bluuebunny/crossref_metadata_2025 huggingface dataset:
TRUST AS A TRADABLE COMMODITY: A FOUNDATION FOR SAFE ELECTRONIC MARKETPLACES
Authors: Kerr Reid , Cohen Robin
Published: April 2010

In large electronic marketplaces populated by buying and selling agents, it is difficult to judge trustworthiness. A variety of systems have been proposed to help traders to find trustworthy partners by learning to discount or disregard disreputable parties. In this article, we present a novel model for providing safe electronic marketplaces: Commodity Trunits, a system that considers trust as a tradable commodity. In this system, sellers require units of trust (trunits) to participate in transactions, and risk losing trunits if they act dishonestly. Sellers can purchase trunits when needed, and sell excess quantities. We demonstrate that under Commodity Trunits, rational sellers will choose to be honest, since this is the profit maximizing strategy. We also show that Commodity Trunits provides protection from a number of vulnerabilities common in existing trust and reputation systems, e.g., the important exit problem, where sellers can cheat without fear of repercussions if they intend to leave the market. We then present a simulation that validates the system by demonstrating that a market operator can manage the trunit marketplace to ensure sustainability. We conclude with a discussion of the value of Commodity Trunits as a method for promoting trust in electronic marketplaces.
DRAMA MANAGEMENT AND PLAYER MODELING FOR INTERACTIVE FICTION GAMES
Authors: Sharma Manu , Ontañón Santiago , Mehta Manish , Ram Ashwin
Published: April 2010

A growing research community is working toward employing drama management components in story‐based games. These components gently guide the story toward a narrative arc that improves the player's gaming experience. In this article we evaluate a novel drama management approach deployed in an interactive fiction game called Anchorhead. This approach uses player's feedback as the basis for guiding the personalization of the interaction. The results indicate that adding our Case‐based Drama manaGer (C‐DraGer) to the game guides the players through the interaction and provides a better overall player experience. Unlike previous approaches to drama management, this article focuses on exhibiting the success of our approach by evaluating results using human players in a real game implementation. Based on this work, we report several insights on drama management which were possible only due to an evaluation with real players.
Gender Cultures and the Division of Labour in Contemporary Europe: A Cross-National Perspective
Authors: Aboim Sofia
Published: April 2010

Drawing on the vast literature concerned with the cultural aspects of gender, this article explores the ways in which individuals living in different national contexts value the ideal of a dual earner/dual carer couple at the expense of the male breadwinner model. Via a comparison of fifteen European countries included in the Family and Gender Roles module of the 2002 International Social Survey Programme (ISSP), three attitudinal patterns were identified: the unequal sharing that portrays a male breadwinner norm, the familistic unequal that also endorses a gender-segregated arrangement though with a greater wish for men's involvement in housework and childcare, and the dual earner/dual carer model, which, despite covering nearly 40 per cent of respondents, is very unequally distributed across countries. It is proposed that societal gender cultures are of major importance to an understanding of cross-national variations in attitudes and their relationship with the real forms of gender division of labour. The connection between couples' attitudes and practices is thus examined in order to assess the extent to which support for the dual earner/dual carer model encourages couples to engage in more equal sharing of paid and unpaid work. Findings reveal the importance of the normative dimension insofar as the impact of attitudes on practices seems to depend on the historical pathways of gender cultures and the ways in which they underpin welfare policies and female employment.
Feeling Special: Language in the Lives of Polish People
Authors: Temple Bogusia
Published: April 2010

In this article I use findings from an ESRC funded project on language and identity in the narratives of Polish people to challenge a narrow approach to language in debates about integration. I argue that decisions about learning languages are influenced by wider concerns of self and other identification rather then simply being issues of instrumental need. I show how research participants viewed speaking Polish as an important part of being Polish, that is, of their identity. They recognised that changing the language they spoke involved questioning the way they presented themselves and how they related to others. I discuss how language was used to differentiate between ‘us’ and ‘others’, including in terms of values and the ways in which these perceptions of difference influenced social interactions.
Social Change and Selectionist Thought: On Spencer, Darwin and Runciman
Authors: Offer John
Published: April 2010

Deep divisions persist within sociology over the potential of a neo-Darwinian selectionist paradigm of explanation to contribute positively to social theory and research. Herbert Spencer's concern with the progressive direction of evolution, and uncertainty about the divergences between Darwinian and Spencerian thought over ‘natural selection’ and the ‘survival of the fittest’, often freight preconceptions of the potential of the paradigm. This article first explains how ideas primarily attributable to Spencer rather than Darwin have served to cloud the debate. It thus clarifies Spencer's ideas on evolutionary process, disentangling them from and establishing their marginality to Darwin's central concerns. Second, it considers recent work by Runciman on selectionism and change in Britain, and suggests that the usefulness of adopting a selectionist paradigm need not (yet) involve a quasi-genetic unit of change as a component: novel ‘variations’, with some and not other practices ‘selected’ over time, may suffice. Third, it considers with examples, including Goffman on ‘stigma’ and the decline of the poor law, the new questions opened up for social theory by this modestly selectionist mode of analysis. It also discusses how recent work from neo-Darwinian, biologically-based researchers in the field of gene-culture coevolution is proving, in a complementary way, innovative in its conceptualisation of the central role of agency in social life.
Analysis of RET, ZEB2, EDN3 and GDNF Genomic Rearrangements in Central Congenital Hyperventilation Syndrome Patients by Multiplex Ligation‐dependent Probe Amplification
Authors: Serra Alexandre , Görgens Heike , Alhadad Karin , Fitze Guido , Schackert Hans K.
Published: April 2010

