bluuebunny/crossref_metadata_2025 huggingface dataset:
Workplace aggression: the effects of harassment on job burnout and turnover intentions
Authors: Deery Stephen , Walsh Janet , Guest David
Published: December 2011

This article analyses the impact of harassment on job burnout and turnover intentions among a large sample of hospital nurses in Britain. It compares the effects of insider-initiated harassment from managers and colleagues with outsider-initiated harassment from patients and their relatives. The article also examines the effect of ethnicity and the impact of effective anti-harassment policies on job burnout and quit intentions. Results suggest firstly, that the insider or outsider characteristics of the perpetrator do help to shape the consequences of harassment for nurses and secondly, that effective anti-harassment policies do reduce turnover intentions, particularly for minority ethnic nurses.
Theorizing financialization
Authors: Lapavitsas Costas
Published: December 2011

The crisis of 2007–9 has cast fresh light on the ascendancy of finance in recent years, a process that is often described as financialization. The concept of financialisation has emerged within Marxist political economy in an effort to relate booming finance to poorly performing production. Yet, there is no general agreement on what it means, as is shown in this article through a selective review of economic and sociological literature. The article puts forth an analysis of financialization that draws on classical Marxism while remaining mindful of the recent crisis. Financialization represents a systemic transformation of mature capitalist economies with three interrelated features. First, large corporations rely less on banks and have acquired financial capacities; second, banks have shifted their activities toward mediating in open financial markets and transacting with households; third, households have become increasingly involved in the operations of finance. The sources of capitalist profit have also changed accordingly.
Reconstruction amid deconstruction: or why we need more of the social in European social models
Authors: Rubery Jill
Published: December 2011

This article makes two key arguments. First, European social models are being asked to extend social support to meet new needs associated with the ageing society, changes in citizens’ aspirations and behaviour and the reduced reliability of support from employers and the family. How nations respond to these new needs varies according to current gaps in provision and to political will, but most states up to the crisis were expanding their range of social interventions, sometimes leading to hybridization of their traditional social models. Second, deconstruction of social models to implement neoliberalism and reconstruction to meet new needs are often two sides of the same process. Reforms to meet new needs may take a neoliberal form, and neoliberal reforms may generate new needs. European social models may have to respond to these pressures for, unlike those of the USA, European citizens still look to the state to ensure their social citizenship rights.
Measuring discrimination facing ethnic minority job applicants: an Irish experiment
Authors: McGinnity Frances , Lunn Peter D.
Published: December 2011

The role of employer discrimination in labour market matching is often acknowledged but challenging to quantify. What part of the ‘ethnic penalty’ in the labour market is due to recruitment discrimination? This experiment, the first of its kind in Ireland, explicitly measured this by sending out nearly 500 equivalent CVs from Irish and minority candidates in response to advertised vacancies in the greater Dublin area. We find that candidates with Irish names are over twice as likely to be called to interview as are candidates with an African, Asian or German name. This discrimination rate is high by international standards, and does not vary between minority groups. We develop the discussion of the role of prejudice and stereotypes in discrimination in this article, arguing that our findings may be linked to the fact that Ireland is a ‘new immigration’ country, with no established minority groups and a cohesive national identity.
Flexicurity, employment protection and the jobs crisis
Authors: Heyes Jason
Published: December 2011

The concept of ‘flexicurity’ has become ubiquitous in the labour market policy recommendations of the European Commission. EU member states have been encouraged to increase labour market flexibility while maintaining security through the promotion of ‘employability’ and an ‘adequate’ floor of unemployment benefits. The economic crisis that erupted in 2008 has, however, provided flexicurity measures with a strenuous test. As this article demonstrates, those countries that have maintained relatively strong employment protections have tended to experience fewer labour market disruptions than countries with weaker employment protections. The article also suggests that while there has been some convergence in employment and social protection policy across Europe, the trend has been towards less security rather than ‘flexicurity’.
Aesthetic and emotional labour through stigma: national identity management and racial abuse in offshored Indian call centres
Authors: Nath Vandana
Published: December 2011

This article examines the emotional complexities and stresses associated with national identity management (accent modification, the use of western pseudonyms and location masking) and customer-instigated racial abuse in offshored Indian call centres. Drawing on 77 semi-structured interviews with frontline employees in Bangalore, the research reveals that although call centre agents can find identity management beneficial in easing customer apprehensions and in achieving organizational performance targets, such identity regulation can result in the experience of stress, role ambiguity and work alienation. The article demonstrates that employees need to manage the stigma relating to their ‘Indian’ identity in order to fulfil the challenges of aesthetic and emotional labour. Furthermore, the article explains how the mobilization of aesthetic labour through stigma management can intensify frontline worker experiences of emotional labour.
The impact of the economic crisis on international migration: a review
Authors: Tilly Chris
Published: December 2011

