bluuebunny/crossref_metadata_2025 huggingface dataset:
The Mystery of Modern Wealth: Mercantilism, Value, and the Social Foundations of Liberal International Order
Authors: Boyle Chris
Published: August 2008

Taking its cue from Jacob Viner's classic essay `Power versus Plenty', this article explores the social foundations of one of International Relations' basic analytic categories: `wealth'. An examination of changing notions of economic value in the early-modern period suggests that Viner's assessment of the unenlightened attitudes of mercantilist statesmen needs revision. The rise of a liberal world order presupposes not just a clearer understanding of the nature of value, and how best to obtain it, but a fundamental transformation in the character of value itself — from an attribute of metallic money alone, to an abstract economic property of all human labour. In accounting for this shift we reveal an underlying structure of social relations whose development lies at the root of both our modern notion of value and of the liberal international economy itself.
Geostrategies of the European Neighbourhood Policy
Authors: Browning Christopher S. , Joenniemi Pertti
Published: August 2008

The debate about the European Neighbourhood Policy (ENP) has, in essence, been about borders and bordering. Such departures could contribute — and often do so — to a rather fixed geopolitical vision of what the EU is about and how it aims to run and to organize the broader European space. However, this article aims to retain space for viewing the ENP as a developmental and somewhat fluid process. A conceptual framework, based on outlining three geopolitical models and a series of different geopolitical strategies employed by the EU in regard to its borders, is hence employed in order to be able to tell a more dynamic story regarding the developing nature of the ENP and the EU's evolving nature more generally. The complexity traced informs us that various geostrategies may be held at the same time at the external border. Moreover, the dominance of one geostrategy may be replaced by another or a different combination of them with regard to the same neighbourhood. It is, more generally, argued that if anything it is precisely this dynamism that should be championed as a valuable resource, avoiding the tendency to close off options through the reification of particular visions of the nature of the EU and its borders.
Authenticity as first person practice
Authors: Coghlan David
Published: August 2008

In this article I explore how the notion of authenticity may be grounded in first person practice, rather than in the quality of research data. Drawing on the work of the philosopher-theologian Bernard Lonergan who follows a first person approach and who articulates a notion of authenticity, I explore how authenticity may be framed in terms of being attentive, intelligent, reasonable, and responsible in engaging with the challenges of action research.
Gender Stereotypes and Attitudes Toward Gender Balance in Government
Authors: Dolan Kathleen , Sanbonmatsu Kira
Published: August 2008

The desire to elect more women to public office is likely to affect a range of political behaviors and may explain the relatively low levels of women's descriptive representation overall. Yet, little is known about the public's view of the ideal gender composition of government. We find that the public expresses a preference for higher levels of women's representation than the country has experienced. Women are more likely than men to express a view, though men and women do not differ in their preferences on the ideal percentage of male officeholders. We examine the role of gender stereotypes and the experience of being represented by women officeholders in shaping support for women's representation.
The Death of Cultural Imperialism — and Power Too?
Authors: Demont-Heinrich Christof
Published: August 2008

/ A condensed chapter from a recently completed dissertation, this article critically examines selected texts taken from a pool of 275 accounts of the global rise of English published from 1991 to 2003 in five American-owned prestige press publications — the Los Angeles Times, the International Herald Tribune, The New York Times, The Wall Street Journal and The Washington Post. In particular, it interrogates representations that declare the death of cultural imperialism. The article deconstructs and problematizes these representations along a number of theoretical and analytical lines. The author notes, and challenges, a powerful propensity toward conceiving globalization through the lens of cultural consumption, contending that to focus on cultural consumption and creative appropriation, and to loosely use the catchphrase `cultural flow', is to lose sight of the specific, and considerable, cultural production and distribution inequities that characterize the contemporary global social order. The author also challenges a valorization of individual agency in the texts, as well as a bottom-up view of globalization that implies the disintegration of global power differentials.
The CNN of the Arab World or a Shill for Terrorists?
Authors: Johnson Thomas J. , Fahmy Shahira
Published: August 2008

/ This study surveyed Al-Jazeera viewers through a survey posted on the network's Arabic-language website to examine how credible Al-Jazeera viewers judge the network. Not surprisingly, Al-Jazeera viewers rated the network as highly credible on all measures. They rated CNN and BBC high on expertise, but ranked them low on trustworthiness. Consequently, BBC and CNN were also rated low on other credibility measures. Local Arab media were judged lowest on all credibility measures. Those who were younger and who relied heavily on Al-Jazeera were more likely to judge the network as credible.
Post-Soviet Perspective On Censorship and Freedom of the Media
Authors: Richter Andrei
Published: August 2008

/ This article provides an overview of how journalists and the media in the post-Soviet countries are regulated by law, and of how in the sociopolitical structure of a law-based state their work can be optimized to become a foundation for public accord and stability. The author sees the legal conditions for a free press in the development of mechanisms of journalists' access to information, in the creation of public broadcasting, in the access of political opposition to the public (or state) media, in the denationalization of mass media outlets, etc. Limitations under the pretext of informational sovereignty or the fight against terrorism and political extremism should not undermine ideological and political plurality in the media and society. The article concludes with a comparison of the level of press freedom between all 15 post-Soviet states.
Review: Recurrent stroke: where do we stand with the secondary prevention of noncardioembolic ischaemic strokes?
Authors: Talelli Penelope , Greenwood Richard J.
Published: August 2008