Central congenital hypoventilation syndrome (CCHS) is an autonomous control disease producing hypoventilation, high PaCO2, and low PaO2 during quiet sleep. The main gene variants detected in CCHS are mutations in the PHOX2b gene in up to 97% of isolated cases. However, CCHS is sometimes associated with autonomic diseases such as Hirschsprung disease (HSCR). Since genomic rearrangements in particularly sensitive areas of the RET protooncogene and/or associated genes may account for the CCHS/HSCR phenotype in patients without other detectable RET variants, the aim of the present study was to identify rearrangements in the coding sequence of RET as well as in three HSCR‐associated genes (ZEB2, EDN3 and GDNF) in CCHS/HSCR patients by using Multiplex Ligation‐dependent Probe Amplification (MLPA). We have screened 27 CCHS and 11 CCHS/HSCR patients for genomic rearrangements in RET, ZEB2, EDN3 and GDNF and did not identify any deletion or amplification in these four genes in all patients. We conclude that genomic rearrangements in RET are rare and were not responsible for the CCHS/HSCR phenotype in individuals without identifiable germline RET variants in our group of patients, yet this possibility cannot be excluded altogether given the size of the cohort.
A longitudinal investigation of early reading and language skills in children with poor reading comprehension
Authors: Nation Kate , Cocksey Joanne , Taylor Jo S.H. , Bishop Dorothy V.M.
Published: April 2010

Background:  Poor comprehenders have difficulty comprehending connected text, despite having age‐appropriate levels of reading accuracy and fluency. We used a longitudinal design to examine earlier reading and language skills in children identified as poor comprehenders in mid‐childhood.

Method:  Two hundred and forty‐two children began the study at age 5. Further assessments of language and reading skill were made at 5.5, 6, 7 and 8 years. At age 8, fifteen children met criteria for being a poor comprehender and were compared to 15 control children both concurrently and prospectively.

Results:  Poor comprehenders showed normal reading accuracy and fluency at all ages. Reading comprehension was poor at each time point and, notably, showed minimal increases in raw score between 6 and 8 years. Phonological skills were generally normal throughout, but mild impairments in expressive and receptive language, listening comprehension and grammatical understanding were seen at all ages.

Conclusions:  Children identified as poor comprehenders at 8 years showed the same reading profile throughout earlier development. Their difficulties with the non‐phonological aspects of oral language were present at school entry and persisted through childhood, showing that the oral language weaknesses seen in poor comprehenders in mid‐childhood are not a simple consequence of their reading comprehension impairment.
Attentional networks in children and adolescents with autism spectrum disorder
Authors: Keehn Brandon , Lincoln Alan J. , Müller Ralph‐Axel , Townsend Jeanne
Published: April 2010

Background:  Individuals diagnosed with autism spectrum disorder (ASD) exhibit lifelong abnormalities in the adaptive allocation of visual attention. The ubiquitous nature of attentional impairments in ASD has led some authors to hypothesize that atypical attentional modulation may be a factor in the development of higher‐level sociocommunicative deficits.

Method:  Participants were 20 children with ASD and 20 age‐ and Nonverbal IQ‐matched typically developing (TD) children. We used the Attention Network Test (ANT) to investigate the efficiency and independence of three discrete attentional networks: alerting, orienting, and executive control. Additionally, we sought to investigate the relationship between each attentional network and measures of sociocommunicative symptom severity in children with ASD.

Results:  Results indicate that the orienting, but not alerting or executive control, networks may be impaired in children with ASD. In contrast to TD children, correlational analyses suggest that the alerting and executive control networks may not function as independently in children with ASD. Additionally, an association was found between the alerting network and social impairment and between the executive control network and IQ in children with ASD.

Conclusions:  The results provide further evidence of an impairment in the visuospatial orienting network in ASD and suggest that there may be greater interdependence of alerting and executive control networks in ASD. Furthermore, decreased ability to efficiently modulate levels of alertness was related to increased sociocommunicative deficits, suggesting that domain‐general attentional function may be associated with ASD symptomatology.
ARCHAEOMAGNETIC DATING OF COPPER SMELTING SITE F2 IN THE TIMNA VALLEY (ISRAEL) AND ITS IMPLICATIONS FOR THE MODELLING OF ANCIENT TECHNOLOGICAL DEVELOPMENTS
Authors: BEN‐YOSEF E. , TAUXE L. , LEVY T. E.
Published: April 2010

Site F2 in the Timna Valley, Israel, is a small copper smelting site of ‘primitive’ technology, dated by its excavator to the Pottery Neolithic (sixth to fifth millennium bce). This early date challenges the common view of the beginning of smelting technology in the Levant and has been contested by various scholars since its publication. In this study, we present results of archaeointensity experiments conducted on slag fragments from the site. The slag yielded an excellent ancient geomagnetic value (64.1 ± 1.1 μT) that, when compared to the Levantine master curve, suggests an age not older than the second millennium and most probably between the 13th and 11th centuries bce. In addition to demonstrating the applicability of geomagnetic archaeointensity experiments to independent dating of slag, we discuss the implications of the current results for the socio‐historical picture of the Timna Valley, and in particular for the way in which technological developments were previously modelled in the archaeometallurgical research on the region.
A quest for sustainability: Brazil nut gatherers of São Francisco do Iratapuru and the Natura Corporation
Authors: LE TOURNEAU FRANÇOIS‐MICHEL , GREISSING ANNA
Published: April 2010