The global economic crisis that exploded in 2008 dramatically changed the context for international migration. In that context, this review article addresses four related questions about migration from poor to rich countries. First, what has been the impact of the global recession on patterns of international migration? Second, to what extent do recession-induced changes in migration offer evidence in the debate among competing explanations of migration? Third, has the recession heightened the marginalization of migrants? Fourth, to what extent have nations responded to the recession by regulating migration in new ways? Findings include reduced migration flows in the recession, evidence for both economic and social explanations, little evidence in unemployment rates for further marginalization of migrants and limited movement toward added migration restrictions.
Cortical Shape Adaptation Transforms a Circle Into a Hexagon
Authors: Ito Hiroyuki
Published: December 2011

After viewing a colored figure on a uniform gray background, an observer will see a negative afterimage after the colored figure disappears. This study shows that the shapes of afterimages vary systematically according to the shape of the adaptation stimuli, a phenomenon that could be caused only by cortical shape adaptation. In the experiments reported here, participants typically saw a hexagonal afterimage after viewing a circle and sometimes saw a circular afterimage after viewing a hexagon. When observers were adapted to rotating circles or hexagons, which produced the same circular retinal painting, they reliably reported that afterimages of circles appeared as hexagons, and vice versa. Furthermore, the fact that this effect also arose through interocular transfer confirms that a cortical process with binocular inputs must have contributed to it. This novel finding reveals that afterimage formation is determined mainly by a cortical process, not by retinal bleaching, and that rival mechanisms detect corners and curves of shapes in cortical processing.
Tree ring-based annual streamflow reconstruction for the Heihe River in arid northwestern China from ad 575 and its implications for water resource management
Authors: Yang Bao , Qin Chun , Shi Feng , Sonechkin Dmitry M.
Published: December 2011

We developed two tree ring-width chronologies (Qilian juniper, Sabina przewalskii Kom.) for the inland Heihe River Basin in arid northwest China using a large number of tree-ring samples (217 samples/92 trees) with accurate information about pith offsets based on Regional Curve Standardization (RCS) and standard dendrochronological (STD) methodologies. Two 1422-year reconstructions of annual (August–July) streamflow for the upstream region of the Heihe River are presented. The STD and RCS reconstructions account for 53.4% and 57.2% of the actual streamflow variance during the period 1958–2006, respectively. Both reconstructions display considerable low frequency (multidecadal to multicentury) fluctuations, although the RCS based reconstruction is superior to the STD based reconstruction for retention of low-frequency trends. Low-flow years in ad 818–852, 1112–1196, 1453–1495 and 1680–1710, and high-flow periods in ad 868–1000, 1056–1094, 1228–1271, 1327–1440, 1510–1583 and 1877–2006 are detected in both reconstructions. Both the STD and the RCS reconstructions testify to the fact that the 20th century witnessed intensified pluvial conditions in the upstream region of the Heihe River in the context of the last 1500 years. The streamflow reconstructions are anticipated to be useful to water resource planning and management for the Heihe River Basin in arid northwestern China.
Seasonal temperature variability during the past 1600 years recorded in historical documents and varved lake sediment profiles from northeastern China
Authors: Chu Guoqiang , Sun Qing , Wang Xiaohua , Liu Meimei , Lin Yuan , Xie Manman , Shang Wenyu , Liu Jiaqi
Published: December 2011

Seasonal temperature variability over longer timescales could offer new insights into understanding different forcing factors and response processes in the climate system. Here we report an alkenone-based temperature reconstruction for growing season over the past 1600 years from the varved sediment in Lake Sihailongwan, northeastern China. The most notable cold spells occurred during the periods ad 480–860, ad 1260–1300, ad 1510–1570 and ad 1800–1900 with a temperature decrease of about 1°C compared with the 20th century. Based on the historical evidence such as ‘snow or frost in the summertime’ and ‘no ice during the wintertime’, we compile extreme cold summer events and warm winter events over the past 1600 years. The ‘Little Ice Age’ time period experienced more extreme cold summer/warm winter events, while the ‘Medieval Warm Period’ had milder winters. Comparatively, the natural proxy data show a general similar pattern with historical documents at decadal time scales, except for between ad 1620 and 1720. Our results show multidecadal to centennial variations in seasonal temperature, possibly caused by interactions of external natural forcing and atmosphere–ocean circulations.
Seeing-Ourselves-in-the-World
Authors: Killick David
Published: December 2011

Taking a model of global citizenship that is primarily a matter of seeing the self-in-the-world as one dwelling among others, this article focuses on experiences of students with individual “significant others” and among international student communities, drawing on a 3-year study into U.K. undergraduate students participating in international mobility activities. Participants reveal how lived experience of Otherness in such intersubjective encounters enables moves to identify Self with others and to personalize hitherto distant places and practices. Even in the context of international mobility, encountering difference does not depend on the crossing of national cultures but on recognizing Otherness in all we may engage with and in ourselves. Most of the encounters in this study take place outside of the host culture or the “designed” features of the international mobility activities, suggesting opportunities for multicultural/international campuses to develop spaces for similarly rich learning for the nonmobile majority.
Burnout and Connectedness in the Job Demands–Resources Model
Authors: Huynh Jasmine-Yan , Winefield Anthony H. , Xanthopoulou Despoina , Metzer Jacques C.
Published: December 2011

