bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Group Consciousness Theories to Understand Political Activism: Case Studies of Barack Obama, Hillary Clinton, and Ingo Hasselbach
Authors: Duncan Lauren E.
Published: October 2010

ABSTRACTI describe and integrate several theories of group consciousness and collective action, along with 3 case studies of political activists. I have 2 goals: (1) to use the theories to help us understand something puzzling about each life and (2) to use the cases to complicate and expand the theories. Barack Obama's case raises the question of how someone with a politicized Black identity evolved into a politician working for all oppressed people and complicates racial identity development theory. Hillary Clinton's case raises the question of how a middle‐class White girl raised in a conservative family became a prominent Democratic Party politician and complicates group consciousness theories by demonstrating the importance of generation and personality. Ingo Hasselbach's (a former German neo‐Nazi leader) case illustrates relative deprivation theory and raises the question of whether theories developed to explain subordinate group consciousness can be applied to movements of dominant group consciousness.
Why Achievement Motivation Predicts Success in Business but Failure in Politics: The Importance of Personal Control
Authors: Winter David G.
Published: October 2010

ABSTRACT
Several decades of research have established that implicit achievement motivation (n Achievement) is associated with success in business, particularly in entrepreneurial or sales roles. However, several political psychology studies have shown that achievement motivation is not associated with success in politics; rather, implicit power motivation often predicts political success. Having versus lacking control may be a key difference between business and politics. Case studies suggest that achievement‐motivated U.S. presidents and other world leaders often become frustrated and thereby fail because of lack of control, whereas power‐motivated presidents develop ways to work with this inherent feature of politics. A reevaluation of previous research suggests that, in fact, relationships between achievement motivation and business success only occur when control is high. The theme of control is also prominent in the development of achievement motivation. Cross‐national data are also consistent with this analysis: In democratic industrialized countries, national levels of achievement motivation are associated with strong executive control. In countries with low opportunity for education (thus fewer opportunities to develop a sense of personal control), achievement motivation is associated with internal violence. Many of these manifestations of frustrated achievement motivation in politics resemble authoritarianism. This conclusion is tested by data from a longitudinal study of 113 male college students, showing that high initial achievement motivation combined with frustrated desires for control is related to increases in authoritarianism (F‐scale scores) during the college years. Implications for the psychology of leadership and practical politics are discussed.
The Cognitive Processing of Politics and Politicians: Archival Studies of Conceptual and Integrative Complexity
Authors: Suedfeld Peter
Published: October 2010

ABSTRACT
This article reviews over 30 years of research on the role of integrative complexity (IC) in politics. IC is a measure of the cognitive structure underlying information processing and decision making in a specific situation and time of interest to the researcher or policymaker. As such, it is a state counterpart of conceptual complexity, the trait (transsituationally and transtemporally stable) component of cognitive structure. In the beginning (the first article using the measure was published in 1976), most of the studies were by the author or his students (or both), notably Philip Tetlock; more recently, IC has attracted the attention of a growing number of political and social psychologists.

The article traces the theoretical development of IC; describes how the variable is scored in archival or contemporary materials (speeches, interviews, memoirs, etc.); discusses possible influences on IC, such as stress, ideology, and official role; and presents findings on how measures of IC can be used to forecast political decisions (e.g., deciding between war and peace). Research on the role of IC in individual success and failure in military and political leaders is also described.
Personality and Support for Universal Human Rights: A Review and Test of a Structural Model
Authors: McFarland Sam
Published: October 2010

ABSTRACT
All individual differences that predict support for international human rights are first reviewed: support for human rights is linked most positively to “globalism” (other international and environmental concerns), “identification with all humanity,” principled moral reasoning, benevolence, and dispositional empathy. It is related most negatively to ethnocentrism and its root dispositions, the social dominance orientation, and authoritarianism. Other correlates are also noted. Secondly, a structural model of the effects of authoritarianism, social dominance, ethnocentrism and identification with all humanity upon commitment to human rights is presented and tested. Across 2 studies (Study 1, N=218 nonstudent adults; Study 2, N=102 university students), ethnocentrism and identification with all humanity directly predicted human rights commitment. The effects of authoritarianism upon this commitment were fully mediated through enhanced ethnocentrism and reduced identification with all humanity. The effects of social dominance were similar, but its direct effect upon human rights commitment remained significant and was not, in the second study, mediated by reduced dispositional empathy.
The Relationship Between Social‐Cultural Attitudes and Behavioral Measures of Cognitive Style: A Meta‐Analytic Integration of Studies
Authors: Van Hiel Alain , Onraet Emma , De Pauw Sarah
Published: October 2010

ABSTRACT
The present meta‐analysis investigates the relationship between social‐cultural right‐wing attitudes and objective measures of cognitive style on a set of 124 unique samples, with a total of 29,209 participants. Intolerance of ambiguity and cognitive ability yielded relationships of moderate strength with right‐wing attitudes, whereas only mixed evidence was obtained for rigidity, complexity, and field dependence. In the discussion, we compare the present weak to moderate relationships with a meta‐analysis conducted by Jost, Glaser, Kruglanski, and Sulloway (2003b), included predominantly self‐report measures of cognitive style, reporting moderate to strong relationships between conservatism. The need to study cognitive ability as a basis of ideological attitudes is also discussed.
Personality, Ideology, Prejudice, and Politics: A Dual‐Process Motivational Model
Authors: Duckitt John , Sibley Chris G.
Published: October 2010

