.1–1 mm day−1) and medium (1–10 mm day−1) rainfall events during extremely dry summers and an increase of heavy (&gt;10 mm day−1) rainfall events in extremely wet summers. Changes in rainfall variability were also accompanied by a southward shift of the region of maximum zonal wind variability at the jet stream level in the latter period. The covariability between the Southeast summer precipitation and sea surface temperatures (SSTs) is also analyzed using the singular value decomposition (SVD) method. It is shown that the increase of Southeast summer precipitation variability is primarily associated with a higher SST variability across the equatorial Atlantic and also SST warming in the Atlantic.
Observed and Projected Future Shifts of Climatic Zones in Europe and Their Use to Visualize Climate Change Information
Authors: Jylhä Kirsti , Tuomenvirta Heikki , Ruosteenoja Kimmo , Niemi-Hugaerts Hanna , Keisu Krista , Karhu Juha A. 
Published: March 2010

AbstractA Web site questionnaire survey in Finland suggested that maps illustrating projected shifts of Köppen climatic zones are an effective visualization tool for disseminating climate change information. The climate classification is based on seasonal cycles of monthly-mean temperature and precipitation, and it divides Europe and its adjacent land areas into tundra, boreal, temperate, and dry climate types. Projections of future changes in the climatic zones were composed using multimodel mean projections based on simulations performed with 19 global climate models. The projections imply that, depending on the greenhouse gas scenarios, about half or possibly even two-thirds of the study domain will be affected by shifts toward a warmer or drier climate type during this century. The projected changes within the next few decades are chiefly located near regions where shifts in the borders of the zones have already occurred during the period 1950–2006. The questionnaire survey indicated that the information regarding the shifting climatic zones as disseminated by the maps was generally interpreted correctly, with the average percentage of correct answers being 86%. Additional examples of the use of the climatic zones to communicate climate change information to the public are included.
Spleen tyrosine kinase inhibition prevents chemokine- and integrin-mediated stromal protective effects in chronic lymphocytic leukemia
Authors: Buchner Maike , Baer Constance , Prinz Gabriele , Dierks Christine , Burger Meike , Zenz Thorsten , Stilgenbauer Stephan , Jumaa Hassan , Veelken Hendrik , Zirlik Katja 
Published: March 2010

AbstractThe microenvironment provides essential growth and survival signals to chronic lymphocytic leukemia (CLL) cells and contributes to their resistance to cytotoxic agents. Pharmacologic inhibition of spleen tyrosine kinase (SYK), a key mediator of B-cell receptor (BCR) signaling, induces apoptosis in primary CLL cells and prevents stroma contact-mediated cell survival. This report demonstrates a role of SYK in molecularly defined pathways that mediate the CLL-microenvironmental crosstalk independent from the BCR. Chemokine and integrin stimulation induced SYK phosphorylation, SYK-dependent Akt phosphorylation, and F-actin formation in primary CLL cells. Inhibition of SYK by 2 pharmacologic inhibitors and siRNA-knockdown abrogated downstream SYK signaling and morphologic changes induced by these stimuli. CLL cell migration toward CXCL12, the major homing attractor, and CLL cell adhesion to VCAM-1, a major integrin ligand expressed on stromal cells, were markedly reduced by SYK inhibition. In combination with fludarabine, the SYK inhibitor R406 abrogated stroma-mediated drug resistance by preventing up-regulation of the antiapoptotic factor Mcl-1 in CLL cells. SYK blockade in CLL is a promising therapeutic principle not only for its inhibition of the BCR signaling pathway, but also by inhibiting protective stroma signals in a manner entirely independent of BCR signaling.
How I treat common variable immune deficiency
Authors: Cunningham-Rundles Charlotte 
Published: March 2010