This study examined the role of burnout and connectedness in the job demands–resources (JD-R) model among palliative care volunteers. It was hypothesized that ( a) exhaustion mediates the relationship between demands and depression, and between demands and retention; ( b) cynicism mediates the relationship between resources and retention; and ( c) connectedness mediates the relationship between resources and retention. Hypotheses were tested in 2 separate analyses: structural equation modeling (SEM) and path analyses. The first was based on volunteer self-reports (N = 204), while the second analysis concerned matched data from volunteers and their family members (N = 99). While strong support was found for cynicism and connectedness as mediators in both types of analyses, this was not altogether the case for exhaustion. Implications of these findings for the JD-R model and volunteer organizations are discussed.
Visual Form, Ethics, and a Typology of Purpose
Authors: Rosenquist Christina
Published: December 2011

Stallworth Williams introduces concepts of visual rhetoric and ethics for a classroom exercise in the analysis and revision of a sales letter. This article revisits Stallworth Williams’s proposed teaching strategies, suggesting that not only do students need to be instructed in elements of visual design, but they must also be taught to link those elements to specific decorative, indicative, or informative purposes. This method teaches students to design documents that meet shared goals (designer and recipient) and to recognize where designs fail in purpose, so revisions can be made using deliberate choice, based on a systematic framework.
Creating the Tourist Product in the Opposition Between Self-Actualization and Collective Consumption
Authors: Lauring Jakob
Published: December 2011

Being a popular way of traveling, charter tourism has received an often derogatory image. This may be related to dominating societal ideals promoting self-actualization and individual exploration. However, not much is known about the development of motivations and behaviors among charter tourists. By use of ethnographic fieldwork methodology, this exploratory study investigated a group of Danish charter tourists traveling to Gran Canaria. Results show that the charter tourists were active in navigating between central dichotomies posed by the consumption of a mass product in an individualized societal context, thereby shaping their experiences to form a desirable tourist product. Implications of these findings are discussed in detail.
Has Europe got anything to do with the European elections? A study on split-ticket voting in the Belgian regional and European elections of 2009
Authors: Van Aelst Peter , Lefevere Jonas
Published: December 2011

This study explains why people voted differently in the 2009 regional and European elections in Belgium. By comparing loyal voters and voters who split their ticket, the article shows that a part of the electorate is driven by Euro-specific motivations. The proportion of people who truly vote ‘European’ depends on the political context, and more precisely on what parties offer the voters in terms of candidates and issues. However, the European dimension is not the only mechanism that underlies voters’ electoral choices at the European level. In particular, uncertain voters, who lack a clear preference for one party at the national level, are likely to split their ticket between the regional and European elections.
Playing with/through non-fiction texts: Young children authoring their relationships with history
Authors: Ghiso María Paula
Published: December 2011

This article examines the relationship between literacy and play in six- and seven-year-olds’ engagement with non-fiction writing. I draw from a year-long ethnographic study (Erickson, 1986) of a US classroom's ‘writing time’, intentionally structured on children’s own interests and enquiries. Rather than strict adherence to monolithic models described in the school region’s mandated curriculum and assessments, the children treated genres as porous and used writing as a tool for multi-modal play. In authoring and interacting with non-fiction texts, they blended ‘real’ and ‘imaginary’ worlds as they communed with historical figures on their own terms. Children used play to enquire into and manipulate the parameters of non-fiction, authoring their relationships with knowledge in the process. Through their exchanges with one another, children became familiar with non-fiction topics. At the same time, their play positioned conventional academic discourses as being open to transformation. This article makes an argument for a more synergistic conception of ‘serious’ and ‘playful’ authoring practices, and for the role of play as a component of critical literacy.
Writing and resistance
Authors: Clughen Lisa , Connell Matt
Published: December 2011

Support for writing instruction amongst lecturers in UK Universities is high, but they often prefer it to be provided by dedicated study skills specialists operating outside subject curricula. Yet because of the well-documented problems with the skills approach (where literacy support frequently becomes a generic add-on), American models such as Writing Across the Curriculum (WAC) and Writing in the Disciplines (WID) make a strong claim that writing stratagems and thinking/theorizing within disciplines are actually intrinsically linked. It is accordingly now a commonplace in such literacy research that writing development needs to be contextualized within the disciplines, and interest in adapting such approaches to the UK context is burgeoning. A recent project at Nottingham Trent University set out to explore the prospects for such an adaption through the piloting of an embedded approach in the Social Theory subject area, but the project ran into a series of resistances that came close to thwarting it entirely. The initial challenge lay in convincing time-poor subject lecturers to engage with the literacy initiative and to find space for it in an already saturated curriculum. Yet it seemed that behind the surface perception that the embedding of literacy development would be onerous, or would squeeze out core subject content, there lay a deeper attitude that such development was both ‘beneath’ subject lecturers and unconnected to the specific concerns of their academic discipline. This reflection piece, co-written by the academic support coordinator championing the initiative and the Social Theory Subject Leader, seeks to understand some of these attitudes, using the work of Sigmund Freud and Theodor W. Adorno to probe various psycho-social aspects of the phenomenon of resistance to the embedding of writing development in a discipline. What emerges is a reflection on practice which arguably reveals a certain complex around the status of teaching as opposed to lecturing, alongside a process of displaced resistance to the managerialist and vocationalizing discourse which is on the ascendency within UK universities.
Elimination of Position-Change Alarms in an Alzheimer’s and Dementia Long-Term Care Facility
Authors: Bressler Katrina , E.Redfern Roberta , Brown Megan
Published: December 2011