Strokes recur in 6—20% of the patients, most commonly within the first year; after a TIA or minor stroke; most recurrences will occur within the first 90 days. Our ability to identify patients at high risk is poor and most recurrent strokes cannot be explained by traditional risk factors. In 30—45% of the cases the second stroke will be of a different subtype. Moreover, patients are faced with other risks, like cardiac events and cognitive decline. With the population aging, the need for timely and effective secondary prevention strategies is more pressing than ever. This paper summarizes recent advances in pharmacological secondary prevention after a non-cardioembolic ischaemic stroke, and highlights critical questions still in need of answers.
Thiazolidinedione associated volume overload and pulmonary hypertension
Authors: Michaelson Jeffrey
Published: August 2008

Thiazolidinediones are currently indicated for the treatment of Type 2 Diabetes. This class of drugs has been associated with several adverse reactions associated with volume overload. This report describes a case of a 65 year old African—American female with a history of hypertension and obesity, and taking rosiglitazone (Avandia) for her Type 2 Diabetes whose evaluation for chest pain resulted in the incidental finding of pulmonary hypertension noted on echocardiogram. The subsequent evaluation, follow-up and treatment are discussed along with potential pitfalls and implications for clinical care.
The left atrium, atrial fibrillation, and the risk of stroke in hypertensive patients with left ventricular hypertrophy
Authors: Wachtell Kristian , Devereux Richard B. , Lyle Paulette A. , Okin Peter M. , Gerdts Eva
Published: August 2008

The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study provided extensive data on predisposing factors, consequences, and prevention of atrial fibrillation (AF) in patients with hypertension and left ventricular (LV) hypertrophy. Randomized losartan-based treatment was superior to atenolol-based treatment for reducing new-onset AF and complications, especially stroke, associated with new-onset or pre-existing AF. Potential mechanisms of AF prevention by angiotensin receptor blockade supported by LIFE results include greater reduction in left atrial size and LV hypertrophy. Differential effects of antihypertensive treatment on the left atrium and left ventricle may help prevent AF and reduce risk of stroke associated with hypertensive heart disease.
Catalogue of epidermal genes: Genes expressed in the epidermis during larval molt of the silkworm Bombyx mori
Authors: Okamoto Shun , Futahashi Ryo , Kojima Tetsuya , Mita Kazuei , Fujiwara Haruhiko
Published: August 2008

Background

The insect cuticle is composed of various proteins and formed during the molt under hormonal regulation, although its precise composition and formation mechanism are largely unknown. The exhaustive catalogue of genes expressed in epidermis at the molt constitutes a massive amount of information from which to draw a complete picture of the molt and cuticle formation in insects. Therefore, we have catalogued a library of full-length cDNAs (designated epM) from epidermal cells during the last larval molt of Bombyx mori.

Results

Of the 10,368 sequences in the library, we isolated 6,653 usable expressed sequence tags (ESTs), which were categorized into 1,451 nonredundant gene clusters. Seventy-one clusters were considered to be isoforms or premature forms of other clusters. Therefore, we have identified 1,380 putative genes. Of the 6,653 expressed sequences, 48% were derived from 92 cuticular protein genes (RR-1, 24; RR-2, 17; glycine-rich, 29; other classes, 22). A comparison of epM with another epidermal EST data set, epV3 (feeding stage: fifth instar, day 3), showed marked differences in cuticular protein gene. Various types of cuticular proteins are expressed in epM but virtually only RR-1 proteins were expressed in epV3. Cuticular protein genes expressed specifically in epidermis, with several types of expression patterns during the molt, suggest different types of responses to the ecdysteroid pulse. Compared with other Bombyx EST libraries, 13 genes were preferentially included in epM data set. We isolated 290 genes for proteins other than cuticular proteins, whose amino acid sequences retain putative signal peptides, suggesting that they play some role in cuticle formation or in other molting events. Several gene groups were also included in this data set: hormone metabolism, P450, modifier of cuticular protein structure, small-ligand-binding protein, transcription factor, and pigmentation genes.

Conclusion

We have identified 1,380 genes in epM data set and 13 preferentially expressed genes in epidermis at the molt. The comparison of the epM and other EST libraries clarified the totally different gene expression patterns in epidermis between the molting and feeding stages and many novel tissue- and stage-specifically expressed epidermal genes. These data should further our understanding of cuticle formation and the insect molt.
HIV/AIDS awareness and risk behaviour among pregnant women in Semey, Kazakhstan, 2007
Authors: Sandgren Emma , Sandgren Sofia , Urazalin Marat , Andersson Rune
Published: August 2008

Background

Central Asia has one of the most rapidly increasing HIV prevalence in the world. The aim of this study was to evaluate current knowledge, risk behaviour and attitudes to voluntary counselling and testing concerning HIV/AIDS among pregnant women in Semey, Kazakhstan.

Methods

We collected 226 questionnaires in a consecutive sample from a population on 520 pregnant women. The results were related to ethnicity, age and education level.

Results

Ninety-six percent had heard about HIV.

