bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estradiol Suppresses NF-κB Activation through Coordinated Regulation of let-7a and miR-125b in Primary Human Macrophages
Authors: Murphy Amy J. , Guyre Paul M. , Pioli Patricia A. 
Published: March 2010

Abstract
Previous findings suggest that 17β-estradiol (estradiol) has a suppressive effect on TNF-α, but the mechanism by which estradiol regulates TNF-α expression in primary human macrophages is unknown. In this article, we demonstrate that pretreatment of human macrophages with estradiol attenuates LPS-induced TNF-α expression through the suppression of NF-κB activation. Furthermore, we show that activation of macrophages with LPS decreases the expression of κB-Ras2, an inhibitor of NF-κB signaling. Estradiol pretreatment abrogates this decrease, leading to the enhanced expression of κB-Ras2 with LPS stimulation. Additionally, we identified two microRNAs, let-7a and miR-125b, which target the κB-Ras2 3′ untranslated region (UTR). LPS induces let-7a and inhibits miR-125b expression in human macrophages, and pretreatment with estradiol abrogates these effects. 3′UTR reporter assays demonstrate that let-7a destabilizes the κB-Ras2 3′UTR, whereas miR-125b enhances its stability, resulting in decreased κB-Ras2 in response to LPS. Our data suggest that pretreatment with estradiol reverses this effect. We propose a novel mechanism for estradiol inhibition of LPS-induced NF-κB signaling in which κB-Ras2 expression is induced by estradiol via regulation of let-7a and miR-125b. These findings are significant in that they are the first to demonstrate that estradiol represses NF-κB activation through the induction of κB-Ras2, a key inhibitor of NF-κB signaling.
Premature Terminal Exhaustion of Friend Virus-Specific Effector CD8+ T Cells by Rapid Induction of Multiple Inhibitory Receptors
Authors: Takamura Shiki , Tsuji-Kawahara Sachiyo , Yagita Hideo , Akiba Hisaya , Sakamoto Mayumi , Chikaishi Tomomi , Kato Maiko , Miyazawa Masaaki 
Published: March 2010

Abstract
During chronic viral infection, persistent exposure to viral Ags leads to the overexpression of multiple inhibitory cell-surface receptors that cause CD8+ T cell exhaustion. The severity of exhaustion correlates directly with the level of infection and the number and intensity of inhibitory receptors expressed, and it correlates inversely with the ability to respond to the blockade of inhibitory pathways. Friend virus (FV) is a murine retrovirus complex that induces acute high-level viremia, followed by persistent infection and leukemia development, when inoculated into immunocompetent adult mice. In this article, we provide conclusive evidence that FV infection results in the generation of virus-specific effector CD8+ T cells that are terminally exhausted. Acute FV-induced disease is characterized by a rapid increase in the number of virus-infected erythroblasts, leading to massive splenomegaly. Most of the expanded erythroblasts strongly express programmed death ligand-1 and MHC class I, thereby creating a highly tolerogenic environment. Consequently, FV-specific effector CD8+ T cells uniformly express multiple inhibitory receptors, such as programmed cell death 1 (PD-1), T cell Ig domain and mucin domain 3 (Tim-3), lymphocyte activation gene-3, and CTLA-4, rapidly become nonresponsive to restimulation and are no longer reinvigorated by combined in vivo blockade of PD-1 and Tim-3 during the memory phase. However, combined blockade of PD-1 and Tim-3 during the priming/differentiation phase rescued FV-specific CD8+ T cells from becoming terminally exhausted, resulting in improved CD8+ T cell functionality and virus control. These results highlight FV’s unique ability to evade virus-specific CD8+ T cell responses and the importance of an early prophylactic approach for preventing terminal exhaustion of CD8+ T cells.
Notch2 Signaling Is Required for Potent Antitumor Immunity In Vivo
Authors: Sugimoto Koji , Maekawa Yoichi , Kitamura Akiko , Nishida Jun , Koyanagi Akemi , Yagita Hideo , Kojima Hidefumi , Chiba Shigeru , Shimada Mitsuo , Yasutomo Koji 
Published: March 2010

Abstract
CD8+ T cells play a central role in cancer immunosurveillance, and the efficient induction of CTLs against tumor Ags is required for successful immunotherapy for cancer patients. Notch signaling directly regulates the transcription of effector molecules in CTLs. However, it remains unclear whether Notch signaling in CD8+ T cells is required for antitumor CTL responses and whether modulation of Notch signaling can augment antitumor CTL responses. In this study, we demonstrate that signaling by Notch2 but not Notch1 in CD8+ T cells is required for antitumor CTL responses. Notch2flox/flox mice crossed with E8I-cre transgenic (N2F/F-E8I) mice, in which the Notch2 gene is absent only in CD8+ T cells, die earlier than control mice after inoculation with OVA-expressing EG7 thymoma cells. In contrast, Notch1flox/flox mice crossed with E8I-cre transgenic mice inoculated with EG7 cells die comparable to control mice, indicating that Notch2 is crucial for exerting antitumor CTL responses. Injection of anti-Notch2 agonistic Ab or delta-like 1-overexpressing dendritic cells augmented the antitumor response in C57BL/6 mice inoculated with EG7 cells. These findings indicate that Notch2 signaling in CD8+ T cells is required for generating potent antitumor CTLs, thus providing a crucial target for augmenting tumor immune responses.
Activation of Naive NK Cells in Response toListeria monocytogenesRequires IL-18 and Contact with Infected Dendritic Cells
Authors: Humann Jessica , Lenz Laurel L. 
Published: March 2010