In a long-term care facility, whose residents have been diagnosed with Alzheimer’s disease or dementia, falls are a particularly prominent issue. Technology in health care has continued to evolve and play a larger role in how we care for our patients, even in preventing falls. However, overreliance on these types of technologies may have detrimental effects. In our facility, it was felt that staff reliance on position-change alarms was inappropriate due to the high rate of false alarms associated with these devices. We took a tiered approach to removing position-change alarms from our facility, monitoring the fall incidence rate for a period before, during, and after the elimination of these alarms. After discontinuing their use, we found a decrease in the rate of falls, and a decrease in the percentage of our residents who fell. Staff has easily adapted and reports a calmer, more pleasant environment.
Genome-wide analysis of histone H3 acetylation patterns in AML identifies PRDX2 as an epigenetically silenced tumor suppressor gene
Authors: Agrawal-Singh Shuchi , Isken Fabienne , Agelopoulos Konstantin , Klein Hans-Ulrich , Thoennissen Nils H. , Koehler Gabriele , Hascher Antje , Bäumer Nicole , Berdel Wolfgang E. , Thiede Christian , Ehninger Gerhard , Becker Anke , Schlenke Peter , Wang Yipeng , McClelland Michael , Krug Utz , Koschmieder Steffen , Büchner Thomas , Yu Dae-Yeul , Singh Shailendra Vikram , Hansen Klaus , Serve Hubert , Dugas Martin , Müller-Tidow Carsten
Published: December 2011

With the use of ChIP on microarray assays in primary leukemia samples, we report that acute myeloid leukemia (AML) blasts exhibit significant alterations in histone H3 acetylation (H3Ac) levels at > 1000 genomic loci compared with CD34+ progenitor cells. Importantly, core promoter regions tended to have lower H3Ac levels in AML compared with progenitor cells, which suggested that a large number of genes are epigenetically silenced in AML. Intriguingly, we identified peroxiredoxin 2 (PRDX2) as a novel potential tumor suppressor gene in AML. H3Ac was decreased at the PRDX2 gene promoter in AML, which correlated with low mRNA and protein expression. We also observed DNA hypermethylation at the PRDX2 promoter in AML. Low protein expression of the antioxidant PRDX2 gene was clinically associated with poor prognosis in patients with AML. Functionally, PRDX2 acted as inhibitor of myeloid cell growth by reducing levels of reactive oxygen species (ROS) generated in response to cytokines. Forced PRDX2 expression inhibited c-Myc–induced leukemogenesis in vivo on BM transplantation in mice. Taken together, epigenome-wide analyses of H3Ac in AML led to the identification of PRDX2 as an epigenetically silenced growth suppressor, suggesting a possible role of ROS in the malignant phenotype in AML.
The disulfide isomerase ERp57 mediates platelet aggregation, hemostasis, and thrombosis
Authors: Wu Yi , Ahmad Syed S. , Zhou Junsong , Wang Lu , Cully Matthew P. , Essex David W.
Published: December 2011

A close homologue to protein disulfide isomerase (PDI) called ERp57 forms disulfide bonds in glycoproteins in the endoplasmic reticulum and is expressed on the platelet surface. We generated 2 rabbit Abs to ERp57. One Ab strongly inhibited ERp57 in a functional assay and strongly inhibited platelet aggregation. There was minimal cross-reactivity of this Ab with PDI by Western blot or in the functional assay. This Ab substantially inhibited activation of the αIIbβ3 fibrinogen receptor and P-selectin expression. Furthermore, adding ERp57 to platelets potentiated aggregation. In contrast, adding a catalytically inactive ERp57 inhibited platelet aggregation. When infused into mice the inactive ERp57 prolonged the tail bleeding times. We generated 2 IgG2a mAbs that reacted with ERp57 by immunoblot. One of these Abs inhibited both ERp57 activity and platelet aggregation. The other Ab did not inhibit ERp57 activity or platelet aggregation. The inhibitory Ab inhibited activation of αIIbβ3 and P-selectin expression, prolonged tail bleeding times, and inhibited FeCl3-induced thrombosis in mice. Finally, we found that a commonly used mAb to PDI also inhibited ERp57 activity. We conclude that a glycoprotein-specific member of the PDI family, ERp57, is required for platelet aggregation, hemostasis, and thrombosis.
miR-27b controls venous specification and tip cell fate
Authors: Biyashev Dauren , Veliceasa Dorina , Topczewski Jacek , Topczewska Jolanta M. , Mizgirev Igor , Vinokour Elena , Reddi Alagarsamy L. , Licht Jonathan D. , Revskoy Sergei Y. , Volpert Olga V.
Published: December 2011