Positive findings were that 89% and 86% of the women were aware of the two main routes of transmission: sexual intercourses without a condom and sharing needles while injecting drugs. The women had first heard about HIV/AIDS through the media with, 52%, and at school with 40%. Only 46% and 68% of the women pointed out breastfeeding and mother-to-child transmission during pregnancy or delivery as routes of transmission. Eighty-three percent were prepared not to breastfeed their baby if they were found to be HIV positive. Slightly more, 86%, accepted the need to take medicine, but fewer women, 68%, were positive to Caesarean section. Negative findings were that only 28% answered that there are ways to protect oneself against sexually transmitted HIV/AIDS and specified that this was condom use.

Conclusion

The pregnant women in Semey have poor knowledge about specific mother-to-child HIV transmission and do not know about the means of reducing mother-to-child HIV infection. The information in the public health program needs to be improved. However, most of the women in Semey were positive to prevention strategies for mother-to-child transmission after hearing about it.
Impact of BRAF, MLH1 on the incidence of microsatellite instability high colorectal cancer in populations based study
Authors: Brim Hassan , Mokarram Pooneh , Naghibalhossaini Fakhraddin , Saberi-Firoozi Mehdi , Al-Mandhari Mansour , Al-Mawaly Kamla , Al-Mjeni Rayhaneh , Al-Sayegh Abeer , Raeburn Sandy , Lee Edward , Giardiello Francis , Smoot Duane T , Vilkin Alexander , Boland C Richard , Goel Ajay , Hafezi Mitra , Nouraie Mehdi , Ashktorab Hassan
Published: August 2008

We have identified an alternative pathway of tumorigenesis in sporadic colon cancer, involving microsatellite instability due to mismatched repair methylation, which may be driven by mutations in the BRAF gene (V600E). Colorectal cancer (CRC) is the most common cancer in the world, and African Americans show a higher incidence than other populations in the United States. We analyzed sporadic CRCs in Omani (of African origin, N = 61), Iranian (of Caucasian origin, N = 53) and African American (N = 95) patients for microsatellite instability, expression status of mismatched repair genes (hMLH1, hMSH2) and presence of the BRAF (V600E) mutation. In the Omani group, all tumors with BRAF mutations were located in the left side of the colon, and for African Americans, 88% [7] of tumors with BRAF mutations were found in the right side of the colon. In African Americans, 31% of tumors displayed microsatellite instability at two or more markers (MSI-H), while this rate was 26% and 13% for tumors in the Iranian and Omani groups, respectively. A majority of these MSI-H tumors were located in the proximal colon (right side) in African American and Iranian subjects, whereas most were located in the distal colon (left side) in Omani subjects. Defects in hMLH1 gene expression were found in 77% of MSI-H tumors in both African Americans and Iranians and in 38% of tumors in Omanis. BRAF mutations were observed in all subjects: 10% of tumors in African Americans (8/82), 2% of tumors in Iranians (1/53), and 19% of tumors in Omanis (11/59). Our findings suggest that CRC occurs at a younger age in Omani and Iranian patients, and these groups showed a lower occurrence of MSI-H than did African American patients. Our multivariate model suggests an important and significant role of hMLH1 expression and BRAF mutation in MSI-H CRC in these populations. The high occurrence of MSI-H tumors in African Americans may have significant implications for treatment, since patients with MSI-H lesions display a different response to chemotherapeutic agents such as 5-fluorouracil.
The costs of traumatic brain injury due to motorcycle accidents in Hanoi, Vietnam
Authors: Hoang Hanh TM , Pham Tran L , Vo Thuy TN , Nguyen Phuong K , Doran Christopher M , Hill Peter S
Published: August 2008

Background

Road traffic accidents are the leading cause of fatal and non-fatal injuries in Vietnam. The purpose of this study is to estimate the costs, in the first year post-injury, of non-fatal traumatic brain injury (TBI) in motorcycle users not wearing helmets in Hanoi, Vietnam. The costs are calculated from the perspective of the injured patients and their families, and include quantification of direct, indirect and intangible costs, using years lost due to disability as a proxy.

Methods

The study was a retrospective cross-sectional study. Data on treatment and rehabilitation costs, employment and support were obtained from patients and their families using a structured questionnaire and The European Quality of Life instrument (EQ6D).

Results

Thirty-five patients and their families were interviewed. On average, patients with severe, moderate and minor TBI incurred direct costs at USD 2,365, USD 1,390 and USD 849, with time lost for normal activities averaging 54 weeks, 26 weeks and 17 weeks and years lived with disability (YLD) of 0.46, 0.25 and 0.15 year, respectively.

Conclusion

All three component costs of TBI were high; the direct cost accounted for the largest proportion, with costs rising with the severity of TBI. The results suggest that the burden of TBI can be catastrophic for families because of high direct costs, significant time off work for patients and caregivers, and impact on health-related quality of life. Further research is warranted to explore the actual social and economic benefits of mandatory helmet use.
Identification of intra-group, inter-individual, and gene-specific variances in mRNA expression profiles in the rheumatoid arthritis synovial membrane
Authors: Huber René , Hummert Christian , Gausmann Ulrike , Pohlers Dirk , Koczan Dirk , Guthke Reinhard , Kinne Raimund W
Published: August 2008

Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory and destructive joint disease characterized by overexpression of pro-inflammatory/pro-destructive genes and other activating genes (for example, proto-oncogenes) in the synovial membrane (SM). The gene expression in disease is often characterized by significant inter-individual variances via specific synchronization/desynchronization of gene expression. To elucidate the contribution of the variance to the pathogenesis of disease, expression variances were tested in SM samples of RA patients, osteoarthritis (OA) patients, and normal controls (NCs).