AbstractThe mechanisms for NK cell activation during infection by intracellular bacterial pathogens are not clearly defined. To dissect how Listeria monocytogenes infection elicits NK cell activation, we evaluated the requirements for activation of naive splenic NK cells by infected bone marrow-derived dendritic cells (BMDCs). We found that NK cell activation in this setting required infection of BMDCs by live wild type bacteria. NK cells were not activated when BMDCs were infected with a live hemolysin deficient (Δhly) strain. Neutralization of IL-12, TNF-α, or caspase-1 each dramatically reduced NK cell IFN-γ production in response to live wt L. monocytogenes infection. Addition of recombinant IL-18, but not IL-1β, reversed the effects of caspase-1 inhibition. Recombinant IL-18 also restored NK cell activation by BMDCs infected with Δhly L. monocytogenes, which produced IL-12 but not IL-18. IL-18 acted on NK cells because MyD88 expression was required in responding NK cells, but not infected BMDC. However, secreted cytokines were not sufficient for activation of naive NK cells by infected BMDCs. Rather, NK cell activation additionally required contact between infected BMDCs and NK cells. These data suggest that the activation of NK cells during L. monocytogenes infection requires both secreted cytokines and ligation of NK activating receptors during direct contact with infected DCs.
IL-17 Enhancement of the IL-6 Signaling Cascade in Astrocytes
Authors: Ma Xiangyu , Reynolds Stephanie L. , Baker Brandi J. , Li Xingang , Benveniste Etty N. , Qin Hongwei 
Published: March 2010

Abstract
Astrocytes have important physiological roles in CNS homeostasis and serve as a bridge between the CNS and immune system. IL-17 and IL-6 are important in many CNS disorders characterized by neuroinflammation. We examined the role of IL-17 on the IL-6 signaling cascade in primary astrocytes. IL-17 functioned in a synergistic manner with IL-6 to induce IL-6 expression in astrocytes. The synergistic effect involved numerous signaling pathways including NF-κB, JNK MAPK, and p38 MAPK. The NF-κB pathway inhibitor BAY-11, JNK inhibitor JNKi II, and p38 inhibitor SB203580 suppressed the synergistic effect of IL-6 and IL-17 on IL-6 expression. IL-17 synergized with IL-6 to enhance the recruitment of activated NF-κB p65, c-Fos, c-Jun, and the histone acetyltransferases CREB-binding protein and p300 to the IL-6 promoter in vivo to induce IL-6 transcription. This was accompanied by enhanced acetylation of histones H3 and H4 on the IL-6 promoter. Moreover, we elucidated an important role for suppressor of cytokine signaling (SOCS) 3 in IL-17 enhancement of IL-6 signaling in astrocytes. SOCS3 small interfering RNA knockdown and SOCS3 deletion in astrocytes augmented the synergistic effect of IL-6 and IL-17 due to an enhancement of activation of the NF-κB and MAPK pathways. These results indicate that astrocytes can serve as a target of Th17 cells and IL-17 in the CNS, and SOCS3 participates in IL-17 functions in the CNS as a negative feedback regulator.
Evidence for a TCR Affinity Threshold Delimiting Maximal CD8 T Cell Function
Authors: Schmid Daphné A. , Irving Melita B. , Posevitz Vilmos , Hebeisen Michael , Posevitz-Fejfar Anita , Sarria J-C. Floyd , Gomez-Eerland Raquel , Thome Margot , Schumacher Ton N. M. , Romero Pedro , Speiser Daniel E. , Zoete Vincent , Michielin Olivier , Rufer Nathalie 
Published: March 2010

Abstract
Protective adaptive immune responses rely on TCR-mediated recognition of Ag-derived peptides presented by self-MHC molecules. However, self-Ag (tumor)-specific TCRs are often of too low affinity to achieve best functionality. To precisely assess the relationship between TCR–peptide–MHC binding parameters and T cell function, we tested a panel of sequence-optimized HLA-A*0201/NY–ESO-1157–165–specific TCR variants with affinities lying within physiological boundaries to preserve antigenic specificity and avoid cross-reactivity, as well as two outliers (i.e., a very high- and a low-affinity TCR). Primary human CD8 T cells transduced with these TCRs demonstrated robust correlations between binding measurements of TCR affinity and avidity and the biological response of the T cells, such as TCR cell-surface clustering, intracellular signaling, proliferation, and target cell lysis. Strikingly, above a defined TCR–peptide–MHC affinity threshold (KD &lt; ∼5 μM), T cell function could not be further enhanced, revealing a plateau of maximal T cell function, compatible with the notion that multiple TCRs with slightly different affinities participate equally (codominantly) in immune responses. We propose that rational design of improved self-specific TCRs may not need to be optimized beyond a given affinity threshold to achieve both optimal T cell function and avoidance of the unpredictable risk of cross-reactivity.
Negotiating ‘Normal’: The Management of Feminine Identities in Rural Britain
Authors: Gill Fiona 
Published: March 2010