We discovered that miR-27b controls 2 critical vascular functions: it turns the angiogenic switch on by promoting endothelial tip cell fate and sprouting and it promotes venous differentiation. We have identified its targets, a Notch ligand Delta-like ligand 4 (Dll4) and Sprouty homologue 2 (Spry2). miR-27b knockdown in zebrafish and mouse tissues severely impaired vessel sprouting and filopodia formation. Moreover, miR-27b was necessary for the formation of the first embryonic vein in fish and controlled the expression of arterial and venous markers in human endothelium, including Ephrin B2 (EphB2), EphB4, FMS-related tyrosine kinase 1 (Flt1), and Flt4. In zebrafish, Dll4 inhibition caused increased sprouting and longer intersegmental vessels and exacerbated tip cell migration. Blocking Spry2 caused premature vessel branching. In contrast, Spry2 overexpression eliminated the tip cell branching in the intersegmental vessels. Blockade of Dll4 and Spry2 disrupted arterial specification and augmented the expression of venous markers. Blocking either Spry2 or Dll4 rescued the miR-27b knockdown phenotype in zebrafish and in mouse vascular explants, pointing to essential roles of these targets downstream of miR-27b. Our study identifies critical role of miR-27b in the control of endothelial tip cell fate, branching, and venous specification and determines Spry2 and Dll4 as its essential targets.
Prognostic value of monosomal karyotype in comparison to complex aberrant karyotype in acute myeloid leukemia: a study on 824 cases with aberrant karyotype
Authors: Haferlach Claudia , Alpermann Tamara , Schnittger Susanne , Kern Wolfgang , Chromik Jörg , Schmid Christoph , Pielken Hermann Josef , Kreuzer Karl-Anton , Höffkes Heinz-Gert , Haferlach Torsten
Published: December 2011

In acute myeloid leukemia (AML) the subset with complex karyotype (CK) is traditionally regarded as the worst prognostic group. However, ≥ 3, ≥ 4, or ≥ 5 abnormalities have been variably used for its definition. Recently, monosomal karyotype (MSK) was suggested to indicate an even inferior outcome. We tested which definition fits best to identify the most unfavorable subgroup. After excluding patients with t(15;17)/PML-RARA, t(8;21)/RUNX1-RUNX1T1, inv (16)/t(16;16)/CBFB-MYH11, and normal karyotype, 824 patients with AML with cytogenetic abnormalities were analyzed. Patients with MSK or CK defined as ≥ 3, ≥ 4, or ≥ 5 abnormalities showed an inferior overall survival compared with the respective remaining patients not fulfilling these criteria (for all, P < .001). Hazard ratios were 1.93, 1.68, 1.94, and 1.92. CK ≥ 4 as a single parameter identified the largest proportion of patients with very poor risk. However, combining CK ≥ 4 and MSK detected an even larger number of patients with very unfavorable outcome (261 of 824; 31.7%).
Thermodynamic and structural description of allosterically regulated VEGFR-2 dimerization
Authors: Brozzo Maurice S. , Bjelić Saša , Kisko Kaisa , Schleier Thomas , Leppänen Veli-Matti , Alitalo Kari , Winkler Fritz K. , Ballmer-Hofer Kurt
Published: December 2011

VEGFs activate 3 receptor tyrosine kinases, VEGFR-1, VEGFR-2, and VEGFR-3, promoting angiogenic and lymphangiogenic signaling. The extracellular receptor domain (ECD) consists of 7 Ig-homology domains; domains 2 and 3 (D23) represent the ligand-binding domain, whereas the function of D4-7 is unclear. Ligand binding promotes receptor dimerization and instigates transmembrane signaling and receptor kinase activation. In the present study, isothermal titration calorimetry showed that the Gibbs free energy of VEGF-A, VEGF-C, or VEGF-E binding to D23 or the full-length ECD of VEGFR-2 is dominated by favorable entropic contribution with enthalpic penalty. The free energy of VEGF binding to the ECD is 1.0-1.7 kcal/mol less favorable than for binding to D23. A model of the VEGF-E/VEGFR-2 ECD complex derived from small-angle scattering data provided evidence for homotypic interactions in D4-7. We also solved the crystal structures of complexes between VEGF-A or VEGF-E with D23, which revealed comparable binding surfaces and similar interactions between the ligands and the receptor, but showed variation in D23 twist angles. The energetically unfavorable homotypic interactions in D4-7 may be required for re-orientation of receptor monomers, and this mechanism might prevent ligand-independent activation of VEGFR-2 to evade the deleterious consequences for blood and lymph vessel homeostasis arising from inappropriate receptor activation.
Dynamics of HBV cccDNA expression and transcription in different cell growth phase
Authors: Chong Chin-Liew , Chen Mong-Liang , Wu Yi-Chieh , Tsai Kuen-Nan , Huang Chien-Chiao , Hu Cheng-po , Jeng King-Song , Chou Yu-Chi , Chang Chungming
Published: December 2011

Background

The covalently closed-circular DNA (cccDNA) of hepatitis B virus (HBV) is associated with viral persistence in HBV-infected hepatocytes. However, the regulation of cccDNA and its transcription in the host cells at different growth stages is not well understood.