The Iratapuru Sustainable Development Reserve is mainly exploited by the community of São Francisco village. To improve their standard of living, this village organised its members around a production co‐operative in 1992. Following considerable support from local and international institutions, this community became a symbol of sustainable development projects for ‘traditional’ communities of the Amazon. This was even more so after 2004, when an innovative partnership was established between the Brazilian cosmetics company NATURA and the village of São Francisco. Although the company claims that it associates its own economic interests with the priorities of the community, a number of questions arise nonetheless around this community–company deal, which our study tries to address. To that end, we first present the Jarí region and describe the Brazil nut production process in Iratapuru. Subsequently we give an overview of the development efforts in Iratapuru since the 1990s, focusing on the recent experience with NATURA. In the last part we analyse the NATURA–São Francisco relationship as a special case of a community–company deal in the Amazon.
The impact of eighteenth century earthquakes on the Algarve region, southern Portugal
Authors: CHESTER DAVID K , CHESTER OLIVIA K
Published: April 2010

In the eighteenth century the Algarve was affected by two large and destructive earthquakes. The first occurred in 1722, had an estimated magnitude of between 6.5 and 7.8 Mw and severely affected the coastal zone of the central Algarve. Thirty three years later in 1755 the ‘Lisbon earthquake’ (magnitude c. 8.5 Mw) killed around 12 000 people in Portugal, of whom just over 1000 lived in the Algarve. With an estimated cost of between 32 and 48% of Portugal's gross national product, in financial terms it is the greatest natural disaster to have affected western Europe and its effects on the Algarve, the region closest to the epicentre, were devastating. Using data collected in the field together with archival materials the authors discuss: the economic and social impacts of these two eighteenth century earthquakes and their associated tsunamis on the Algarve; and recovery of the region in the years that followed. Today the Algarve is a major European tourist destination with a resident population of c.430 000, a figure which almost doubles at the height of the tourist season. The 1722 and 1755 earthquakes were not isolated events, but part of a long and destructive seismic history, and today the region is highly exposed to the effects of future earthquakes and tsunamis. The paper concludes with a discussion of current attempts being made by the Portuguese authorities to reduce hazard exposure by means of building codes, the production of hazard maps and emergency plans. In these plans a 1755 type event is viewed as a worst‐case scenario, although because of its epicentral location near to the economic heart of the region and in spite of its smaller size, a 1722 type event would be far more destructive.
MEASURING INEQUALITIES: DO HOUSEHOLD SURVEYS PAINT A REALISTIC PICTURE?
Authors: Guénard Charlotte , Mesplé‐Somps Sandrine
Published: April 2010

The paper addresses the issue of the accuracy of standard‐of‐living measurements using household survey data. First, it highlights the fact that lighter data collection processes in some developing countries have added to measurement errors in consumption and income aggregates measurement errors. The paper reasserts the need to apply reference guidelines to the measurement of household consumption in order to compute comparable distribution indicators across countries and over time. Second, it contends that it is hard to analyze inequality solely from consumption patterns without taking income and savings into account. Two solutions are proposed for the correction of income measurement errors: by using savings declarations and by implementing a multiple imputation procedure. The results are based on a careful analysis of the EPM93 survey of Madagascar whose design is quite close to the LSMS household surveys, and the ENV98 survey of Côte d'Ivoire representative of surveys conducted nowadays in most Sub‐Saharan African countries.
A novel antagonist of the prostaglandin E2 EP4 receptor inhibits Th1 differentiation and Th17 expansion and is orally active in arthritis models
Authors: Chen Q , Muramoto K , Masaaki N , Ding Y , Yang H , Mackey M , Li W , Inoue Y , Ackermann K , Shirota H , Matsumoto I , Spyvee M , Schiller S , Sumida T , Gusovsky F , Lamphier M
Published: April 2010

Background and purpose:  Rheumatoid arthritis (RA) is an autoimmune disorder involving subsets of activated T cells, in particular T helper (Th) 1 and Th17 cells, which infiltrate and damage tissues and induce inflammation. Prostaglandin E2 (PGE2) enhances the Th17 response, exacerbates collagen‐induced arthritis (CIA) and promotes inflammatory pain. The current study investigated whether selective antagonism of the PGE2 EP4 receptor would suppress Th1/Th17 cell development and inflammatory arthritis in animal models of RA.

Experimental approach:  Effects of PGE2 and a novel EP4 receptor antagonist ER‐819762 on Th1 differentiation, interleukin‐23 (IL‐23) production by dendritic cells (DCs), and Th17 development were assessed in vitro. The effect of ER‐819762 was evaluated in CIA and glucose‐6‐phosphate isomerase (GPI)‐induced arthritis models. In addition, the effects of ER‐819762 on pain were evaluated in a model of chronic inflammatory pain induced by complete Freund's adjuvant (CFA) in the rat.

Key results:  Stimulation of the EP4 receptor enhanced Th1 differentiation via phosphatidylinositol 3 kinase signalling, selectively promoted Th17 cell expansion, and induced IL‐23 secretion by activated DCs, effects suppressed by ER‐819762 or anti‐PGE2 antibody. Oral administration of ER‐19762 suppressed Th1 and Th17 cytokine production, suppressed disease in collagen‐ and GPI‐induced arthritis in mice, and suppressed CFA‐induced inflammatory pain in rats.