ABSTRACT
Early theorists assumed that sociopolitical or ideological attitudes were organized along a single left‐right dimension and directly expressed a basic personality dimension. Empirical findings, however, did not support this and suggested that there seem to be 2 distinct ideological attitude dimensions, best captured by the constructs of right‐wing authoritarianism and social dominance orientation, which express 2 distinct sets of motivational goals or values. We outline a dual‐process motivational (DPM) model of how these 2 dimensions originate from particular personality dispositions and socialized worldview beliefs and how and why their different underlying motivational goals or values generate their wide‐ranging effects on social outcomes, such as prejudice and politics. We then review new research bearing on the model and conclude by noting promising directions for future research.
Learning by creating and exchanging objects: The SCY experience
Authors: De Jong Ton , Van Joolingen Wouter R. , Giemza Adam , Girault Isabelle , Hoppe Ulrich , Kindermann Jörg , Kluge Anders , Lazonder Ard W. , Vold Vibeke , Weinberger Armin , Weinbrenner Stefan , Wichmann Astrid , Anjewierden Anjo , Bodin Marjolaine , Bollen Lars , D′Ham Cédric , Dolonen Jan , Engler Jan , Geraedts Caspar , Grosskreutz Henrik , Hovardas Tasos , Julien Rachel , Lechner Judith , Ludvigsen Sten , Matteman Yuri , Meistadt Øyvind , Næss Bjørge , Ney Muriel , Pedaste Margus , Perritano Anthony , Rinket Marieke , Von Schlanbusch Henrik , Sarapuu Tago , Schulz Florian , Sikken Jakob , Slotta Jim , Toussaint Jeremy , Verkade Alex , Wajeman Claire , Wasson Barbara , Zacharia Zacharias C. , Van Der Zanden Martine
Published: October 2010

Science Created by You (SCY) is a project on learning in science and technology domains. SCY uses a pedagogical approach that centres around products, called ‘emerging learning objects’ (ELOs) that are created by students. Students work individually and collaboratively in SCY‐Lab (the general SCY learning environment) on ‘missions’ that are guided by socio‐scientific questions (for example ‘How can we design a CO2‐friendly house?’). Fulfilling SCY missions requires a combination of knowledge from different content areas (eg, physics, mathematics, biology, as well as social sciences). While on a SCY mission, students perform several types of learning activities that can be characterised as productive processes (experiment, game, share, explain, design, etc), they encounter multiple resources, collaborate with varying coalitions of peers and use changing constellations of tools and scaffolds. The configuration of SCY‐Lab is adaptive to the actual learning situation and may provide advice to students on appropriate learning activities, resources, tools and scaffolds, or peer students who can support the learning process. The SCY project aims at students between 12 and 18 years old. In the course of the project, a total of four SCY missions will be developed, of which one is currently available.
A Survey of Ocean Simulation and Rendering Techniques in Computer Graphics
Authors: Darles E. , Crespin B. , Ghazanfarpour D. , Gonzato J.C.
Published: October 2010

This paper presents a survey of ocean simulation and rendering methods in computer graphics. To model and animate the ocean’s surface, these methods mainly rely on two main approaches: on the one hand, those which approximate ocean dynamics with parametric, spectral or hybrid models and use empirical laws from oceanographic research. We will see that this type of methods essentially allows the simulation of ocean scenes in the deep water domain, without breaking waves. On the other hand, physically‐based methods use Navier–Stokes equations to represent breaking waves and more generally ocean surface near the shore. We also describe ocean rendering methods in computer graphics, with a special interest in the simulation of phenomena such as foam and spray, and light’s interaction with the ocean surface.
Heterogeneous and vulnerable: the health risks facing transnational female sex workers
Authors: Choi Susanne Y.P.
Published: October 2010

Representations of transnational sex workers have been dominated by the trafficked victim discourse that often overlooks the heterogeneity of this population and variations in the health risks that different sub‐groups face. This paper addresses this deficiency by examining differences in the socio‐economic backgrounds, working conditions, HIV/AIDS knowledge, and vulnerability to health risks of female sex workers from Russia, Vietnam, Thailand, and Mainland China currently working in the Chinese city of Macau. It also examines the correlates of three health risks: client‐perpetrated violence, non‐condom use and condom failure. The results show major differences in the socio‐economic profiles, working conditions and exposure to health risks of the four groups of workers studied. They also suggest that age, ethnicity, education, economic pressure, AIDS and STI knowledge, and workplace condom‐use norm are significant correlates of the three health risks examined. The findings shed light on the importance of locating the social and cultural contexts that constrain the response of different groups of transnational sex workers to health risks, and the need to tailor intervention measures to meet the specific conditions of individual groups. They also point out the urgency of tackling the interpersonal and structural obstacles to safe sex practices among marginalised populations.
The role of topic, interviewee and question in predicting rich interview data in the field of health research
Authors: Ogden Jane , Cornwell Danielle
Published: October 2010