Methods

We took advantages of a stably HBV-producing cell line, 1.3ES2, and examine the dynamic changes of HBV cccDNA, viral transcripts, and viral replication intermediates in different cellular growth stages.

Results

In this study, we showed that cccDNA increased suddenly in the initial proliferation phase of cell growth, probably attributable to its nuclear replenishment by intracellular nucleocapsids. The amount of cccDNA then decreased dramatically in the cells during their exponential proliferation similar to the loss of extrachromosomal plasmid DNA during cell division, after which it accumulated gradually while the host cells grew to confluency. We found that cccDNA was reduced in dividing cells and could be removed when proliferating cells were subjected to long term of lamivudine (3TC) treatment. The amounts of viral replicative intermediates were rapidly reduced in these proliferating cells and were significantly increased after cells reaching confluency. The expression levels of viral transcripts were increased in parallel with the elevated expression of hepatic transcription factors (HNF4α, CEBPα, PPARα, etc.) during cell growth confluency. The HBV transcripts were transcribed from both integrated viral genome and cccDNA, however the transcriptional abilities of cccDNA was less efficient then that from integrated viral genome in all cell growth stages. We also noted increases in the accumulation of intracellular viral particles and the secretion of mature virions as the cells reached confluency and ceased to grow.

Conclusions

Based on the dynamics of HBV replication, we propose that HBV replication is modulated differently in the different stages of cell growth, and can be divided into three phases (initial proliferation phase, exponential proliferation phase and growth confluency phase) according to the cell growth curve. The regulation of cccDNA in different cell growth phase and its importance regarding HBV replication are discussed.
MotifMap: integrative genome-wide maps of regulatory motif sites for model species
Authors: Daily Kenneth , Patel Vishal R , Rigor Paul , Xie Xiaohui , Baldi Pierre
Published: December 2011

Background

A central challenge of biology is to map and understand gene regulation on a genome-wide scale. For any given genome, only a small fraction of the regulatory elements embedded in the DNA sequence have been characterized, and there is great interest in developing computational methods to systematically map all these elements and understand their relationships. Such computational efforts, however, are significantly hindered by the overwhelming size of non-coding regions and the statistical variability and complex spatial organizations of regulatory elements and interactions. Genome-wide catalogs of regulatory elements for all model species simply do not yet exist.

Results

The MotifMap system uses databases of transcription factor binding motifs, refined genome alignments, and a comparative genomic statistical approach to provide comprehensive maps of candidate regulatory elements encoded in the genomes of model species. The system is used to derive new genome-wide maps for yeast, fly, worm, mouse, and human. The human map contains 519,108 sites for 570 matrices with a False Discovery Rate of 0.1 or less. The new maps are assessed in several ways, for instance using high-throughput experimental ChIP-seq data and AUC statistics, providing strong evidence for their accuracy and coverage. The maps can be usefully integrated with many other kinds of omic data and are available at http://motifmap.igb.uci.edu/.

Conclusions

MotifMap and its integration with other data provide a foundation for analyzing gene regulation on a genome-wide scale, and for automatically generating regulatory pathways and hypotheses. The power of this approach is demonstrated and discussed using the P53 apoptotic pathway and the Gli hedgehog pathways as examples.
Refinement of Bos taurus sequence assembly based on BAC-FISH experiments
Authors: Partipilo Giulia , D'Addabbo Pietro , Lacalandra Giovanni M , Liu George E , Rocchi Mariano
Published: December 2011

Background

The sequencing of the cow genome was recently published (Btau_4.0 assembly). A second, alternate cow genome assembly (UMD2), based on the same raw sequence data, was also published. The two assemblies have been subsequently updated to Btau_4.2 and UMD3.1, respectively.

Results

We compared the Btau_4.2 and UMD3.1 alternate assemblies. Inconsistencies were grouped into three main categories: (i) DNA segments showing almost coincidental chromosomal mapping but discordant orientation (inversions); (ii) DNA segments showing a discordant map position along the same chromosome; and (iii) sequences present in one chromosomal assembly but absent in the corresponding chromosome of the other assembly. The latter category mainly consisted of large amounts of scaffolds that were unassigned in Btau_4.2 but successfully mapped in UMD3.1. We sampled 70 inconsistencies and identified appropriate cow BACs for each of them. These clones were then utilized in FISH experiments on cow metaphase or interphase nuclei in order to disambiguate the discrepancies. In almost all instances the FISH results agreed with the UMD3.1 assembly. Occasionally, however, the mapping data of both assemblies were discordant with the FISH results.

