bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variability in the Androgen Response of Prostate Epithelium to 5α-Reductase Inhibition: Implications for Prostate Cancer Chemoprevention
Authors: Mostaghel Elahe A. , Geng Linda , Holcomb Ilona , Coleman Ilsa M. , Lucas Jared , True Lawrence D. , Nelson Peter S. 
Published: February 2010

AbstractInhibitors of 5α-reductase (SRD5A) that lower intraprostatic levels of dihydrotestosterone (DHT) reduce the overall incidence of prostate cancer (PCa), but there is significant variation in chemopreventive activity between individual men. In seeking molecular alterations that might underlie this variation, we compared gene expression patterns in patients with localized PCa who were randomized to prostatectomy alone versus treatment with two different doses of the SRD5A inhibitor dutasteride. Prostatic levels of DHT were decreased by &gt;90% in both dutasteride-treated patient groups versus the untreated patient group. Despite significant and uniform suppression of tissue DHT, unsupervised clustering based on prostatic gene expression did not discriminate these groups. However, subjects could be resolved into distinct cohorts characterized by high or low expression of genes regulated by the androgen receptor (AR), based solely on AR transcript expression. The higher-dose dutasteride treatment group was found to include significantly fewer cancers with TMPRSS2-ERG genetic fusions. Dutasteride treatment was associated with highly variable alterations in benign epithelial gene expression. Segregating subjects based on expression of AR and androgen-regulated genes revealed that patients are differentially sensitive to SRD5A inhibition. Our findings suggest that AR levels may predict the chemopreventive efficacy of SRD5A inhibitors. Cancer Res; 70(4); 1286–95
Vasculogenesis Driven by Bone Marrow-Derived Cells Is Essential for Growth of Ewing's Sarcomas
Authors: Yu Ling , Su Bing , Hollomon Mario , Deng Yong , Facchinetti Valeria , Kleinerman Eugenie S. 
Published: February 2010

Abstract
The role of vasculogenesis as opposed to angiogenesis in tumor formation has been little explored genetically. Endothelial cells that lack the MEK kinase MEKK3 cannot form vessels. In this study, we employed mice with hematopoietic deletions of the Mekk3 gene to evaluate the importance of vasculogenesis in the formation of Ewing's sarcoma tumors. Bone marrow cells (BM) from LacZ+ Mekk3-deficient conditional knockout mice (Mekk3Δflox/− mice) were transplanted into irradiated nude mice before injection of Ewing's sarcoma cells. Because the grafted Mekk3Δflox/− BM cells cannot contribute to vessel development in the same way as the host Mekk3+/+ endothelial cells, angiogenesis is normal in the model whereas vasculogenesis is impaired. Four weeks after BM transplant, Ewing's sarcoma TC71 or A4573 cells were injected, and tumor growth and vessel density were compared. Strikingly, chimeric mice transplanted with Mekk3Δflox/− BM exhibited a reduction in tumor growth and vessel density compared with mice transplanted with Mekk3Δflox/+ BM cells. Mekk3Δflox/− cells that were LacZ positive were visualized within the tumor; however, few of the LacZ+ cells colocalized with either CD31+ endothelial cells or desmin+ pericytes. Quantification of double-positive LacZ+ and CD31+ endothelial cells or LacZ+ and desmin+ pericytes confirmed that chimeric mice transplanted with Mekk3Δflox/− BM were impaired for tumor vessel formation. In contrast, siRNA-mediated knockdown of Mekk3 in TC71 Ewing's sarcoma cells had no effect on tumor growth or vessel density. Our findings indicate that vasculogenesis is critical in the expansion of the tumor vascular network. Cancer Res; 70(4); 1334–43
A MicroRNA Expression Signature for Cervical Cancer Prognosis
Authors: Hu Xiaoxia , Schwarz Julie K. , Lewis James S. , Huettner Phyllis C. , Rader Janet S. , Deasy Joseph O. , Grigsby Perry W. , Wang Xiaowei 
Published: February 2010