Method

Analysis of gene expression in RA, OA, and NC samples was carried out using Affymetrix U133A/B oligonucleotide arrays, and the results were validated by real-time reverse transcription-polymerase chain reaction. For the comparison between RA and NC, 568 genes with significantly different variances in the two groups (P≤ 0.05; Bonferroni/Holm corrected Brown-Forsythe version of the Levene test) were selected. For the comparison between RA and OA, 333 genes were selected. By means of theKyoto Encyclopedia of Genes and Genomes, the pathways/complexes significantly affected by higher gene expression variances were identified in each group.

Results

Ten pathways/complexes significantly affected by higher gene expression variances were identified in RA compared with NC, including cytokine–cytokine receptor interactions, the transforming growth factor-beta pathway, and anti-apoptosis. Compared with OA, three pathways with significantly higher variances were identified in RA (for example, B-cell receptor signaling and vascular endothelial growth factor signaling). Functionally, the majority of the identified pathways are involved in the regulation of inflammation, proliferation, cell survival, and angiogenesis.

Conclusion

In RA, a number of disease-relevant or even disease-specific pathways/complexes are characterized by broad intra-group inter-individual expression variances. Thus, RA pathogenesis in different individuals may depend to a lesser extent on common alterations of the expression of specific key genes, and rather on individual-specific alterations of different genes resulting in common disturbances of key pathways.
Inflammatory and transcriptional roles of poly (ADP-ribose) polymerase in ventilator-induced lung injury
Authors: Kim Je Hyeong , Suk Min Hyun , Yoon Dae Wui , Kim Hye Young , Jung Ki Hwan , Kang Eun Hae , Lee Sung Yong , Lee Sang Yeub , Suh In Bum , Shin Chol , Shim Jae Jeong , In Kwang Ho , Yoo Se Hwa , Kang Kyung Ho
Published: August 2008

Introduction

Poly (ADP-ribose) polymerase (PARP) participates in inflammation by cellular necrosis and the nuclear factor-kappa-B (NF-κB)-dependent transcription. The purpose of this study was to examine the roles of PARP in ventilator-induced lung injury (VILI) in normal mice lung.

Methods

Male C57BL/6 mice were divided into four groups: sham tracheostomized (sham), lung-protective ventilation (LPV), VILI, and VILI with PARP inhibitor PJ34 pretreatment (PJ34+VILI) groups. Mechanical ventilation (MV) settings were peak inspiratory pressure (PIP) 15 cm H2O + positive end-expiratory pressure (PEEP) 3 cm H2O + 90 breaths per minute for the LPV group and PIP 40 cm H2O + PEEP 0 cm H2O + 90 breaths per minute for the VILI and PJ34+VILI groups. After 2 hours of MV, acute lung injury (ALI) score, wet-to-dry (W/D) weight ratio, PARP activity, and dynamic compliance (CD) were recorded. Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), myeloperoxidase (MPO) activity, and nitrite/nitrate (NOX) in the bronchoalveolar lavage fluid and NF-κB DNA-binding activity in tissue homogenates were measured.

Results

The VILI group showed higher ALI score, W/D weight ratio, MPO activity, NOX, and concentrations of TNF-α and IL-6 along with lower CD than the sham and LPV groups (P < 0.05). In the PJ34+VILI group, PJ34 pretreatment improved all histopathologic ALI, inflammatory profiles, and pulmonary dynamics (P < 0.05). NF-κB activity was increased in the VILI group as compared with the sham and LPV groups (P < 0.05) and was decreased in the PJ34+VILI group as compared with the VILI group (P = 0.009). Changes in all parameters were closely correlated with the PARP activity (P < 0.05).

Conclusion

Overactivation of PARP plays an important role in the inflammatory and transcriptional pathogenesis of VILI, and PARP inhibition has potentially beneficial effects on the prevention and treatment of VILI.
Prognostic value of brain natriuretic peptide in acute pulmonary embolism
Authors: Coutance Guillaume , Le Page Olivier , Lo Ted , Hamon Martial
Published: August 2008

Introduction

The relationship between brain natriuretic peptide (BNP) increase in acute pulmonary embolism (PE) and the increase in mortality and morbidity has frequently been suggested in small studies but its global prognostic performance remains largely undefined. We performed a systematic review and meta-analysis of data to examine the prognostic value of elevated BNP for short-term all-cause mortality and serious adverse events.

Methods

The authors reviewed PubMed, BioMed Central, and the Cochrane database and conducted a manual review of article bibliographies. Using a prespecified search strategy, we included a study if it used BNP or N-terminal pro-BNP biomarkers as a diagnostic test in patients with documented PE and if it reported death, the primary endpoint of the meta-analysis, in relation to BNP testing. Studies were excluded if they were performed in patients without certitude of PE or in a subset of patients with cardiogenic shock. Twelve relevant studies involving a total of 868 patients with acute PE at baseline were included in the meta-analysis using a random-effects model.

Results

Elevated BNP levels were significantly associated with short-term all-cause mortality (odds ratio [OR] 6.57, 95% confidence interval [CI] 3.11 to 13.91), with death resulting from PE (OR 6.10, 95% CI 2.58 to 14.25), and with serious adverse events (OR 7.47, 95% CI 4.20 to 13.15). The corresponding positive and negative predictive values for death were 14% (95% CI 11% to 18%) and 99% (95% CI 97% to 100%), respectively.