Conclusion and implications:  PGE2 stimulates EP4 receptors to promote Th1 differentiation and Th17 expansion and is critically involved in development of arthritis in two animal models. Selective suppression of EP4 receptor signalling may have therapeutic value in RA both by modifying inflammatory arthritis and by relieving pain.
Spinal glial TLR4‐mediated nociception and production of prostaglandin E2and TNF
Authors: Saito O , Svensson CI , Buczynski MW , Wegner K , Hua X‐Y , Codeluppi S , Schaloske RH , Deems RA , Dennis EA , Yaksh TL
Published: April 2010

Background and purpose: Toll‐like receptor 4 (TLR4) expressed on spinal microglia and astrocytes has been suggested to play an important role in the regulation of pain signalling. The purpose of the present work was to examine the links between TLR4, glial activation and spinal release of prostaglandin E2(PGE2) and tumour necrosis factor (TNF), and the role these factors play in TLR4‐induced tactile allodynia.

Experimental approach: Toll‐like receptor 4 was activated by intrathecal (i.t.) injection of lipopolysaccharide (LPS) and KDO2‐Lipid A (KDO2) to rats. Tactile allodynia was assessed using von Frey filaments and cerebrospinal fluid collected through spinal dialysis and lumbar puncture. PGE2and TNF levels were measured by mass spectometry andelisa. Minocycline and pentoxifylline (glia inhibitors), etanercept (TNF‐blocker) and ketorolac (COX‐inhibitor) were given i.t. prior to injection of the TLR4‐agonists, in order to determine if these agents alter TLR4‐mediated nociception and the spinal release of PGE2and TNF.

Key results: Spinal administration of LPS and KDO2produced a dose‐dependent tactile allodynia, which was attenuated by pentoxifylline, minocycline and etanercept but not ketorolac. Both TLR4 agonists induced the spinal release of PGE2and TNF. Intrathecal pentoxifylline blunted PGE2and TNF release, while i.t. minocycline only prevented the spinal release of TNF. The release of PGE2induced by LPS and KDO2was attenuated by i.t. administration of ketorolac.

Conclusions and implications: Activation of TLR4 induces tactile allodynia, which is probably mediated by TNF released by activated spinal glia.
Acute activation of eNOS by statins involves scavenger receptor‐B1, G protein subunit Gi, phospholipase C and calcium influx
Authors: Datar R , Kaesemeyer WH , Chandra S , Fulton DJ , Caldwell RW
Published: April 2010

Background and purpose:  Statins (HMG CoA reductase inhibitors) have beneficial effects independent of reducing cholesterol synthesis and this includes their ability to acutely activate endothelial nitric oxide synthase (eNOS). The mechanism by which this occurs is largely unknown and thus we characterized the pathways by which statins activate NOS, including involvement of scavenger receptor‐B1 (SR‐B1), which is expressed in endothelial cells and maintains cholesterol concentrations.

Experimental approach:  Nitric oxide production was monitored in bovine aortic endothelial cells (BAECs) exposed to lovastatin (LOV) or pravastatin (PRA) for 10–20 min, alone or following pre‐exposure to the end product of HMG‐CoA reductase (mevalonate), G protein inhibitors (pertussis/cholera toxins), phospholipase C (PLC) inhibitor (U‐73122), or intracellular and extracellular calcium chelators – BAPTA‐AM and EGTA (respectively), or a function blocking antibody to SR‐B1.

Key results:  Both statins increased NO production in a rapid, dose‐dependent and HMG‐CoA reductase‐independent manner. Inhibiting Gi protein or PLC almost completely blocked statin‐induced NO generation. Additionally, removing extracellular calcium inhibited statin‐induced NO production. COS‐7 cells co‐transfected with eNOS and SR‐B1 increased NO production when exposed to LOV or high‐density lipoprotein (HDL), an agonist of SR‐B1. These effects were not observed in COS‐7 cells with eNOS alone or co‐transfected with bradykinin receptor 2, indicating specificity for SR‐B1. Further, pretreatment of BAEC with blocking antibody for SR‐B1 blocked NO responses to statins and HDL.

Conclusions and implications:  LOV and PRA acutely activate eNOS through pathways that include the cell surface receptor SR‐B1, Gi protein, phosholipase C and entry of extracellular calcium into endothelial cells.
Depression‐resistant endophenotype in mice overexpressing cannabinoid CB2 receptors
Authors: García‐Gutiérrez MS , Pérez‐Ortiz JM , Gutiérrez‐Adán A , Manzanares J
Published: April 2010

Background and purpose:  The present study evaluated the role of CB2 receptors in the regulation of depressive‐like behaviours. Transgenic mice overexpressing the CB2 receptor (CB2xP) were challenged with different types of acute and chronic experimental paradigms to evaluate their response in terms of depressive‐like behaviours.

Experimental approach:  Tail suspension test (TST), novelty‐suppressed feeding test (NSFT) and unpredictable chronic mild stress tests (CMS) were carried out in CB2xP mice. Furthermore, acute and chronic antidepressant‐like effects of the CB2 receptor‐antagonist AM630 were evaluated by means of the forced swimming test (FST) and CMS, respectively, in wild‐type (WT) and CB2xP mice. CB2 gene expression, brain‐derived neurotrophic factor (BDNF) gene and protein expressions were studied in mice exposed to CMS by real‐time PCR and immunohistochemistry, respectively.