Abstract
Invasive cervical cancer is a leading cause of cancer death in women worldwide, resulting in about 300,000 deaths each year. The clinical outcomes of cervical cancer vary significantly and are difficult to predict. Thus, a method to reliably predict disease outcome would be important for individualized therapy by identifying patients with high risk of treatment failures before therapy. In this study, we have identified a microRNA (miRNA)-based signature for the prediction of cervical cancer survival. miRNAs are a newly identified family of small noncoding RNAs that are extensively involved in human cancers. Using an established PCR-based miRNA assay to analyze 102 cervical cancer samples, we identified miR-200a and miR-9 as two miRNAs that could predict patient survival. A logistic regression model was developed based on these two miRNAs and the prognostic value of the model was subsequently validated with independent cervical cancers. Furthermore, functional studies were done to characterize the effect of miRNAs in cervical cancer cells. Our results suggest that both miR-200a and miR-9 could play important regulatory roles in cervical cancer control. In particular, miR-200a is likely to affect the metastatic potential of cervical cancer cells by coordinate suppression of multiple genes controlling cell motility. Cancer Res; 70(4); 1441–8
Competition and International Equity Returns: Some Empirical Tests of “Turbulent Arbitrage”
Authors: Sarich John , Hecht Jason 
Published: February 2010

The idea that capital flows accelerate and decelerate in response to differential rates of return on real investment is common to virtually all of economic theory. This paper examines the nature of this process, especially the relationship between returns in the stock market and returns on real investment. Shaikh (1998) makes the case that the rate of return on new physical (real) investment is the “required” rate of return for the stock market and that competitive forces produce a rough equalization between these two rates of return, what he terms “turbulent arbitrage.” In contrast to neoclassical theories of perfect competition, with its notions of perfect information and convergence to a uniform rate of return, the notion of “turbulent arbitrage” is a dynamic process that requires a tendency toward convergence as well as the constant differentiation of profit rates (Botwinick 1993). Data on rates of return at the country, industry, and firm level for Japan, Germany, the United Kingdom, and the United States are analyzed and correlated with Shaikh’s “incremental rate of return on real investment” which, it is argued, is the target of the equalization process. Statistical and econometric tests based on time series methods and pooling techniques support the hypothesis that the rate of return on equity prices is linked to the incremental return on real investment. In addition, this association is examined for two industries—steel and retail trade—across these same four countries. Global and domestic equity markets are found to be significantly correlated with the incremental returns for the steel industry but not for the retail trade sector. JEL classification: G15, F02, C33
A Tale of Two Thailands: A Minskyan Analysis of Growth in Different Regimes
Authors: Brennan David M. 
Published: February 2010

This paper employs a Kaleckian/Minskyan analysis of profit flows to explain Thailand’s experiences of growth and crisis under different policy regimes. Specifically, the paper shows how profits were differently supported under the neoliberal policy regime of the day and a regime of less stable exchange rates and fiscal deficits. The analysis of the components of profit flows is helpful in explaining why capitalist economies oscillate between different types of monetary and fiscal interventions. JEL classification: F41, E60, E12
The Rise of Knowledge in Dependency Theory: The Experience of India and Taiwan
Authors: Shie Vincent H. , Meer Craig D. 
Published: February 2010

Dependency theorists have been mired in a theoretical impasse since the mid-1980s because they cannot explain the economic achievements of the newly industrializing countries. In the information technology industry, a key sector in the knowledge-based economy, the high-tech industrialization and performance of India and Taiwan are particularly noteworthy. Ironically, however, the rise of knowledge makes these countries more dependent technologically. JEL classification: O34, O53
Democratizing the Classroom: Sequencing Discussions and Assignments to Promote Student Ownership of the Course
Authors: Schneider Geoffrey 
Published: February 2010