AbstractCommon variable immunodeficiency is a rare immune deficiency, characterized by low levels of serum immunoglobulin G, A, and/or M with loss of antibody production. The diagnosis is most commonly made in adults between the ages of 20 and 40 years, but both children and older adults can be found to have this immune defect. The range of clinical manifestations is broad, including acute and chronic infections, inflammatory and autoimmune disease, and an increased incidence of cancer and lymphoma. For all these reasons, the disease phenotype is both heterogeneous and complex. Contributing to the complexity is that patient cohorts are generally small, criteria used for diagnosis vary, and the doses of replacement immune globulin differ. In addition, routines for monitoring patients over the years and protocols for the use of other biologic agents for complications have not been clarified or standardized. In the past few years, data from large patient registries have revealed that both selected laboratory markers and clinical phenotyping may aid in dissecting groups of subjects into biologically relevant categories. This review presents my approach to the diagnosis and treatment of patients with common variable immunodeficiency, with suggestions for the use of laboratory biomarkers and means of monitoring patients.
The association of reduced folate carrier 80G>A polymorphism to outcome in childhood acute lymphoblastic leukemia interacts with chromosome 21 copy number
Authors: Gregers Jannie , Christensen Ib Jarle , Dalhoff Kim , Lausen Birgitte , Schroeder Henrik , Rosthoej Steen , Carlsen Niels , Schmiegelow Kjeld , Peterson Curt 
Published: March 2010

Abstract
The reduced folate carrier (RFC) is involved in the transport of methotrexate (MTX) across the cell membrane. The RFC gene (SLC19A1) is located on chromosome 21, and we hypothesized that the RFC80 G>A polymorphism would affect outcome and toxicity in childhood leukemia and that this could interact with chromosome 21 copy number in the leukemic clone. A total of 500 children with acute lymphoblastic leukemia treated according to the common Nordic treatment protocols were included, and we found that the RFC AA variant was associated with a 50% better chance of staying in remission compared with GG or GA variants (P = .046). Increased copy numbers of chromosome 21 appear to improve outcome also in children with GA or GG variant. In a subset of 182 children receiving 608 high-dose MTX courses, we observed higher degree of bone marrow toxicity in patients with the RFC AA variant compared with GA/GG variants (platelet 73 vs 99/105 × 109/L, P = .004, hemoglobin 5.6 vs 5.9/6.0 mmol/L, P = .004) and a higher degree of liver toxicity in patients with RFC GG variant (alanine aminotransferase 167 vs 127/124 U/L, P = .05). In conclusion, the RFC 80G>A polymorphism interacts with chromosome 21 copy numbers and affects both efficacy and toxicity of MTX.
Reciprocal regulation of metabolic and signaling pathways
Authors: Barth Andreas S , Kumordzie Ami , Colantuoni Carlo , Margulies Kenneth B , Cappola Thomas P , Tomaselli Gordon F 
Published: March 2010

Abstract

Background
By studying genome-wide expression patterns in healthy and diseased tissues across a wide range of pathophysiological conditions, DNA microarrays have revealed unique insights into complex diseases. However, the high-dimensionality of microarray data makes interpretation of heterogeneous gene expression studies inherently difficult.

Results
Using a large-scale analysis of more than 40 microarray studies encompassing ~2400 mammalian tissue samples, we identified a common theme across heterogeneous microarray studies evident by a robust genome-wide inverse regulation of metabolic and cell signaling pathways: We found that upregulation of cell signaling pathways was invariably accompanied by downregulation of cell metabolic transcriptional activity (and vice versa). Several findings suggest that this characteristic gene expression pattern represents a new principle of mammalian transcriptional regulation. First, this coordinated transcriptional pattern occurred in a wide variety of physiological and pathophysiological conditions and was identified across all 20 human and animal tissue types examined. Second, the differences in metabolic gene expression predicted the magnitude of differences for signaling and all other pathways, i.e. tissue samples with similar expression levels of metabolic transcripts did not show any differences in gene expression for all other pathways. Third, this transcriptional pattern predicted a profound effect on the proteome, evident by differences in structure, stability and post-translational modifications of proteins belonging to signaling and metabolic pathways, respectively.

Conclusions
Our data suggest that in a wide range of physiological and pathophysiological conditions, gene expression changes exhibit a recurring pattern along a transcriptional axis, characterized by an inverse regulation of major metabolic and cell signaling pathways. Given its widespread occurrence and its predicted effects on protein structure, protein stability and post-translational modifications, we propose a new principle for transcriptional regulation in mammalian biology.