Although texts recommend the generation of rich data from interviews, no empirical evidence base exists for achieving this. This study aimed to operationalise richness and to assess which components of the interview (for example, topic, interviewee, question) were predictive. A total of 400 interview questions and their corresponding responses were selected from 10 qualitative studies in the area of health identified from university colleagues and the UK Data Archive database. The analysis used the text analysis program, Linguistic Inquiry and Word Count, and additional rating scales. Richness was operationalised along five dimensions. ‘Length of response’ was predicted by a personal, less specific or positive topic, not being a layperson, later questions, open or double questions; ‘personal richness’ was predicted by being a healthy participant and questions about the past and future; ‘analytical responses’ were predicted by a personal or less specific topic, not being a layperson, later questions, questions relating to insight and causation; ‘action responses’ were predicted by a less specific topic, not being a layperson, being healthy, later and open questions. The model for ‘descriptive richness’ was not significant. Overall, open questions, located later on and framed in the present or past tense, tended to be most predictive of richness. This could inform improvements in interview technique.
Survival ofLactobacillus casei,Lactobacillus plantarumandBifidobacterium bifidumin free and microencapsulated forms on Iranian white cheese produced by ultrafiltration
Authors: ZOMORODI SHAHIN , ASL ASGHAR KHOSROWSHAHI , ROHANI SAYAD MAHDI RAZAVI , MIRAGHAEI SOMAYIEH
Published: October 2010

Survival of probiotic strainsLactobacillus casei(ATCC 39392),Lactobacillus plantarum(ATCC 8014) andBifidobacterium bifidum(ATCC 29521) was investigated either in microencapsulated or in free form in the Iranian white cheese produced by ultrafiltration technique. The results indicated that the survival of encapsulated probiotic bacteria was higher than free cells. Both free and microencapsulated forms were successful in keeping counts ofL. casei,L. plantarumandB. bifidumin the cheese high enough for the therapeutic minimum (106–107 cfu/g) after 60 days. Addition of probiotic adjunct also did not alter the chemical composition, but pH was lower in probiotic cheeses.
Prevention of mother‐to‐child transmission of HIV in resource‐rich and ‐poor settings
Authors: Mepham SO , Bland RM , Newell M‐L
Published: October 2010

Please cite this paper as:Mepham S, Bland R, Newell M‐L. Prevention of mother‐to‐child transmission of HIV in resource‐rich and ‐poor settings. BJOG 2011;118:202–218.

Without prevention, a third of HIV‐exposed infants acquire HIV in breastfeeding populations before, during, or after delivery through mother‐to‐child transmission (MTCT). Whereas MTCT is now a sentinel event in resource‐rich countries with antiretroviral prophylaxis, caesarean section, and avoidance of breastfeeding, this is not yet the case in resource‐poor settings because breastfeeding is crucial to infant survival. Recent advances in postpartum maternal and infant prophylaxis enables safer breastfeeding, and increasing numbers of women accessing treatment and prevention of MTCT services in sub‐Saharan Africa is leading to optimism that MTCT could be eliminated here also, as reflected in the UNAIDS target of 2015.
Reduced placental prolyl hydroxylase 3 mRNA expression in pregnancies affected by fetal growth restriction
Authors: Gourvas V , Sifakis S , Dalpa E , Soulitzis N , Koukoura O , Spandidos DA
Published: October 2010

Please cite this paper as: Gourvas V, Sifakis S, Dalpa E, Soulitzis N, Koukoura O, Spandidos D. Reduced placental prolyl hydroxylase 3 mRNA expression in pregnancies affected by fetal growth restriction. BJOG 2010;117:1635–1642.

Objective  To investigate the role of the hypoxia‐inducible factor (HIF) pathway in fetal growth restriction (FGR).

Design  A case–control study.

Setting  Research laboratory and gynaecology clinic.

Sample  Twenty placentas from normal pregnancies and 20 from FGR pregnancies.

Methods  RNA extraction, cDNA synthesis, quantitative real‐time polymerase chain reaction (qRT‐PCR) assay, statistical analysis.

Main outcome measures  mRNA expression of HIF‐1α, HIF‐2α and HIF‐β (ARNT), along with prolyl hydroxylase domain 3 (PHD3), which leads to proteasomal degradation of HIF‐α subunits.

Results  No statistically significant differences in the transcription levels of ARNT and HIF‐2α were found between FGR and normal placentas. By contrast, PHD3 and HIF‐1α mRNA were downregulated in FGR placentas. PHD3 mRNA expression was associated with gestational age at delivery (P = 0.008), birthweight centile (P = 0.029) and abnormal umbilical artery (UA) Doppler measurements (P = 0.034).

Conclusions  As PHD3 regulates the HIF‐mediated hypoxic response in FGR, we deduce that fetal adaptation to hypoxia ranges from impaired to adequate, as observed by the gradient of PHD3 downregulation in relation to the severity of FGR.
Critical illness with AH1N1v influenza in pregnancy: a comparison of two population‐based cohorts
Authors: Knight M , Pierce M , Seppelt I , Kurinczuk JJ , Spark P , Brocklehurst P , McLintock C , Sullivan E ,   on behalf of the UK’s Obstetric Surveillance System, the ANZIC Influenza Investigators, and the Australasian Maternity Outcomes Surveillance System
Published: October 2010

Please cite this paper as: Knight M, Pierce M, Seppelt I, Kurinczuk J, Spark P, Brocklehurst P, McLintock C, Sullivan E, on behalf of the UK’s Obstetric Surveillance System, the ANZIC Influenza Investigators, and the Australasian Maternity Outcomes Surveillance System. Critical illness with AH1N1v influenza in pregnancy: a comparison of two population‐based cohorts. BJOG 2011;118:232–239.

Objective  To compare admissions to intensive care units (ICUs) with confirmed AH1N1v influenza in pregnancy in Australia, New Zealand and the UK.

Design  National cohort studies.

Setting  ICUs in Australia, New Zealand and the UK.

Population  Fifty‐nine women admitted to ICUs in Australia and New Zealand in June–August 2009, and 57 women admitted to ICUs in the UK in September 2009–January 2010.

Methods  Comparison of cohort data.