Key results:  Overexpression of CB2 receptors resulted in decreased depressive‐like behaviours in the TST and NSFT. CMS failed to alter the TST and sucrose consumption in CB2xP mice. In addition, no changes in BDNF gene and protein expression were observed in stressed CB2xP mice. Interestingly, acute administration of AM630 (1 and 3 mg·kg−1, i.p.) exerted antidepressant‐like effects on the FST in WT, but not in CB2xP mice. Chronic administration of AM630 for 4 weeks (1 mg·kg−1; twice daily, i.p.) blocked the effects of CMS on TST, sucrose intake, CB2 receptor gene, BDNF gene and protein expression in WT mice.

Conclusion and implications:  Taken together, these results suggest that increased CB2 receptor expression significantly reduced depressive‐related behaviours and that the CB2 receptor could be a new potential therapeutic target for depressive‐related disorders.
Symptomatic and neuroprotective effects following activation of nigral group III metabotropic glutamate receptors in rodent models of Parkinson's disease
Authors: Austin PJ , Betts MJ , Broadstock M , O'Neill MJ , Mitchell SN , Duty S
Published: April 2010

Background and purpose:  Increased glutamatergic innervation of the substantia nigra pars reticulata (SNpr) and pars compacta (SNpc) may contribute to the motor deficits and neurodegeneration, respectively, in Parkinson's disease (PD). This study aimed to establish whether activation of pre‐synaptic group III metabotropic glutamate (mGlu) receptors reduced glutamate release in the SN, and provided symptomatic or neuroprotective relief in animal models of PD.

Experimental approach:  Broad‐spectrum group III mGlu receptor agonists, O‐phospho‐l‐serine (l‐SOP) and l‐2‐amino‐4‐phosphonobutyrate (l‐AP4), were assessed for their ability to inhibit KCl‐evoked [3H]‐d‐aspartate release in rat nigral prisms or inhibit KCl‐evoked endogenous glutamate release in the SNpr in vivo using microdialysis. Reversal of akinesia in reserpine‐treated rats was assessed following intranigral injection of l‐SOP and l‐AP4. Finally, the neuroprotective effect of 7 days' supra‐nigral treatment with l‐AP4 was examined in 6‐hydroxydopamine (6‐OHDA)‐lesioned rats.

Key results:  l‐SOP and l‐AP4 inhibited [3H]‐d‐aspartate release by 33 and 44% respectively. These effects were blocked by the selective group III mGlu antagonist (RS)‐α‐cyclopropyl‐4‐phosphonophenylglycine (CPPG). l‐SOP also reduced glutamate release in the SNpr in vivo by 48%. Injection of l‐SOP and l‐AP4 into the SNpr reversed reserpine‐induced akinesia. Following administration above the SNpc, l‐AP4 provided neurochemical, histological and functional protection against 6‐OHDA lesion of the nigrostriatal tract. Pretreatment with CPPG inhibited these effects.

Conclusions and implications:  These findings highlight group III mGlu receptors in the SN as potential targets for providing both symptomatic and neuroprotective relief in PD, and indicate that inhibition of glutamate release in the SN may underlie these effects.
Modulation of the apelin/APJ system in heart failure and atherosclerosis in man
Authors: Pitkin Sarah L , Maguire Janet J , Kuc Rhoda E , Davenport Anthony P
Published: April 2010

Background and purpose:  The aim of this study was to determine whether the apelin/APJ system is altered in human cardiovascular disease by investigating whether the expression of apelin or its receptor is altered at the protein level.

Experimental approach:  Radioligand binding studies were used to determine apelin receptor density in human cardiac tissues. Apelin peptide levels in cardiovascular tissues were determined by radioimmunoassay. In vitro pharmacology was used to assess vasoactive properties of apelin in human coronary artery. Localization of apelin and its receptor in coronary artery was determined using immunohistochemistry.

Key results:  Apelin receptor density was significantly decreased in left ventricle from patients with dilated cardiomyopathy or ischaemic heart disease compared with controls, but apelin peptide levels remained unchanged. Apelin was up‐regulated in human atherosclerotic coronary artery and this additional peptide localized to the plaque, colocalizing with markers for macrophages and smooth muscle cells. Apelin potently constricted human coronary artery.

Conclusions and implications:  We have detected changes in the apelin/APJ system in human diseased cardiac and vascular tissue. The decrease in receptor density in heart failure may limit the positive inotropic actions of apelin, contributing to contractile dysfunction. The contribution of the increased apelin levels in atherosclerotic coronary artery to disease progression remains to be determined. These data suggest a potential role for the apelin/APJ system in human cardiovascular disease.
Identification of sites responsible for the potentiating effect of niflumic acid on ClC‐Ka kidney chloride channels
Authors: Zifarelli G , Liantonio A , Gradogna A , Picollo A , Gramegna G , De Bellis M , Murgia AR , Babini E , Conte Camerino D , Pusch M
Published: April 2010

Background and purpose: ClC‐K kidney Cl–channels are important for renal and inner ear transepithelial Cl–transport, and are potentially interesting pharmacological targets. They are modulated by niflumic acid (NFA), a non‐steroidal anti‐inflammatory drug, in a biphasic way: NFA activates ClC‐Ka at low concentrations, but blocks the channel above ∼1 mM. We attempted to identify the amino acids involved in the activation of ClC‐Ka by NFA.