Conclusion

This meta-analysis indicates that, while elevated BNP levels can help to identify patients with acute PE at high risk of death and adverse outcome events, the high negative predictive value of normal BNP levels is certainly more useful for clinicians to select patients with a likely uneventful follow-up.
Dynamics of lung macrophage activation in response to helminth infection
Authors: Siracusa Mark C , Reece Joshua J , Urban Joseph F , Scott Alan L
Published: August 2008

Most of our understanding of the development and phenotype of alternatively activated macrophages (AAMs) has been obtained from studies investigating the response of bone marrow- and peritoneal-derived cells to IL-4 or IL-13 stimulation. Comparatively little is known about the development of AAMs in the lungs, and how the complex signals associated with pulmonary inflammation influence the AAM phenotype. Here, we use Nippostrongylus brasiliensis to initiate AAM development and define the dynamics of surface molecules, gene expression, and cell function of macrophages isolated from lung tissue at different times postinfection (PI). Initially, lung macrophages take on a foamy phenotype, up-regulate MHC and costimulatory molecules, express reduced levels of TNF and IL-12, and undergo proliferation. Cells isolated between days 8 and 15 PI adopt a dense, granular phenotype and exhibit reduced levels of costimulatory molecules and elevated levels of programmed death ligand-1 (PDL-1) and PDL-2 and an increase in IL-10 expression. Functionally, AAMs isolated on days 13–15 PI demonstrate an enhanced capacity to take up and sequester antigen. However, these same cells did not mediate antigen-specific T cell proliferation and dampened the proliferation of CD3/CD28-activated CD4+ T cells. These data indicate that the alternative activation of macrophages in the lungs, although initiated by IL-4/IL-13, is a dynamic process that is likely to be influenced by other immune and nonimmune factors in the pulmonary environment.
A novel subset of NK cells expressing high levels of inhibitory FcγRIIB modulating antibody-dependent function
Authors: Dutertre Charles-Antoine , Bonnin-Gélizé Emmanuelle , Pulford Karen , Bourel Dominique , Fridman Wolf-Herman , Teillaud Jean-Luc
Published: August 2008

NK cells can kill antibody-coated target cells following engagement of FcγRIIIA, the major activating FcγR expressed by these cells. The presence of FcγRIIC (CD32C) has also been reported, but its contribution to the FcγR-dependent effector functions of NK cells remains debated. We demonstrate here that inhibitory FcγRIIB is also expressed by a small subset of CD56+/NKp46+ NK cells and can efficiently down-modulate their FcγR-dependent effector function. Immunofluorescence analyses of NK cells from 52 healthy donors showed the presence of CD56bright/FcγRII− (5.2%±3.4), CD56dim/FcγRIIlo/- (94.1%±3.4), and CD56dim/FcγRIIbright (0.64%±0.72) cells. QRT-PCR and protein analyses performed on isolated FcγRIIbright NK cells indicated that FcγRIIB is strongly expressed by these cells but not by FcγRIIlo/- cells. In addition, FcγRIIbright cells showed a weaker antibody-dependent degranulation when incubated with IgG-coated target cells compared with FcγRIIlo/- NK cells, although a strong FcγRIIIA expression was detected in both cells. Furthermore, the addition of anti-FcγRII Fab paralleled a higher degranulation of FcγRIIbright NK cells, indicating a direct role for FcγRIIB in this down-modulating effect. Thus, it is proposed that FcγRIIBbright NK cells represent a new NK cell compartment able to down-modulate NK cell functions triggered by the engagement of activating FcγR.
EGCG Stabilizes p27kip1 in E2-Stimulated MCF-7 Cells through Down-Regulation of the Skp2 Protein
Authors: Huang Hsiu-Chen , Way Tzong-Der , Lin Chih-Li , Lin Jen-Kun
Published: August 2008

Loss of p27Kip1 is associated with a poor prognosis in breast cancer. According to previous findings, a decrease in p27Kip1 levels is mainly the result of enhanced proteasome-dependent degradation mediated by its specific ubiquitin ligase subunit S-phase kinase protein 2 (Skp2). Epigallocatechin-3-gallate (EGCG), the main constituent of green tea, was found to stabilize p27Kip1 levels in breast cancer, but whether this effect is mediated through changes in Skp2 expression remains unclear. Here we investigated the mechanisms involved in EGCG’s growth inhibition of estrogen-responsive human breast cancer MCF-7 cells. In our results, EGCG increased p27Kip1 and decreased Skp2 in a time- and dose-dependent manner, suggesting that p27Kip1 and Skp2 may be involved in the growth inhibition by EGCG in estrogen-stimulated MCF-7 cells. Interestingly, mRNA levels of p27Kip1 and Skp2 did not significantly change in estrogen-stimulated MCF-7 cells after EGCG treatments. Moreover, overexpression of Skp2 in MCF-7 cells prevented accumulation of p27Kip1 and promoted resistance to the antiproliferative effects of EGCG. This suggests that the down-regulation of the F-box protein Skp2 is the mechanism underlying p27Kip1 accumulation. Furthermore, both tamoxifen and paclitaxel significantly and synergistically enhanced the growth inhibition of MCF-7 cells by EGCG through the down-regulation of Skp2 protein. However, the down-regulation of Skp2 was not always correlate with the up-regulation of p27, suggesting that EGCG-dependent Skp2 down-regulation can influence cell growth in several ways. The therapeutic strategies designed to reduce Skp2 may therefore play an important clinical role in treatment of breast cancer cells.
Urocortin 1 Inhibits Rat Leydig Cell Function
Authors: Rivier Catherine L.
Published: August 2008