Main outcome measures  Incidence of ICU admission, comparison of characteristics and outcomes.

Results  There was a significantly higher ICU admission risk in Australia and New Zealand than in the UK (risk ratio 2.59, 95% CI 1.75–3.85). Indigenous women from Australia and women with Maori/Pacific Island backgrounds from New Zealand had the highest admission risk (29.7 admissions per 10 000 maternities, 95% CI 17.9–46.3). Women admitted in Australia and New Zealand were significantly more likely to have a pre‐existing medical condition (51% versus 21%, P = 0.001), but were less likely to receive antiviral treatment (80% versus 93%, P = 0.038) than women admitted in the UK. Women admitted in the UK had a longer length of hospital stay (median 21 days, range 3–128 days) than women admitted in Australia and New Zealand (median 12 days, range 3–66 days), but there were no other differences in maternal or pregnancy outcomes.

Conclusions  The difference in admission risk may reflect a second phase effect from successful clinical and public health interventions, as well as differences in population characteristics between the countries. The overall severity of the AH1N1v influenza infection in pregnancy is evident, and emphasises the importance of an ongoing immunisation programme in pregnant women in both northern and southern hemispheres.
Parvovirus B19 infection in human pregnancy
Authors: Lamont RF , Sobel JD , Vaisbuch E , Kusanovic JP , Mazaki‐Tovi S , Kim SK , Uldbjerg N , Romero R
Published: October 2010

Please cite this paper as: Lamont R, Sobel J, Vaisbuch E, Kusanovic J, Mazaki‐Tovi S, Kim S, Uldbjerg N, Romero R. Parvovirus B19 infection in human pregnancy. BJOG 2011;118:175–186.

Human parvovirus B19 infection is widespread. Approximately 30–50% of pregnant women are nonimmune, and vertical transmission is common following maternal infection in pregnancy. Fetal infection may be associated with a normal outcome, but fetal death may also occur without ultrasound evidence of infectious sequelae. B19 infection should be considered in any case of nonimmune hydrops. Diagnosis is mainly through serology and polymerase chain reaction. Surveillance requires sequential ultrasound and Doppler screening for signs of fetal anaemia, heart failure and hydrops. Immunoglobulins, antiviral and vaccination are not yet available, but intrauterine transfusion in selected cases can be life saving.
Improvement in the nursing care quality in general surgery wards: Iranian nurses’ perceptions
Authors: Molazem Zahra , Ahmadi Fazlollah , Mohammadi Eesa , Bolandparvaz Shahram
Published: October 2010

Scand J Caring Sci; 2011; 25; 350–356
 
Improvement in the nursing care quality in general surgery wards: Iranian nurses’ perceptions

Improving care quality is one of the duties of almost all health service providers. Although it is of much significance to identify the factors influencing nursing care quality in specific clinical settings, a few studies have been conducted to improve our knowledge in this regard. This study aimed to determine Iranian nurses’ perceptions of the factors influencing quality of nursing care in general surgery wards. A qualitative approach was adopted using content analysis of semi‐structured interviews carried out with 15 nurses working in general surgery wards of two educational hospitals. The following themes and subthemes emerged from the analysis: ‘beyond daily routine tasks’, ‘cooperation and the promotion of effective relationship’ and ‘updating education’. The second theme consisted of two subthemes: ‘relationship among care team members’ and ‘communication between nurses, patients and relatives’. Providing qualified nursing care in Iran is complicated contextually and is somehow controversial. The study participants believed that in this context, proper delivery of appropriate nursing care is difficult for nurses owing to the barriers mentioned. Therefore, as a primitive action health care policy makers and managers are required to bring sensible changes into health care system through legislating suitable rules to guarantee the quality of nursing cares.
Health care personnel’s experiences of a bereavement follow‐up intervention for grieving parents
Authors: Liisa Aho Anna , Marja‐Terttu Tarkka , Päivi Åstedt‐Kurki , Marja Kaunonen
Published: October 2010

Scand J Caring Sci; 2011; 25; 373–382
 
Health care personnel’s experiences of a bereavement follow‐up intervention for grieving parents

The aim of this study is to investigate the experiences of health care personnel of a bereavement follow‐up intervention for grieving parents and of the ways to develop it. The intervention included three components: a support package for grieving parents, peer supporters’ and health care personnel’s contact with parents. The sample included 29 health professionals. Data were collected via open‐format questionnaires and telephone interviews from health care personnel. Content analysis was used as a means of data analysis. The support package for grieving parents was considered important and versatile. Health care personnel perceived the intervention and its viability as mostly good. Parents’ willingness to receive support, health care personnel’s good resources and organizational preconditions were important for the follow‐up contact. The intervention clarified the policy related to supporting grieving parents. It was enabled by a good attitude, shift arrangements and co‐worker support. However, the implementation was considered difficult because of scarce resources. Parental support engendered negative feelings in health care personnel and they desired systematic supervision to deal with these. Follow‐up care of grieving parents is a demanding task. Continuous education about bereavement follow‐up care and systematic supervision to health care personnel is needed. Family‐focused care in supporting grieving families after leaving from hospital should be increased. Inter‐organizational cooperation in supporting parents is important and feasible.
Experiential connectedness in children's attachment interviews: An examination of natural word use
Authors: BORELLI JESSICA L. , SBARRA DAVID A. , MEHL MATTHIAS , DAVID DARYN H.
Published: October 2010