Experimental approach: We used site‐directed mutagenesis and two‐electrode voltage clamp analysis of wild‐type and mutant channels expressed inXenopusoocytes. Guided by the crystal structure of a bacterial CLC homolog, we screened 97 ClC‐Ka mutations for alterations of NFA effects.

Key results: Mutations of five residues significantly reduced the potentiating effect of NFA. Two of these (G167A and F213A) drastically altered general gating properties and are unlikely to be involved in NFA binding. The three remaining mutants (L155A, G345S and A349E) severely impaired or abolished NFA potentiation.

Conclusions and implications: The three key residues identified (L155, G345, A349) are localized in two different protein regions that, based on the crystal structure of bacterial CLC homologs, are expected to be exposed to the extracellular side of the channel, relatively close to each other, and are thus good candidates for being part of the potentiating NFA binding site. Alternatively, the protein region identified mediates conformational changes following NFA binding. Our results are an important step towards the development of ClC‐Ka activators for treating Bartter syndrome types III and IV with residual channel activity.
The Nightly Round: Space, Social Capital, and Urban Black Nightlife
Authors: Hunter Marcus Anthony
Published: April 2010

Using data generated from participant observation and semistructured interviews, I consider the ways in which nightlife, or what might be imagined as the nightly round—a process encompassing the social interactions, behaviors, and actions involved in going to, being in, and leaving the club—is used to mitigate the effects of social and spatial isolation, complementing the accomplishment of the daily round. Through an analysis of the social world of the Spot, I argue that understanding the ways in which urban blacks use space in the nightclub to mediate racial segregation, sexual segregation, and limited social capital expands our current understanding of the spatial mobility of urban blacks as well as the important role of extra–neighborhood spaces in such processes. Further, I highlight the ways that urban blacks use space in the nightclub to leverage socioeconomic opportunities and enhance social networks. While I found that black heterosexual and lesbian and gay patrons used space in similar ways at the Spot, black lesbians and gays were more likely to use the club as a space to develop ties of social support.
City Tour Guides: Urban Alchemists at Work
Authors: Wynn Jonathan R.
Published: April 2010

Urban sociology, often and quite reasonably, emphasizes the effects of large–scale and corporate cultures of cities and yet, at the smaller scale, there is a diverse and complex set of practices that reinvigorate the urban landscape. By pairing ethnographic fieldnotes with interviews, this paper offers a limited rejoinder to these narratives, evincing the lived interactions of one set of characters that reenchants cities. for the purposes of this article, walking tour guides serve as examples of “urban alchemists,” and three of their practices are advanced for discussion: their use of myths and revelatory stories to uproot banal visions of the city; their aim to incorporate chance and serendipity into their interactions; and their attempts to transform their participants into “better” urban dwellers.
Foregrounding Nature: An Invitation to think about Shifting Nature–City Boundaries
Authors: Čapek Stella M.
Published: April 2010

Although nature in the form of “environment” has sometimes been part of sociological discussions of the city, it is typically treated as background, as a social construction, or as a metaphor for social processes. Less familiar is a view of nature as an active participant in a relationship of codetermination, an “actor” that constructs outcomes along with human beings in the communities that they inhabit. in this essay, I explore this more agentic reading of nature, bringing together insights from environmental and urban/community sociology. I explore four areas in which taken–for–granted boundaries between nature and city are shifting: ecological restoration projects, human–animal interactions, “postnatural” environments of toxic pollution, and simulated/artificial environments that substitute for nature. I suggest that urban sociology would benefit from a socioecological approach that enriches our understanding of nature and city and that allows us to participate more fully in discussions of sustainability.
Evaluation of a multifaceted intervention to limit excessive antipsychotic co‐prescribing in schizophrenia out‐patients
Authors: Baandrup L. , Allerup P. , Lublin H. , Nordentoft M. , Peacock L. , Glenthoj B.
Published: April 2010

Baandrup L, Allerup P, Lublin H, Nordentoft M, Peacock L, Glenthoj B. Evaluation of a multifaceted intervention to limit excessive antipsychotic co‐prescribing in schizophrenia out‐patients.

Objective: To evaluate the effect of a multifaceted educational intervention on the frequency of antipsychotic co‐prescribing in adult schizophrenia out‐patients.

Method: Controlled quasi‐experimental study performed in two Danish municipalities matched for baseline prevalence of antipsychotic polypharmacy, socioeconomic status and functional level of patients. The intervention was aimed at psychiatric healthcare providers and consisted of 1 day of didactic lectures, six 3‐h educational outreach visits and an electronic reminder during drug prescribing.

Results: Between‐group use of antipsychotic polypharmacy was compared at baseline (intervention group,N = 232/control group,N = 351) and after 1 year of intervention (intervention group,N = 216/control group,N = 386). The prevalence of antipsychotic polypharmacy at follow‐up was not significantly different between treatment settings when adjusting for differences in case‐mix (P = 0.07).