Corticotropin-releasing factor (CRF) has previously been reported in rat testes in which it inhibits Leydig cells activity. However, recent studies in our laboratory have suggested that some of the effects originally attributed to CRF were instead due to the related peptide Urocortin 1 (Ucn 1) and that this latter hormone, not CRF, was detectable in Leydig cells. We show here that Ucn 1 [a mixed CRF receptor (CRFR) type 1 and CRFR2 agonist] and the CRFR1-selective peptide Stressin 1, but not Ucn 2 or Ucn 3 (both considered selective CRFR2 ligands), significantly blunt the testosterone response to human chorionic gonadotropin. The effect of Ucn 1 is observed regardless of whether this peptide is injected iv or directly into the testes, and it is reversed by the mixed CRFR1/R2 antagonist Astressin B. Blockade of GnRH receptors with the antagonist Azalin B does not interfere with the influence of Ucn 1, thereby demonstrating that pituitary luteinizing hormone does not appear to be involved in this model. Collectively these results suggest that Ucn 1, not CRF, is present in the rat testes and interferes with Leydig cell activity. However, whereas we previously reported that alcohol up-regulated gonadal Ucn 1 gene expression, CRF receptor antagonists were unable to reverse the inhibitory effect exerted by alcohol on human chorionic gonadotropin-induced testosterone release. The functional role played by testicular Ucn 1 in stress models characterized by blunted androgen levels therefore needs to be further investigated.
Pharmacological Demarcation of the Growth Hormone, Gut Motility and Feeding Effects of Ghrelin Using a Novel Ghrelin Receptor Agonist
Authors: Fraser Graeme L. , Hoveyda Hamid R. , Tannenbaum Gloria Shaffer
Published: August 2008

The peptide hormone ghrelin exerts a wide spectrum of activities including the stimulation of GH release, feeding, and gastrointestinal motility, purportedly via the activation of a common receptor, GH secretagogue receptor (since renamed the GRLN-R) The aim of the present study was to determine whether these effects can be separated pharmacologically. Tranzyme Pharma (TZP)-101 is a small-molecule agonist with potent binding affinity (inhibitory constant = 16 nm) and full agonist activity (EC50 = 29 nm, maximum response = 111%) at the human recombinant GRLN-R. Pharmacokinetic profiling of TZP-101 in rat determined a plasma elimination half-life of 99 min and low blood-brain barrier permeability (0.09%). The pharmacological response to TZP-101, administered centrally [intracerebroventricular (icv)] or peripherally (iv), was evaluated in comparison with that of acylated ghrelin. Thus, TZP-101 (iv) accelerated gastric emptying of a liquid meal (2% methylcellulose) similarly to ghrelin (iv). IAlso, TZP-101 (icv) stimulated spontaneous, cumulative food intake in a similar manner to ghrelin (icv). However, unlike ghrelin, TZP-101 did not elicit significant GH release on either central or peripheral administration. Moreover, TZP-101 did not alter ghrelin-induced GH release. n total, these data demonstrate that the GH response can be pharmacologically demarcated from the orexigenic and gastrointestinal responses to ghrelin in rats. The observation that the centrally mediated orexigenic response and the peripherally mediated gastric motility response are pharmacologically associated is consistent with the classification of ghrelin as a brain-gut peptide, whereas the additional action of ghrelin to stimulate GH release (possibly via a distinct signaling pathway) may be considered a complementary mechanism to harmonize somatic growth and body composition with the regulation of energy homeostasis.
Characterization of Thyrotropin Receptor Antibody-Induced Signaling Cascades
Authors: Morshed Syed A. , Latif Rauf , Davies Terry F.
Published: August 2008

The TSH receptor (TSHR) is constitutively active and is further enhanced by TSH ligand binding or by stimulating TSHR antibodies (TSHR-Abs) as seen in Graves’ disease. TSH is known to activate the thyroid epithelial cell via both Gαs-cAMP/protein kinase A/ERK and Gαq-Akt/protein kinase C coupled signaling networks. The recent development of monoclonal antibodies to the TSHR has enabled us to investigate the hypothesis that different TSHR-Abs may have unique signaling imprints that differ from TSH ligand itself. We have, therefore, performed sequential studies, using rat thyrocytes (FRTL-5, passages 5–20) as targets, to examine the signaling pathways activated by a series of monoclonal TSHR-Abs in comparison with TSH itself. Activation of key signaling molecules was estimated by specific immunoblots and/or enzyme immunoassays. Continuing constitutive TSHR activity in thyroid cells, deprived of TSH and serum for 48 h, was demonstrated by pathway-specific chemical inhibition. Under our experimental conditions, TSH ligand and TSHR-stimulating antibodies activated both Gαs and Gαq effectors. Importantly, some TSHR-blocking and TSHR-neutral antibodies were also able to generate signals, influencing primarily the Gαq effectors and induced cell proliferation. Most strikingly, antibodies that used the Gαq cascades used c-Raf-ERK-p90RSK as a unique signaling cascade not activated by TSH. Our study demonstrated that individual TSHR-Abs had unique molecular signatures which resulted in sequential preferences. Because downstream thyroid cell signaling by the TSHR is both ligand dependent and independent, this may explain why TSHR-Abs are able to have variable influences on thyroid cell biology.