Attachment classification derived from narrative analysis is widely used as a marker of psychological organization. In contrast to this top‐down approach, bottom‐up, word count–based analyses of narratives are also used to measure psychological states. The current study integrates these 2 approaches by examining their overlap in 93 school‐aged children. Participants completed the Child Attachment Interview; transcriptions of this interview were subjected to word count–based linguistic analysis. Compared with secure children, dismissing children showed less and preoccupied children showed more signs of experiential connectedness. Disorganized children decreased in experiential connectedness during loss discussions and used more words related to death during nonloss sections of the interview. Results are discussed in terms of their relevance to attachment and relationship research.
Changing relationship growth belief: Intrapersonal and interpersonal consequences of compassionate goals
Authors: CANEVELLO AMY , CROCKER JENNIFER
Published: October 2010

The belief that difficulties can lead to growth in relationships, or growth belief, has consequences for relationships (e.g., C. R. Knee, 1998). But what predicts change in this belief? The current study hypothesized that compassionate goals to support others (J. Crocker & A. Canevello, 2008) predict increased growth belief through increased need satisfaction. In Study 1, 199 college freshmen reported their friendship growth belief and goals. In Study 2, 65 roommate pairs reported their roommate growth belief, goals, and need satisfaction. Across studies, compassionate goals predicted increased growth belief. In Study 2, goals predicted increased perceived mutual need satisfaction, which predicted increased growth belief. Additionally, partners' compassionate goals predicted actors' increased growth belief. Results suggest that growth beliefs are shaped by goals—own and others'.
Identification of a potent anti‐IL‐15 antibody with opposing mechanisms of action in vitro and in vivo
Authors: Finch DK , Midha A , Buchanan CL , Cochrane D , Craggs RI , Cruwys S , Grahames C , Kolbeck R , Lowe DC , Maltby J , Pattison DV , Vousden KA , Ward A , Sleeman MA , Mallinder PR
Published: October 2010

BACKGROUND AND PURPOSE Interleukin‐15 (IL‐15) is important in the activation and proliferation of lymphocytic cell populations and is implicated in inflammatory disease. We report the characterization of a novel monoclonal antibody DISC0280 which is specific for human IL‐15.

EXPERIMENTAL APPROACH DISC0280 was characterized in a direct binding assay of IL‐15 with IL‐15 receptor α (IL‐15Rα) and by its ability to alter IL‐15 mediated proliferation of a range of cell lines (cytotoxic T lymphocyte line‐2, M‐07e, KIT225). A pharmacodynamic model injecting male C57/BL6 mice with IL‐15 or IL‐15/IL‐15Rα, with or without DISC0280, and assessing changes in lymphocytic cell populations and serum cytokines was utilized.

KEY RESULTS DISC0280 inhibited the binding of IL‐15 to IL‐15Rα and also potently inhibits IL‐15 dependent proliferation of cells expressing IL‐15Rα, shared interleukin 2/ interleukin 15 receptor β chain (IL‐15Rβ) and common gamma chain (γc). DISC0280 also inhibited the IL‐15 dependent proliferation of M‐07e cells that only express IL‐15Rβ/γc subunits. Human IL‐15 injected into mice caused an increase in NK1.1+ and CD3+ cells in the spleen and peripheral blood and these effects were unexpectedly potentiated by giving DISC0280 with human IL‐15. This increase in cells caused by DISC0280/IL‐15 co‐administration was greater than that observed when IL‐15 was administered complexed with soluble IL‐15Rα.

CONCLUSIONS AND IMPLICATIONS The ability of DISC0280 to bind to the IL‐15Rα‐binding site on IL‐15 allows trans‐presentation of IL‐15 by DISC0280 in vivo, similar to the trans‐presentation by soluble IL‐15Rα. DISC0280 may be therefore suitable as a clinical substitute for IL‐15.
Bradykinin and B2 receptor antagonism in rat and human articular chondrocytes
Authors: Meini S , Cucchi P , Catalani C , Bellucci F , Giuliani S , Maggi CA
Published: October 2010

BACKGROUND AND PURPOSE

In osteoarthritis (OA), bradykinin (BK) is known to contribute to pain and synovitis, but not to cartilage degradation. Here, we investigated effects of BK and its antagonists on chondrocytes, cells involved in cartilage homeostasis.

EXPERIMENTAL APPROACH

BK receptor density and affinities of BK, its analogues and antagonists were measured in cultured human and rat chondrocytes by radioligand binding. Effects of BK were assessed by accumulation of inositol phosphates (IP) and release of interleukin (IL)‐6 and IL‐8.

KEY RESULTS

Density of [3H]‐BK binding sites was higher (13–30‐fold) and BK evoked a greater (48‐fold) IP production, in human than in rat chondrocytes. The BK B2 receptor antagonists MEN16132 and icatibant displayed similar binding affinity. MEN16132 was 40‐fold more potent than icatibant in the IP assay. In human chondrocytes, BK increased release (over 24 h) of IL‐6 and IL‐8, effects blocked by MEN16132 but not by the B1 receptor antagonist Lys‐[Leu8][desArg9]BK. BK‐induced release of IL‐6, but not of IL‐8, was partially inhibited by indomethacin (10 µM) and nordihydroguaiaretic acid (10 µM). Antagonists for the prostanoid EP receptors (AH6809 10 µM; L‐798 196, 200 nM; L‐161 982, 1 µM) were ineffective. Dexamethasone (100 nM) partially inhibited release of both IL‐6 and IL‐8. Inhibitors of intracellular downstream signalling pathways (SB203580 10 µM; PD98059, 30 µM; SP600125, 30 µM; BAY‐117085, 5 µM) indicated the involvement of p38 MAPK and the activation of NF‐κB.