Conclusion: This multifaceted educational intervention failed to reduce the frequency of antipsychotic co‐prescribing, but it suggested that future efforts to improve prescribing practice should address organizational barriers to implementation.
Parameters for Successful Implant Integration Revisited Part II: Algorithm for Immediate Loading Diagnostic Factors
Authors: Bahat Oded , Sullivan Richard M.
Published: April 2010

Immediate loading of dental implants has become a widely reported practice with success rates ranging from 70.8% to 100%. Although most studies have considered implant survival to be the only measure of success, a better definition includes the long‐term stability of the hard and soft tissues around the implant(s) and other adjacent structures, as well as the long‐term stability of all the restorative components. The parameters identified in 1981 by Albrektsson and colleagues as influencing the establishment and maintenance of osseointegration have been reconsidered in relation to immediate loading to improve the chances of achieving such success. Two of the six parameters (status of the bone/implant site and implant loading conditions) have preoperative diagnostic implications, whereas three (implant design, surgical technique, and implant finish) may compensate for less‐than‐ideal site and loading conditions. Factors affecting the outcome of immediate loading are reviewed to assist clinicians attempting to assess its risks and benefits.
Arg143 and Lys192 of the human mast cell chymase mediate the preference for acidic amino acids in position P2′ of substrates
Authors: Andersson Mattias K. , Thorpe Michael , Hellman Lars
Published: April 2010

Chymases are chymotrypsin‐like serine proteases that are found in large amounts in mast cell granules. So far, the extended cleavage specificities of eight such chymases have been determined, and four of these were shown to have a strong preference for acidic amino acids at position P2′. These enzymes have basic amino acids in positions 143 and 192 (Arg and Lys, respectively). We therefore hypothesized that Arg143 and Lys192 of human chymase mediate the preference for acidic amino acids at position P2′ of substrates. In order to address this question, we performed site‐directed mutagenesis of these two positions in human chymase. Analysis of the extended cleavage specificities of two single mutants (Arg143 → Gln and Lys192 → Met) and the combined double mutant revealed an altered specificity for P2′ amino acids, whereas all other positions were essentially unaffected. A weakened preference for acidic amino acids at position P2′ was observed for the two single mutants, whereas the double mutant lacked this preference. Therefore, we conclude that positions 143 and 192 in human chymase contribute to the strong preference for negatively charged amino acids at position P2′. This is the first time that a similar combined effect has been shown to influence the cleavage specificity, apart from position P1, among the chymases. Furthermore, the conservation of the preference for acidic P2′ amino acids for several mast cell chymases clearly indicates that other substrates than angiotensin I may be major in vivo targets for these enzymes.
Selection of full‐length IgGs by tandem display on filamentous phage particles and Escherichia coli fluorescence‐activated cell sorting screening
Authors: Mazor Yariv , Van Blarcom Thomas , Carroll Sean , Georgiou George
Published: April 2010

Phage display of antibody libraries is a powerful tool for antibody discovery and evolution. Recombinant antibodies have been displayed on phage particles as scFvs or Fabs, and more recently as bivalent F(ab′)2. We recently developed a technology (E‐clonal) for screening of combinatorial IgG libraries using bacterial periplasmic display and selection by fluorescence‐activated cell sorting (FACS) [Mazor Y et al. (2007) Nat Biotechnol25, 563–565]. Although, as a single‐cell analysis technique, FACS is very powerful, especially for the isolation of high‐affinity binders, even with state of the art instrumentation the screening of libraries with diversity > 108 is technically challenging. We report here a system that takes advantage of display of full‐length IgGs on filamentous phage particles as a prescreening step to reduce library size and enable subsequent rounds of FACS screening in Escherichia coli. For the establishment of an IgG phage display system, we utilized phagemid‐encoded IgG with the fUSE5–ZZ phage as a helper phage. These phage particles display the Fc‐binding ZZ protein on all copies of the phage p3 coat protein, and are exploited as both helper phages and anchoring surfaces for the soluble IgG. We demonstrate that tandem phage selection followed by FACS allows the selection of a highly diversified profile of binders from antibody libraries without undersampling, and at the same time capitalizes on the advantages of FACS for real‐time monitoring and optimization of the screening process.
Modulation of the Arabidopsis KAT1 channel by an activator of protein kinase C in Xenopus laevis oocytes
Authors: Sato Aiko , Gambale Franco , Dreyer Ingo , Uozumi Nobuyuki
Published: April 2010

The Arabidopsis thaliana K+ channel KAT1 has been suggested to play a key role in the regulation of the aperture of stomatal pores on the surface of plant leaves. Calcium‐dependent and calcium‐independent signaling pathways are involved in abscisic acid‐mediated regulation of guard cell turgidity. Although the activity of the KAT1 channel is thought to be regulated by calcium‐dependent protein kinases, the effect of phosphorylation on KAT1 and the phosphorylated target sites remain elusive. Because it has been proposed that the phosphorylation recognition sequence of plant calcium‐dependent protein kinases resembles that of animal protein kinases C, in this study, we used the Xenopus laevis oocyte protein kinase C to identify the target sites of calcium‐dependent protein kinases. KAT1 expressed in Xenopus oocytes was inhibited by the protein kinase C activator phorbol 12‐myristate 13‐acetate. On the basis of an in silico search, we selected S/T‐X‐K/R motifs facing the cytosol, as it has been reported that protein kinase C and calcium‐dependent protein kinase share a common consensus sequence. Mutagenesis analyses revealed that six Ser/Thr residues were responsible for the reduction in activity after phorbol 12‐myristate 13‐acetate application. Simultaneous mutation of the five residues located in the carboxyl‐terminus region of KAT1 led to a K+ channel mutant that was insensitive to protein kinase C. These results indicate that, in plant cells, a kinase analogous to protein kinase C might exist that may modulate KAT1 channel activity through calcium‐dependent phosphorylation at some of the pinpointed residues in the cytosolic region of KAT1.
Novel cathelicidin‐derived antimicrobial peptides from Equus asinus
Authors: Lu Zekuan , Wang Yipeng , Zhai Lei , Che Qiaolin , Wang Hui , Du Shuyuan , Wang Duo , Feng Feifei , Liu Jingze , Lai Ren , Yu Haining
Published: April 2010