This article explores a radical pedagogical method for democratizing the classroom that generates rich, engaged, student-led discussions. The approach is grounded in the notion that democratic participation in the classroom is a worthy goal of radical pedagogy, that students must be adequately prepared in order to take on greater responsibility in the classroom, and that greater learning occurs when students take a more active role in the learning process. Careful sequencing of discussions and assignments is used to turn over responsibility for the course to students gradually, without sacrificing the depth and sophistication that instructors want to achieve in the classroom. The result is a classroom in which all students participate and in which thoughtful, informed discussion and debate is the primary mode of engagement. JEL classification: A22, B5
Technology and journalism-as-labour: Historical perspectives
Authors: Örnebring Henrik 
Published: February 2010

Technological determinism is common among journalists when reflecting on changes in their profession; several studies show that journalists ascribe great power and independent agency to technology. There are at least two reasons for the persistence of technological determinism as an explanatory factor among journalists vis-a-vis their own work: first, technology is a highly integrated and therefore very tangible part of the everyday working life of journalists; and second, the technological paradigm for explaining change in journalism has deep historical roots. It is argued that analysing journalism as labour presents a way to address both the integration of technology in the everyday working practices of journalists, and the history of the inter-relations between journalism and technology. It is further argued that journalism studies as a field has not paid much attention to journalism as labour. This article is concerned with the second part of this programme for research, i.e. the historical analysis of journalism as labour. The framework of analysis is based on labour process theory, focusing on four themes in the history of journalism: (1) the importance of the separation of conception and execution of labour; (2) the increased differentiation of the labour process; (3) the use of technology to increase productivity; and (4) the deskilling of labour.
Functional erythropoietin receptor is undetectable in endothelial, cardiac, neuronal, and renal cells
Authors: Sinclair Angus M. , Coxon Angela , McCaffery Ian , Kaufman Stephen , Paweletz Katherine , Liu Liqin , Busse Leigh , Swift Susan , Elliott Steven , Begley C. Glenn 
Published: February 2010

AbstractErythropoiesis stimulating agents (ESAs) have been reported to activate erythropoietin receptors (EpoR) on cell types, including endothelial, neuronal, renal tubule, and cardiac cells. ESAs have also been reported to promote angiogenesis. However, those findings are controversial and confounded by methodologic issues. We show that EpoR mRNA was detected in essentially all cell types examined, including primary human endothelial, renal, cardiac, and neuronal cells but 10- to 100-fold lower than Epo-responsive cells using quantitative reverse-transcribed polymerase chain reaction. Total endothelial EpoR protein examined using a new monoclonal antibody was low to undetectable. Surface EpoR on endothelial cells was not detected using [125I]-rHuEpo surface-binding studies. There was no evidence of ESA-induced intracellular signaling in endothelial cells. There was a similar lack of EpoR expression and signaling in other cell types examined. Experiments were performed examining ESA function on these cells. An in vivo rat corneal angiogenesis assay demonstrated neo-vessel formation in response to recombinant human vascular endothelial growth factor (rHuVEGF). However, recombinant mouse Epo did not induce vessel formation. Similarly, ESAs did not reproducibly provide cytoprotection to neuronal, renal, or cardiac cells. Taken together, our data challenge the notion of presence or function of EpoR on nonhematopoietic cells, and call into question the preclinical basis for clinical studies exploring direct, “pleiotropic” actions of ESAs.
Monkey hybrid stem cells develop cellular features of Huntington's disease
Authors: Laowtammathron Chuti , Cheng Eric CH , Cheng Pei-Hsun , Snyder Brooke R , Yang Shang-Hsun , Johnson Zach , Lorthongpanich Chanchao , Kuo Hung-Chih , Parnpai Rangsun , Chan Anthony WS 
Published: February 2010

Abstract

Background
Pluripotent stem cells that are capable of differentiating into different cell types and develop robust hallmark cellular features are useful tools for clarifying the impact of developmental events on neurodegenerative diseases such as Huntington's disease. Additionally, a Huntington's cell model that develops robust pathological features of Huntington's disease would be valuable for drug discovery research.