Antibodies to the TSH receptor produce unique signaling imprints which differ from its ligand, indicating that these antibodies have variable effects on thyroid cell biology.
Bioluminescent response of individual dinoflagellate cells to hydrodynamic stress measured with millisecond resolution in a microfluidic device
Authors: Latz Michael I. , Bovard Michelle , VanDelinder Virginia , Segre Enrico , Rohr Jim , Groisman Alex
Published: August 2008

Dinoflagellate bioluminescence serves as a model system for examining mechanosensing by suspended motile unicellular organisms. The response latency, i.e. the delay time between the mechanical stimulus and luminescent response, provides information about the mechanotransduction and signaling process, and must be accurately known for dinoflagellate bioluminescence to be used as a flow visualization tool. This study used a novel microfluidic device to measure the response latency of a large number of individual dinoflagellates with a resolution of a few milliseconds. Suspended cells of several dinoflagellate species approximately 35 μm in diameter were directed through a 200 μm deep channel to a barrier with a 15 μm clearance impassable to the cells. Bioluminescence was stimulated when cells encountered the barrier and experienced an abrupt increase in hydrodynamic drag, and was imaged using high numerical aperture optics and a high-speed low-light video system. The average response latency for Lingulodinium polyedrum strain HJ was 15 ms (N>300 cells) at the three highest flow rates tested, with a minimum latency of 12 ms. Cells produced multiple flashes with an interval as short as 5 ms between individual flashes,suggesting that repeat stimulation involved a subset of the entire intracellular signaling pathway. The mean response latency for the dinoflagellates Pyrodinium bahamense, Alexandrium monilatumand older and newer isolates of L. polyedrum ranged from 15 to 22 ms,similar to the latencies previously determined for larger dinoflagellates with different morphologies, possibly reflecting optimization of dinoflagellate bioluminescence as a rapid anti-predation behavior.
The movements of limb segments and joints during locomotion in African and Asian elephants
Authors: Ren Lei , Butler Melanie , Miller Charlotte , Paxton Heather , Schwerda Delf , Fischer Martin S. , Hutchinson John R.
Published: August 2008

As the largest extant terrestrial animals, elephants do not trot or gallop but can move smoothly to faster speeds without markedly changing their kinematics, yet with a shift from vaulting to bouncing kinetics. To understand this unusual mechanism, we quantified the forelimb and hindlimb motions of eight Asian elephants (Elephas maximus) and seven African elephants(Loxodonta africana). We used 240 Hz motion analysis (tracking 10 joint markers) to measure the flexion/extension angles and angular velocities of the limb segments and joints for 288 strides across an eightfold range of speeds (0.6–4.9 m s–1) and a sevenfold range of body mass (521–3684 kg). We show that the columnar limb orientation that elephants supposedly exemplify is an oversimplification – few segments or joints are extremely vertical during weight support (especially at faster speeds), and joint flexion during the swing phase is considerable. The`inflexible' ankle is shown to have potentially spring-like motion, unlike the highly flexible wrist, which ironically is more static during support. Elephants use approximately 31–77% of their maximal joint ranges of motion during rapid locomotion, with this fraction increasing distally in the limbs, a trend observed in some other running animals. All angular velocities decrease with increasing size, whereas smaller elephant limbs are not markedly more flexed than adults. We find no major quantitative differences between African and Asian elephant locomotion but show that elephant limb motions are more similar to those of smaller animals, including humans and horses, than commonly recognized. Such similarities have been obscured by the reliance on the term `columnar' to differentiate elephant limb posture from that of other animals. Our database will be helpful for identifying elephants with unusual limb movements, facilitating early recognition of musculoskeletal pathology.
Chemical and mechanical bioerosion of boring sponges from Mexican Pacific coral reefs
Authors: Nava Héctor , Carballo José Luis
Published: August 2008

Species richness (S) and frequency of invasion (IF) by boring sponges on living colonies of Pocillopora spp. from National Park Isla Isabel(México, East Pacific Ocean) are presented. Twelve species belonging to the genera Aka, Cliona, Pione, Thoosa and Spheciospongia were found, and 56% of coral colonies were invaded by boring sponges, with Cliona vermifera Hancock 1867 being the most abundant species (30%). Carbonate dissolution rate and sediment production were quantified for C. vermifera and Cliona flavifodinaRützler 1974. Both species exhibited similar rates of calcium carbonate(CaCO3) dissolution (1.2±0.4 and 0.5±0.2 kg CaCO3 m–2 year–1, respectively,mean ± s.e.m.), and sediment production (3.3±0.6 and 4.6±0.5 kg CaCO3 m–2year–1), resulting in mean bioerosion rates of 4.5±0.9 and 5.1±0.5 kg CaCO3 m–2year–1, respectively. These bioerosion rates are close to previous records of coral calcification per unit of area, suggesting that sponge bioerosion alone can promote disequilibrium in the reef accretion/destruction ratio in localities that are heavily invaded by boring sponges. The proportion of dissolved material by C. vermifera and C. flavifodina (27 and 10.2%, respectively) confirms that chemical bioerosion plays an important role in sponge bioerosion and in the CaCO3 cycle in coral reefs.
Comparing memory-forming capabilities between laboratory-reared and wildLymnaea: learning in the wild, a heritable component of snail memory
Authors: Orr Michael V. , Hittel Karla , Lukowiak Ken
Published: August 2008