In the present study, EA‐CATH1 and EA‐CATH2 were identified from a constructed lung cDNA library of donkey (Equus asinus) as members of cathelicidin‐derived antimicrobial peptides, using a nested PCR‐based cloning strategy. Composed of 25 and 26 residues, respectively, EA‐CATH1 and EA‐CATH2 are smaller than most other cathelicidins and have no sequence homology to other cathelicidins identified to date. Chemically synthesized EA‐CATH1 exerted potent antimicrobial activity against most of the 32 strains of bacteria and fungi tested, especially the clinically isolated drug‐resistant strains, and minimal inhibitory concentration values against Gram‐positive bacteria were mostly in the range of 0.3–2.4 μg·mL−1. EA‐CATH1 showed an extraordinary serum stability and no haemolytic activity against human erythrocytes in a dose up to 20 μg·mL−1. CD spectra showed that EA‐CATH1 mainly adopts an α‐helical conformation in a 50% trifluoroethanol/water solution, but a random coil in aqueous solution. Scanning electron microscope observations of Staphylococcus aureus (ATCC2592) treated with EA‐CATH1 demonstrated that EA‐CATH could cause rapid disruption of the bacterial membrane, and in turn lead to cell lysis. This might explain the much faster killing kinetics of EA‐CATH1 than conventional antibiotics revealed by killing kinetics data. In the presence of CaCl2, EA‐CATH1 exerted haemagglutination activity, which might potentiate an inhibition against the bacterial polyprotein interaction with the host erythrocyte surface, thereby possibly restricting bacterial colonization and spread.
A DNA‐binding surface of SPO11‐1, an Arabidopsis SPO11 orthologue required for normal meiosis
Authors: Shingu Yoshinori , Mikawa Tsutomu , Onuma Mariko , Hirayama Takashi , Shibata Takehiko
Published: April 2010

Meiotic recombination is initiated by DNA double‐stranded breaks introduced by the SPO11 protein. Despite a decade of research, the biochemical functions of SPO11 remain largely unknown, perhaps because of difficulties in studying the functionally active SPO11. Arabidopsis thaliana encodes three SPO11‐related proteins, two of which (SPO11‐1 and SPO11‐2) are required for, and cooperate in, meiosis. We isolated soluble SPO11‐1, fused with or free of a trigger factor‐tag at its N terminus. The tag‐free SPO11‐1 needed to interact physically with soluble SPO11‐1 to maintain its solubility, suggesting a multimeric active form including a solubilizing protein cofactor. An N‐terminal fragment of PRD1, a SPO11‐1‐interacting protein required for normal meiosis, but not SPO11‐2, forms a soluble complex with trigger factor‐tagged SPO11‐1, but the trigger factor‐tag was required for the solubility. Formation of the complex is not sufficient to express endonuclease activity. Trigger factor‐tagged SPO11‐1 exhibited DNA‐binding activities: Glu substitutions of the invariant Gly215 and Arg222 and of the nonconserved Arg223 and Arg226 in a conserved motif (G215E, R222E, R223E, R226E) reduced the DNA‐binding ability in vitro, but substitutions of the conserved Arg130 and invariant Tyr103 (a residue in the putative endonuclease‐active center) and of Arg residues outside conserved motifs by Glu or Phe (R130E, Y103F, R207E and R254E), did not. Tests for the ability of mutant spo11‐1 proteins to complement the silique‐defective phenotype of a spo11‐1‐homozygous mutant in vivo revealed that R222E and G215E induced serious deficiencies, while R130E caused a partial defect in silique formation. Thus, the Gly215, Arg222 and Arg223 residues of SPO11‐1 form a DNA‐binding surface that is functional in meiosis.
Classification of the short‐chain dehydrogenase/reductase superfamily using hidden Markov models
Authors: Kallberg Yvonne , Oppermann Udo , Persson Bengt
Published: April 2010

The short‐chain dehydrogenase/reductase (SDR) superfamily now has over 47 000 members, most of which are distantly related, with typically 20–30% residue identity in pairwise comparisons, making it difficult to obtain an overview of this superfamily. We have therefore developed a family classification system, based upon hidden Markov models (HMMs). To this end, we have identified 314 SDR families, encompassing about 31 900 members. In addition, about 9700 SDR forms belong to families with too few members at present to establish valid HMMs. In the human genome, we find 47 SDR families, corresponding to 82 genes. Thirteen families are present in all three domains (Eukaryota, Bacteria, and Archaea), and are hence expected to catalyze fundamental metabolic processes. The majority of these enzymes are of the ‘extended’ type, in agreement with earlier findings. About half of the SDR families are only found among bacteria, where the ‘classical’ SDR type is most prominent. The HMM‐based classification is used as a basis for a sustainable and expandable nomenclature system.