Results
To test this hypothesis, a pluripotent Huntington's disease monkey hybrid cell line (TrES1) was established from a tetraploid Huntington's disease monkey blastocyst generated by the fusion of transgenic Huntington's monkey skin fibroblast and a wild-type non-transgenic monkey oocyte. The TrES1 developed key Huntington's disease cellular pathological features that paralleled neural development. It expressed mutant huntingtin and stem cell markers, was capable of differentiating to neural cells, and developed teratoma in severely compromised immune deficient (SCID) mice. Interestingly, the expression of mutant htt, the accumulation of oligomeric mutant htt and the formation of intranuclear inclusions paralleled neural development in vitro , and even mutant htt was ubiquitously expressed. This suggests the development of Huntington's disease cellular features is influenced by neural developmental events.

Conclusions
Huntington's disease cellular features is influenced by neural developmental events. These results are the first to demonstrate that a pluripotent stem cell line is able to mimic Huntington's disease progression that parallels neural development, which could be a useful cell model for investigating the developmental impact on Huntington's disease pathogenesis.
Mitochondria-targeted antioxidant effects of S(-) and R(+) pramipexole
Authors: Ferrari-Toninelli Giulia , Maccarinelli Giuseppina , Uberti Daniela , Buerger Erich , Memo Maurizio 
Published: February 2010

Abstract

Background
Pramipexole exists as two isomers. The S(-) enantiomer is a potent D3/D2 receptor agonist and is extensively used in the management of PD. In contrast, the R(+) enantiomer is virtually devoid of any of the DA agonist effects. Very limited studies are available to characterize the pharmacological spectrum of the R(+) enantiomer of pramipexole.

Results
Using differentiated SH-SY5Y neuroblastoma cells as an experimental model, here we show that S(-) and R(+) pramipexole are endowed with equipotent efficacy in preventing cell death induced by H2O2 and inhibiting mitochondrial reactive oxygen species generation. Both pramipexole enantiomers prevented mitochondrial ROS generation with a potency about ten times higher then that elicited for neuroprotection.

Conclusions
These results support the concept of both S(-) and R(+) pramipexole enantiomers as mitochondria-targeted antioxidants and suggest that the antioxidant, neuroprotective activity of these drugs is independent of both the chiral 6-propylamino group in the pramipexole molecule and the DA receptor stimulation.
Small RNA interference-mediated gene silencing of heparanase abolishes the invasion, metastasis and angiogenesis of gastric cancer cells
Authors: Zheng Liduan , Jiang Guosong , Mei Hong , Pu Jiarui , Dong Jihua , Hou Xiaohua , Tong Qiangsong 
Published: February 2010

Abstract

Background
Heparanase facilitates the invasion and metastasis of cancer cells, and is over-expressed in many kinds of malignancies. Our studies indicated that heparanase was frequently expressed in advanced gastric cancers. The aim of this study is to determine whether silencing of heparanase expression can abolish the malignant characteristics of gastric cancer cells.

Methods
Three heparanase-specific small interfering RNA (siRNAs) were designed, synthesized, and transfected into cultured gastric cancer cell line SGC-7901. Heparanase expression was measured by RT-PCR, real-time quantitative PCR and Western blot. Cell proliferation was detected by MTT colorimetry and colony formation assay. The in vitro invasion and metastasis of cancer cells were measured by cell adhesion assay, scratch assay and matrigel invasion assay. The angiogenesis capabilities of cancer cells were measured by tube formation of endothelial cells.

Results
Transfection of siRNA against 1496-1514 bp of encoding regions resulted in reduced expression of heparanase, which started at 24 hrs and lasted for 120 hrs post-transfection. The siRNA-mediated silencing of heparanase suppressed the cellular proliferation of SGC-7901 cells. In addition, the in vitro invasion and metastasis of cancer cells were attenuated after knock-down of heparanase. Moreover, transfection of heparanase-specific siRNA attenuated the in vitro angiogenesis of cancer cells in a dose-dependent manner.