We set out to determine whether the ability to form long-term memory (LTM)is influenced by laboratory rearing. We investigated the ability of four populations of Lymnaea stagnalis to form LTM following operant conditioning both in the freely behaving animal and at the electrophysiological level in a neuron, RPeD1, which is a necessary site for LTM. We hypothesized that laboratory rearing results in a decreased ability to form LTM because rearing does not occur in an `enriched environment'. Of the four populations examined, two were collected in the wild and two were reared in the laboratory – specifically, (1) wild Dutch snails; (2) their laboratory-reared offspring; (3) wild Southern Alberta snails (Belly); and (4)their laboratory-reared offspring. We found that Belly snails had an enhanced capability of forming LTM compared with Dutch laboratory-reared snails. That is, the Belly snails, which are much darker in colour than laboratory-reared snails (i.e. blonds), were `smarter'. However, when we tested the offspring of Belly snails reared in the laboratory we found that these snails still had the enhanced ability to form LTM, even though they were now just as `blond' as their laboratory-reared Dutch cousins. Finally, we collected wild Dutch snails, which are also dark, and found that their ability to form LTM was not different to that of their laboratory-reared offspring. Thus, our hypothesis was not proved. Rather, we now hypothesize that there are strain differences between the Belly and Dutch snails, irrespective of whether they are reared in the wild or in the laboratory.
C. elegans and H. sapiens mRNAs with edited 3′ UTRs are present on polysomes
Authors: Hundley Heather A. , Krauchuk Ammie A. , Bass Brenda L.
Published: August 2008

Adenosine deaminases that act on RNA (ADARs) are editing enzymes that convert adenosine to inosine in double-stranded RNA (dsRNA). ADARs sometimes target codons so that a single mRNA yields multiple protein isoforms. However, ADARs most often target noncoding regions of mRNAs, such as untranslated regions (UTRs). To understand the function of extensive double-stranded 3′ UTR structures, and the inosines within them, we monitored the fate of reporter and endogenous mRNAs that include structured 3′ UTRs in wild-type Caenorhabditis elegans and in strains with mutations in the ADAR genes. In general, we saw little effect of editing on stability or translatability of mRNA, although in one case an ADR-1 dependent effect was observed. Importantly, whereas previous studies indicate that inosine-containing RNAs are retained in the nucleus, we show that both C. elegans and Homo sapiens mRNAs with edited, structured 3′ UTRs are present on translating ribosomes.
The Value of Information and Intensity of Preference
Authors: Delquié Philippe
Published: August 2008

Previous research has documented the lack of clear relationships between the value of information and characteristics of the decision problem. This paper shows that the intensity of the decision maker's preference toward the prior choice alternatives can be regarded as the primary determinant of information value. The value of an information source, measured in utility units, is maximal when the decision maker is indifferent vis-à-vis the prior alternatives, and it is lower as the preference for one alternative over the others gets stronger. This holds under quite general conditions, which are made explicit, and for any decision maker's utility function, wealth, and background risks. The maximum buying price of information follows the same pattern for linear utility and, with a restriction, exponential utility, and this may hold approximately for other types of utility functions. The result provides a general, concise, and intuitive explanation for seemingly ill-behaved variations in the value of information. It indicates that nonmonotonic, quasi-concave relationships should generally be expected between value of information and parameters of the decision problem.
Reoptimization Approaches for the Vehicle-Routing Problem with Stochastic Demands
Authors: Secomandi Nicola , Margot François
Published: August 2008

We consider the vehicle-routing problem with stochastic demands (VRPSD) under reoptimization. We develop and analyze a finite-horizon Markov decision process (MDP) formulation for the single-vehicle case and establish a partial characterization of the optimal policy. We also propose a heuristic solution methodology for our MDP, named partial reoptimization, based on the idea of restricting attention to a subset of all the possible states and computing an optimal policy on this restricted set of states. We discuss two families of computationally efficient partial reoptimization heuristics and illustrate their performance on a set of instances with up to and including 100 customers. Comparisons with an existing heuristic from the literature and a lower bound computed with complete knowledge of customer demands show that our best partial reoptimization heuristics outperform this heuristic and are on average no more than 10%–13% away from this lower bound, depending on the type of instances.
Retrieval‐induced forgetting in normal ageing
Authors: Hogge Michaël. , Adam Stéphane. , Collette Fabienne.
Published: August 2008

The retrieval‐induced forgetting (RIF) paradigm was used to assess the integrity of unintentional inhibitory functioning in normal ageing. The paradigm was adapted to explore the RIF effect under conditions that allow us to differentiate the contribution of intentional and automatic retrieval processes to performance. The results showed the presence of equivalent and significant RIF effects in young and older adults, for both the intentional and automatic retrieval performance. These results suggest that unintentional inhibitory processes are spared in normal ageing and confirm that RIF effect is independent of the kind of memory processes involved in task performance.