Conclusions

Our work demonstrates how FISH, which is assembly independent, can be efficiently used to solve assembly problems frequently encountered using the shotgun approach.
Neuroantigen-specific, tolerogenic vaccines: GM-CSF is a fusion partner that facilitates tolerance rather than immunity to dominant self-epitopes of myelin in murine models of experimental autoimmune encephalomyelitis (EAE)
Authors: Abbott Derek J , Blanchfield J Lori , Martinson David A , Russell Sean C , Taslim Najla , Curtis Alan D , Mannie Mark D
Published: December 2011

Background

Vaccination strategies that elicit antigen-specific tolerance are needed as therapies for autoimmune disease. This study focused on whether cytokine-neuroantigen (NAg) fusion proteins could inhibit disease in chronic murine models of experimental autoimmune encephalomyelitis (EAE) and thus serve as potential therapeutic modalities for multiple sclerosis.

Results

A fusion protein comprised of murine GM-CSF as the N-terminal domain and the encephalitogenic MOG35-55 peptide as the C-terminal domain was tested as a tolerogenic, therapeutic vaccine (TTV) in the C57BL/6 model of EAE. Administration of GMCSF-MOG before active induction of EAE, or alternatively, at the onset of EAE blocked the development and progression of EAE. Covalent linkage of the GM-CSF and MOG35-55 domains was required for tolerogenic activity. Likewise, a TTV comprised of GM-CSF and PLP139-151 was a tolerogen in the SJL model of EAE.

Conclusion

These data indicated that fusion proteins containing GM-CSF coupled to myelin auto-antigens elicit tolerance rather than immunity.
Functional coupling analysis suggests link between the obesity gene FTO and the BDNF-NTRK2 signaling pathway
Authors: Rask-Andersen Mathias , Almén Markus Sällman , Olausen Hans R , Olszewski Pawel K , Eriksson Jenny , Chavan Rohit A , Levine Allen S , Fredriksson Robert , Schiöth Helgi B
Published: December 2011

Background

The Fat mass and obesity gene (FTO) has been identified through genome wide association studies as an important genetic factor contributing to a higher body mass index (BMI). However, the molecular context in which this effect is mediated has yet to be determined. We investigated the potential molecular network for FTO by analyzing co-expression and protein-protein interaction databases, Coxpresdb and IntAct, as well as the functional coupling predicting multi-source database, FunCoup. Hypothalamic expression of FTO-linked genes defined with this bioinformatics approach was subsequently studied using quantitative real time-PCR in mouse feeding models known to affect FTO expression.

Results

We identified several candidate genes for functional coupling to FTO through database studies and selected nine for further study in animal models. We observed hypothalamic expression of Profilin 2 (Pfn2), cAMP-dependent protein kinase catalytic subunit beta (Prkacb), Brain derived neurotrophic factor (Bdnf), neurotrophic tyrosine kinase, receptor, type 2 (Ntrk2), Signal transducer and activator of transcription 3 (Stat3), and Btbd12 to be co-regulated in concert with Fto. Pfn2 and Prkacb have previously not been linked to feeding regulation.

Conclusions

Gene expression studies validate several candidates generated through database studies of possible FTO-interactors. We speculate about a wider functional role for FTO in the context of current and recent findings, such as in extracellular ligand-induced neuronal plasticity via NTRK2/BDNF, possibly via interaction with the transcription factor CCAAT/enhancer binding protein β (C/EBPβ).
Conservation of ciliary proteins in plants with no cilia
Authors: Hodges Matthew E , Wickstead Bill , Gull Keith , Langdale Jane A
Published: December 2011

Background

Eukaryotic cilia are complex, highly conserved microtubule-based organelles with a broad phylogenetic distribution. Cilia were present in the last eukaryotic common ancestor and many proteins involved in cilia function have been conserved through eukaryotic diversification. However, cilia have also been lost multiple times in different lineages, with at least two losses occurring within the land plants. Whereas all non-seed plants produce cilia for motility of male gametes, some gymnosperms and all angiosperms lack cilia. During these evolutionary losses, proteins with ancestral ciliary functions may be lost or co-opted into different functions.

Results

Here we identify a core set of proteins with an inferred ciliary function that are conserved in ciliated eukaryotic species. We interrogate this genomic dataset to identify proteins with a predicted ancestral ciliary role that have been maintained in non-ciliated land plants. In support of our prediction, we demonstrate that several of these proteins have a flagellar localisation in protozoan trypanosomes. The phylogenetic distribution of these genes within the land plants indicates evolutionary scenarios of either sub- or neo-functionalisation and expression data analysis shows that these genes are highly expressed in Arabidopsis thaliana pollen cells.

Conclusions

A large number of proteins possess a phylogenetic ciliary profile indicative of ciliary function. Remarkably, many genes with an ancestral ciliary role are maintained in non-ciliated land plants. These proteins have been co-opted to perform novel functions, most likely before the loss of cilia, some of which appear related to the formation of the male gametes.
Down-regulation of HSP70 sensitizes gastric epithelial cells to apoptosis and growth retardation triggered by H. pylori
Authors: Liu Weili , Chen Yan , Lu Gaofeng , Sun Leimin , Si Jianmin
Published: December 2011

Background

H. pylori infection significantly attenuated the expression of HSP70 in gastric mucosal cells. However, the role of HSP70 cancellation in H. pylori-associated cell damages is largely unclear.