Conclusions
These results demonstrated that gene silencing of heparanase can efficiently abolish the proliferation, invasion, metastasis and angiogenesis of human gastric cancer cells in vitro, suggesting that heparanase-specific siRNA is of potential values as a novel therapeutic agent for human gastric cancer.
Heterologous expression of leader-less pga gene in Pichia pastoris: intracellular production of prokaryotic enzyme
Authors: Marešová Helena , Marková Zdena , Valešová Renáta , Sklenář Jan , Kyslík Pavel 
Published: February 2010

Abstract

Background
Penicillin G acylase of Escherichia coli (PGAEc) is a commercially valuable enzyme for which efficient bacterial expression systems have been developed. The enzyme is used as a catalyst for the hydrolytic production of β-lactam nuclei or for the synthesis of semi-synthetic penicillins such as ampicillin, amoxicillin and cephalexin. To become a mature, periplasmic enzyme, the inactive prepropeptide of PGA has to undergo complex processing that begins in the cytoplasm (autocatalytic cleavage), continues at crossing the cytoplasmic membrane (signal sequence removing), and it is completed in the periplasm. Since there are reports on impressive cytosolic expression of bacterial proteins in Pichia, we have cloned the leader-less gene encoding PGAEc in this host and studied yeast production capacity and enzyme authenticity.

Results
Leader-less pga gene encoding PGAEcunder the control of AOX1 promoter was cloned in Pichia pastoris X-33. The intracellular overproduction of heterologous PGAEc(hPGAEc) was evaluated in a stirred 10 litre bioreactor in high-cell density, fed batch cultures using different profiles of transient phases. Under optimal conditions, the average volumetric activity of 25900 U l-1 was reached. The hPGAEc was purified, characterized and compared with the wild-type PGAEc. The α-subunit of the hPGAEc formed in the cytosol was processed aberrantly resulting in two forms with C- terminuses extended to the spacer peptide. The enzyme exhibited modified traits: the activity of the purified enzyme was reduced to 49%, the ratios of hydrolytic activities with cephalexin, phenylacetamide or 6-nitro-3-phenylacetylamidobenzoic acid (NIPAB) to penicillin G increased and the enzyme showed a better synthesis/hydrolysis ratio for the synthesis of cephalexin.

Conclusions
Presented results provide useful data regarding fermentation strategy, intracellular biosynthetic potential, and consequences of the heterologous expression of PGAEc in P. pastoris X-33. Aberrant processing of the precursor of PGAEc in the cytosol yielded the mature enzyme with modified traits.
Determinants of compliance with malaria chemoprophylaxis among French soldiers during missions in inter-tropical Africa
Authors: Resseguier Noémie , Machault Vanessa , Ollivier Lénaick , Orlandi-Pradines Eve , Texier Gaetan , Pradines Bruno , Gaudart Jean , Buguet Alain , Tourette-Turgis Catherine , Rogier Christophe 
Published: February 2010

Abstract

Background
The effectiveness of malaria chemoprophylaxis is limited by the lack of compliance whose determinants are not well known.

Methods
The compliance with malaria chemoprophylaxis has been estimated and analysed by validated questionnaires administered before and after the short-term missions (about four months) in five tropical African countries of 2,093 French soldiers from 19 military companies involved in a prospective cohort study. "Correct compliance" was defined as "no missed doses" of daily drug intake during the entire mission and was analysed using multiple mixed-effect logistic regression model.

Results
The averaged prevalence rate of correct compliance was 46.2%, ranging from 9.6%to 76.6% according to the companies. Incorrect compliance was significantly associated with eveningness (p = 0.028), a medical history of clinical malaria (p < 0.001) and a perceived mosquito attractiveness inferior or superior to the others (p < 0.007). Correct compliance was significantly associated with the systematic use of protective measures against mosquito bites (p < 0.001), the type of military operations (combat vs. training activities, p < 0.001) and other individual factors (p < 0.05).

Conclusions
The identification of circumstances and profiles of persons at higher risk of lack of compliance would pave the way to specifically targeted strategies aimed to improve compliance with malaria chemoprophylaxis and, therefore, its effectiveness.