CONCLUSION AND IMPLICATIONS

BK mediated inflammatory changes and cartilage degradation and B2 receptor blockade would, therefore, be a potential treatment for OA.
Non‐psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action
Authors: Maione Sabatino , Piscitelli Fabiana , Gatta Luisa , Vita Daniela , De Petrocellis Luciano , Palazzo Enza , de Novellis Vito , Di Marzo Vincenzo
Published: October 2010

BACKGROUND AND PURPOSE

Two non‐psychoactive cannabinoids, cannabidiol (CBD) and cannabichromene (CBC), are known to modulate in vitro the activity of proteins involved in nociceptive mechanisms, including transient receptor potential (TRP) channels of vanilloid type‐1 (TRPV1) and of ankyrin type‐1 (TRPA1), the equilibrative nucleoside transporter and proteins facilitating endocannabinoid inactivation. Here we have tested these two cannabinoids on the activity of the descending pathway of antinociception.

EXPERIMENTAL APPROACH

Electrical activity of ON and OFF neurons of the rostral ventromedial medulla in anaesthetized rats was recorded extracellularly and tail flick latencies to thermal stimuli were measured. CBD or CBC along with various antagonists were injected into the ventrolateral periaqueductal grey.

KEY RESULTS

Cannabidiol and CBC dose‐dependently reduced the ongoing activity of ON and OFF neurons in anaesthetized rats, whilst inducing antinociceptive responses in the tail flick‐test. These effects were maximal with 3 nmol CBD and 6 nmol CBC, and were antagonized by selective antagonists of cannabinoid CB1 adenosine A1 and TRPA1, but not of TRPV1, receptors. Both CBC and CBD also significantly elevated endocannabinoid levels in the ventrolateral periaqueductal grey. A specific agonist at TRPA1 channels and a synthetic inhibitor of endocannabinoid cellular reuptake exerted effects similar to those of CBC and CBD.

CONCLUSIONS AND IMPLICATIONS

CBD and CBC stimulated descending pathways of antinociception and caused analgesia by interacting with several target proteins involved in nociceptive control. These compounds might represent useful therapeutic agents with multiple mechanisms of action.
The endoplasmic reticulum protein folding factory and its chaperones: new targets for drug discovery?
Authors: McLaughlin Martin , Vandenbroeck Koen
Published: October 2010

Cytosolic heat shock proteins have received significant attention as emerging therapeutic targets. Much of this excitement has been triggered by the discovery that HSP90 plays a central role in the maintenance and stability of multifarious oncogenic membrane receptors and their resultant tyrosine kinase activity. Numerous studies have dealt with the effects of small molecules on chaperone‐ and stress‐related pathways of the endoplasmic reticulum (ER). However, unlike cytosolic chaperones, relatively little emphasis has been placed upon translational avenues towards targeting of the ER for inhibition of folding/secretion of disease‐promoting proteins. Here, we summarise existing small molecule inhibitors and potential future targets of ER chaperone‐mediated inhibition. Client proteins of translational relevance in disease treatment are outlined, alongside putative future disease treatment modalities based on ER‐centric targeted therapies. Particular attention is paid to cancer and autoimmune disorders via the effects of the GRP94 inhibitor geldanamycin and its population of client proteins, overloading of the unfolded protein response, and inhibition of members of the IL‐12 family of cytokines by celecoxib and non‐coxib analogues.
Vascular KCNQ channels in humans: the sub‐threshold brake that regulates vascular tone?
Authors: Mani Bharath K. , Byron Kenneth L.
Published: October 2010

Contraction of arterial smooth muscle cells results in vasoconstriction, which in turn reduces blood flow and increases blood pressure. There has been a great deal of interest in understanding the ionic mechanisms that regulate smooth muscle contraction, in part because ion channels represent potential pharmacological targets for therapies directed towards cardiovascular diseases and other conditions. Potassium channels have been recognized for their roles in maintaining or stabilizing negative membrane voltages. Activation of potassium channels opposes opening of voltage‐sensitive calcium channels which conduct calcium ions into the smooth muscle cells to stimulate contraction. KCNQ potassium channels were recently discovered in arterial smooth muscle cells from rats and mice. These channels have distinctive pharmacological and biophysical characteristics that have led them to be implicated as important regulators of membrane voltage and as novel pharmacological targets for modulation of vascular contractility. In this issue of British Journal of Pharmacology, Ng et al., extend the findings from rodent models to the human vasculature and establish that KCNQ channels also regulate constriction of human arteries. The findings have important implications for the use of pharmacological KCNQ channel modulators to treat human diseases.

LINKED ARTICLE This article is a commentary on Ng et al., pp. 42–53 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476‐5381.2010.01027.x
cAMP‐ and Ca2+/calmodulin‐dependent protein kinases mediate inotropic, lusitropic and arrhythmogenic effects of urocortin 2 in mouse ventricular myocytes
Authors: Yang Li‐Zhen , Kockskämper Jens , Khan Shelina , Suarez Jorge , Walther Stefanie , Doleschal Bernhard , Unterer Gregor , Khafaga Mounir , Mächler Heinrich , Heinzel Frank R. , Dillmann Wolfgang H. , Pieske Burkert , Spiess Joachim
Published: October 2010

BACKGROUND AND PURPOSE Urocortin 2 is beneficial in heart failure, but the underlying cellular mechanisms are not completely understood. Here we have characterized the functional effects of urocortin 2 on mouse cardiomyocytes and elucidated the underlying signalling pathways and mechanisms.