Methods

Small interfering RNA (siRNA) was used to down-regulate HSP70 in gastric epithelial cell lines AGS. The transfected cells were then incubated with H. pylori and the functions of HSP70 suppression were observed by viability assay, cell cycle analyses and TUNEL assay. HSP70 target apoptotic proteins were further identified by Western blot.

Results

The inhibition of HSP70 has further increased the effect of growth arrest and apoptosis activation triggered by H. pylori in gastric epithelial cells. The anti-proliferation function of HSP70 depletion was at least by up-regulating p21 and cell cycle modulation with S-phase accumulation. An increase of apoptosis-inducing factor (AIF) and cytosolic cytochrome C contributes to the activation of apoptosis following down-regulation of intracellular HSP70. Extracellular HSP70 increased cellular resistance to apoptosis by suppression the release of AIF and cytochrome c from mitochondria, as well as inhibition of p21 expression.

Conclusions

The inhibition of HSP70 aggravated gastric cellular damages induced by H. pylori. Induction of HSP70 could be a potential therapeutic target for protection gastric mucosa from H. pylori-associated injury.
Assessing the influence of the built environment on physical activity for utility and recreation in suburban metro Vancouver
Authors: Oliver Lisa , Schuurman Nadine , Hall Alexander , Hayes Michael
Published: December 2011

Background

Physical inactivity and associated co-morbidities such as obesity and cardiovascular disease are estimated to have large societal costs. There is increasing interest in examining the role of the built environment in shaping patterns of physical activity. However, few studies have: (1) simultaneously examined physical activity for leisure and utility; (2) selected study areas with a range of built environment characteristics; and (3) assessed the built environment using high-resolution land use data.

Methods

Data on individuals used for this study are from a survey of 1602 adults in selected sites across suburban Metro Vancouver. Four types of physical activity were assessed: walking to work/school, walking for errands, walking for leisure and moderate physical activity for exercise. The built environment was assessed by constructing one-kilometre road network buffers around each respondent's postal code. Measures of the built environment include terciles of recreational and park land, residential land, institutional land, commercial land and land use mix.

Results

Logistic regression analyses showed that walking to work/school and moderate physical activity were not associated with any built environment measure. Living in areas with lower land use mix, lower commercial and lower recreational land increased the odds of low levels of walking for errands. Individuals living in the lower third of land use mix and institutional land were more likely to report low levels of walking for leisure.

Conclusions

These results suggest that walking for errands and leisure have a greater association with the built environment than other dimensions of physical activity.
Antibody degradation in tobacco plants: a predominantly apoplastic process
Authors: Hehle Verena K , Paul Matthew J , Drake Pascal M , Ma Julian KC , van Dolleweerd Craig J
Published: December 2011

Background

Interest in using plants for production of recombinant proteins such as monoclonal antibodies is growing, but proteolytic degradation, leading to a loss of functionality and complications in downstream purification, is still a serious problem.

Results

In this study, we investigated the dynamics of the assembly and breakdown of a human IgG1κ antibody expressed in plants. Initial studies in a human IgG transgenic plant line suggested that IgG fragments were present prior to extraction. Indeed, when the proteolytic activity of non-transgenicNicotiana tabacumleaf extracts was tested against a human IgG1 substrate, little activity was detectable in extraction buffers with pH > 5. Significant degradation was only observed when the plant extract was buffered below pH 5, but this proteolysis could be abrogated by addition of protease inhibitors. Pulse-chase analysis of IgG MAb transgenic plants also demonstrated that IgG assembly intermediates are present intracellularly and are not secreted, and indicates that the majority of proteolytic degradation occurs following secretion into the apoplastic space.

Conclusions

The results provide evidence that proteolytic fragments derived from antibodies of the IgG subtype expressed in tobacco plants do not accumulate within the cell, and are instead likely to occur in the apoplastic space. Furthermore, any proteolytic activity due to the release of proteases from subcellular compartments during tissue disruption and extraction is not a major consideration under most commonly used extraction conditions.
Synthesis of silicalite-poly(furfuryl alcohol) composite membranes for oxygen enrichment from air
Authors: He Li , Li Dan , Wang Kun , Suresh Akkihebbal K , Bellare Jayesh , Sridhar Tam , Wang Huanting
Published: December 2011

Silicalite-poly(furfuryl alcohol) [PFA] composite membranes were prepared by solution casting of silicalite-furfuryl alcohol [FA] suspension on a porous polysulfone substrate and subsequent in situ polymerization of FA. X-ray diffraction, nitrogen sorption, thermogravimetric analysis, scanning electron microscopy, and energy-dispersive X-ray spectroscopy were used to characterize silicalite nanocrystals and silicalite-PFA composite membranes. The silicalite-PFA composite membrane with 20 wt.% silicalite loading exhibits good oxygen/nitrogen selectivity (4.15) and high oxygen permeability (1,132.6 Barrers) at 50°C. Silicalite-PFA composite membranes are promising for the production of oxygen-enriched air for various applications.