EXPERIMENTAL APPROACH Mouse ventricular myocytes were field‐stimulated at 0.5 Hz at room temperature. Fractional shortening and [Ca2+]i transients were measured by an edge detection and epifluorescence system respectively. Western blots were carried out on myocyte extracts with antibodies against total phospholamban (PLN) and PLN phosphorylated at serine‐16.

KEY RESULTS Urocortin 2 elicited time‐ and concentration‐dependent positive inotropic and lusitropic effects (EC50: 19 nM) that were abolished by antisauvagine‐30 (10 nM, n= 6), a specific antagonist of corticotrophin releasing factor (CRF) CRF2 receptors. Urocortin 2 (100 nM) increased the amplitude and decreased the time constant of decay of the underlying [Ca2+]i transients. Urocortin 2 also increased PLN phosphorylation at serine‐16. H89 (2 µM) or KT5720 (1 µM), two inhibitors of protein kinase A (PKA), as well as KN93 (1 µM), an inhibitor of Ca2+/calmodulin‐dependent protein kinase II (CaMKII), suppressed the urocortin 2 effects on shortening and [Ca2+]i transients. In addition, urocortin 2 also elicited arrhythmogenic events consisting of extra cell shortenings and extra [Ca2+]i increases in diastole. Urocortin 2‐induced arrhythmogenic events were significantly reduced in cells pretreated with KT5720 or KN93.

CONCLUSIONS AND IMPLICATIONS Urocortin 2 enhanced contractility in mouse ventricular myocytes via activation of CRF2 receptors in a cAMP/PKA‐ and Ca2+/CaMKII‐dependent manner. This enhancement was accompanied by Ca2+‐dependent arrhythmogenic effects mediated by PKA and CaMKII.
Byakangelicin induces cytochrome P450 3A4 expression via transactivation of pregnane X receptors in human hepatocytes
Authors: Yang Jian , Luan Xiaofei , Gui Haiyan , Yan Peng , Yang Dongfang , Song Xiulong , Liu Wei , Hu Gang , Yan Bingfang
Published: October 2010

BACKGROUND AND PURPOSEByakangelicin is found in extracts of the root ofAngelica dahurica, used in Korea and China as a traditional medicine to treat colds, headache and toothache. As byakangelicin can inhibit the effects of sex hormones, it may increase the catabolism of endogenous hormones. Therefore, this study investigated the effects of byakangelicin on the cytochrome P450 isoform cytochrome (CY) P3A4 in human hepatocytes.

EXPERIMENTAL APPROACHCultures of human hepatocytes and a hepatoma cell line (Huh7 cells) were used. mRNA and protein levels were measured by quantitative reverse transcription‐polymerase chain reaction and Western blot. Plasmid constructs and mutants were prepared by cloning and site‐directed mutagenesis. Reporter (luciferase) activity was determined by transient co‐transfection experiments.

KEY RESULTSIn human primary hepatocytes, byakangelicin markedly induced the expression of CYP3A4 both at the mRNA level (approximately fivefold) and the protein level (approximately threefold) but did not affect expression of human pregnane X receptor (hPXR). In reporter assays, byakangelicin activated CYP3A4 promoter in a concentration‐dependent manner (EC50= 5 µM), and this activation was enhanced by co‐transfection with hPXR. Further reporter assays demonstrated that the eNR4 binding element in the CYP3A4 promoter was required for the transcriptional activation of CYP3A4 by byakangelicin.

CONCLUSIONS AND IMPLICATIONSByakangelicin induced expression and activity of CYP3A4 in human hepatocytes. This induction was achieved by the transactivation of PXR and not by increased expression of PXR. Therefore, byakangelicin is likely to increase the expression of all PXR target genes (such as MDR1) and induce a wide range of drug–drug interactions.
Scutellarin alleviates interstitial fibrosis and cardiac dysfunction of infarct rats by inhibiting TGFβ1 expression and activation of p38‐MAPK and ERK1/2
Authors: Pan Zhenwei , Zhao Weiming , Zhang Xiangying , Wang Bing , Wang Jinghao , Sun Xuelin , Liu Xuantong , Feng Shuya , Yang Baofeng , Lu Yanjie
Published: October 2010

BACKGROUND AND PURPOSE

Interstitial fibrosis plays a causal role in the development of heart failure after chronic myocardial infarction (MI), and anti‐fibrotic therapy represents a promising strategy to mitigate this pathological process. The purpose of this study was to investigate the effect of long‐term administration of scutellarin (Scu) on cardiac interstitial fibrosis of myocardial infarct rats and the underlying mechanisms.

EXPERIMENTAL APPROACH

Scu was administered to rats that were subjected to coronary artery ligation. Eight weeks later, its effects on cardiac fibrosis were assessed by examining cardiac function and histology. The number and collagen content of cultured cardiac fibroblasts exposed to angiotensin II (Ang II) were determined after the administration of Scu in vitro. Protein expression was detected by Western blot technique, and mRNA levels by quantitative reverse transcription‐PCR.

KEY RESULTS

The echocardiographic and haemodynamic measurements showed that Scu improved the impaired cardiac function of infarct rats and decreased interstitial fibrosis. Scu inhibited the expression of FN1 and TGFβ1, but produced no effects on inflammatory cytokines (TNFα, IL‐1β and IL‐6) in the 8 week infarct hearts. Scu inhibited the proliferation and collagen production of cardiac fibroblasts (CFs) and the up‐regulation of FN1 and TGFβ1 induced by Ang II. The enhanced phosphorylation of p38‐MAPK and ERK1/2 in both infarct cardiac tissue and cultured CFs challenged by Ang II were suppressed by Scu.

CONCLUSIONS AND IMPLICATIONS

Long‐term administration of Scu improved the cardiac function of MI rats by inhibiting interstitial fibrosis, and the mechanisms may involve the suppression of pro‐fibrotic cytokine TGFβ1 expression and inhibition of p38 MAPK and ERK1/2 phosphorylation.
Disulphide trapping of the GABAA receptor reveals the importance of the coupling interface in the action of benzodiazepines
Authors: Hanson Susan M. , Czajkowski Cynthia
Published: October 2010

BACKGROUND AND SIGNIFICANCE

Although the functional effects of benzodiazepines (BZDs) on GABAA receptors have been well characterized, the structural mechanism by which these modulators alter activation of the receptor by GABA is still undefined.

EXPERIMENTAL APPROACH

We used disulphide trapping between engineered cysteines to probe BZD‐induced conformational changes within the γ2 subunit and at the α1/γ2 coupling interface (Loops 2, 7 and 9) of α1β2γ2 GABAA receptors.

KEY RESULTS

Crosslinking γ2Loop 9 to γ2β‐strand 9 (via γ2S195C/F203C and γ2S187C/L206C) significantly decreased maximum potentiation by flurazepam, suggesting that modulation of GABA‐induced current (IGABA) by flurazepam involves movements of γ2Loop 9 relative to γ2β‐strand 9. In contrast, tethering γ2β‐strand 9 to the γ2 pre‐M1 region (via γ2S202C/S230C) significantly enhanced potentiation by both flurazepam and zolpidem, indicating γ2S202C/S230C trapped the receptor in a more favourable conformation for positive modulation by BZDs. Intersubunit disulphide bonds formed at the α/γ coupling interface between α1Loop 2 and γ2Loop 9 (α1D56C/γ2L198C) prevented flurazepam and zolpidem from efficiently modulating IGABA. Disulphide trapping α1Loop 2 (α1D56C) to γ2β‐strand 1 (γ2P64C) decreased maximal IGABA as well as flurazepam potentiation. None of the disulphide bonds affected the ability of the negative modulator, 3‐carbomethoxy‐4‐ethyl‐6,7‐dimethoxy‐β‐carboline (DMCM), to inhibit IGABA.

CONCLUSIONS AND IMPLICATIONS

Positive modulation of GABAA receptors by BZDs requires reorganization of the loops in the α1/γ2 coupling interface. BZD‐induced movements at the α/γ coupling interface likely synergize with rearrangements induced by GABA binding at the β/α subunit interfaces to enhance channel activation by GABA.
Individualizing treatment duration in hepatitis C virus genotype 2/3‐infected patients
Authors: Mangia Alessandra
Published: October 2010

The drugs currently licensed for the treatment of hepatitis C are Peg‐Interferon (PEG‐IFN) and ribavirin. In recent years, the recommendation to treat hepatitis C virus genotype 2‐ and 3‐infected patients with a fixed 800 mg/day dose of ribavirin in combination with PEG‐IFN and for just 24 weeks has been challenged by the concept of tailoring the length of therapy according to on‐treatment viral response. Therefore, the objective of the present review was to highlight the different designs of the studies on short treatment duration and the role of wk4‐R as a predictor of sustained virological response after an abbreviated course of treatment. The secondary aim was to verify whether we had enough evidence to support the implementation of a short treatment course in subsets of patients with genotype 2 and 3 infection. We will also focus on how drug dosing may have influenced the outcome of treatment. To clarify reasons for discrepant results in the studies so far published, the recently discovered genetic variant near the interleukin 28B gene will be presented and its predictive role will be discussed. Finally, we will face the debated issue of whether the subset of patients with genotype 2 or 3 requires an extended treatment duration.
Managing Innovation Fields in a Cross‐Industry Exploratory Partnership with C–K Design Theory*
Authors: Gillier Thomas , Piat Gerald , Roussel Benoît , Truchot Patrick
Published: October 2010

For a few decades now, firms have had to innovate in cooperation with other organizations. According to the literature on co‐innovation, a new form of innovation partnership is now emerging: the exploratory partnership. This type of partnership is the most often established in the early stages of the design process and faces high levels of uncertainty and instability. This paper deals with a strategic design tool, OPERA, based on a recent general design theory named C–K theory. That theory models design reasoning by suggesting a fundamental distinction between concepts (propositions about novel objects) and knowledge (propositions about known objects). According to the theory, the interaction and co‐evolution of concepts and knowledge is the main engine through which design progresses. The paper proposes to extend that theory to understand and to act in innovation community context. OPERA enables power holders and design teams to drive innovation projects by providing them with an overview of explored and unexplored concepts and of the activation and production of skills and knowledge. This cartographic system was tested by MINATEC IDEAs Laboratory, a Cross‐Industry Exploratory Partnership, over a 15‐month period. The innovative platform is composed of partners from different sectors (e.g., energy, technology research center, sports, telecommunications) and aims to build innovative projects and to devise new products and services based on micronanotechnologies. Facing such diversities, actors of MINATEC IDEAs Laboratory used OPERA to see how each project is progressing, the contribution of each project to the global exploration process, and the complementarities between the projects. Such representations enable the committee to identify the main value of a project, any knowledge gaps and the synergies between projects. From a collective point of view, OPERA permits to MINATEC IDEAs Laboratory's members to indicate their favorite concepts and knowledge areas and to estimate converging and diverging interests.