This paper examines the management of feminine identities in a women's rugby team in a rural British community. In so doing, the issue of new, and potentially problematic, forms of femininity are explored, with their attendant social consequences. The team, known as the Jesters, is situated in a social context which is dominantly masculine and heterosexist, with rigidly enforced gender roles. Due to their participation in rugby, a ‘man's game’, the Jesters are threatened with marginalisation for their apparent failure to conform to, and potential disruption of, established gender norms. This threat is managed through the performance of certain ‘inauthentic’ feminine identities (hyper-femininity and heterosexuality) on the part of the entire team. It is this ‘team identity’ which lies at the heart of this paper. This paper therefore examines the group dynamics of identity performance and negotiation. In negotiating ‘normal’ the Jesters are forced to confront changing gender norms and social contexts within the team itself. This paper also examines the difficulties faced by individuals when their own interests are opposed to the interests of the group of which they are a part. Although largely uncaring about the private lives of team members, the heterosexual members of the Jesters refuse to tolerate the performance of alternative versions of femininity when it may result in the exclusion of the team as a whole. This paper therefore examines the differing interests of heterosexual and lesbian femininities within a potentially marginalised group and some of the coping mechanisms adopted by both groups to develop a coherent team image.
Sociological Engagements with Computing: The Advent of E-Science and Some Implications for the Qualitative Research Community
Authors: Hodgson Susan M. , Clark Tom 
Published: March 2010

This paper explores some of the implications for qualitative researchers within sociology of developments in Grid technology and thereby aims to contribute to the debate on the future of sociological research in an increasingly digitised world. The well-established field of humanities computing provides an interesting counterpoint. We use the methodological techniques of ‘secondary analysis’ and ‘visual research’, two currently marginal approaches within sociological research but with huge potential within e-environments, as lenses through which the potentials and pitfalls of Grid-supported qualitative work might be anticipated. Rather than a concern with the technical however, we argue for a concurrent attention to the methodological in relation to technological developments. We find that current developments in the qualitative field are more in line with the interests of the humanities and this may shape and constrain the research that sociologists could do. Also, that the conditions to support innovative sociological developments for qualitative Grid computing are not currently well developed or supported. We conclude that in order for a more progressive e-social science agenda to emerge, a broader constituency of sociological researchers should engage with the technological debate, otherwise we risk missing out on opportunities to shape emerging technologies to our research needs.
Collective Representations, Divided Memory and Patterns of Paradox: Mining and Shipbuilding
Authors: Roberts Ian 
Published: March 2010

This paper seeks to examine the different relationship of two industries to their potential for representation and celebration in collective memory. Looking at case studies of mining and shipbuilding in the shared location of Wearside the paper compares and contrasts features of the two industries in relation to the divergent outcomes of the traces of their collective memory in this place. Using visual representations the paper makes the case that the mining industry has experienced a successful recovery of memory. This is contrasted to the paucity of visual representation in relation to shipbuilding. The reasons for the contrast in the viability of collective memory are examined. Material, cultural and aesthetic issues are addressed. Contrasts are drawn between divisions of labour in the two industries and the ways in which these impact upon community and trade union organisation which further relate to the contrast between industrial and occupational identity. Differences in the legacy of the physical occupational communities of the two industries are illustrated. There is also an examination of the aesthetic forms of representation in which mining is seen as characterised by the aesthetics of labour, whereas shipbuilding is represented more through the aesthetics of product. The way in which the industries were closed also becomes important to understand the variation in the differences of the potential of collective memory. All of these strands are brought together to conclude that in relation to the potential for collective memory, mining can be seen to have gone through a process of ‘mourning’ whereas melancholia seems to more adequately represent the situation with respect to shipbuilding. In illustrating these cases the paper is arguing for a more sophisticated understanding of the process of deindustrialisation and the potential for the recovery of collective memory.
The Online Student: Lurking, Chatting, Flaming and Joking
Authors: Orton-Johnson Kate 
Published: March 2010

This paper looks at the use of online conference interaction as a part of a web-based distance-learning course. There has been much debate surrounding the potential of educational technology, particularly online conference interaction, to support teaching and learning yet little attention has been paid to student experiences and understandings of the online learning environment. Drawing on data from auto-ethnographic fieldwork the paper identifies 5 categories of participation in asynchronous online conferences: lurker participation, member participation, expert/experienced participation, flamer participation and joker participation. Through an exploration of these forms of participation the paper attempts to understand and illustrate the complexities and contradictions of situating conference interaction alongside the demands of study. The analysis highlights the role of online conferencing as a space for ‘interaction work’ distinct and separated from existing repertoires of formal study. The paper concludes by suggesting that pedagogically successful use of conferences as part of distance learning needs to understand the challenges and demands of remediating existing practices.
Method in a Photographic Enquiry of being Deaf
Authors: Thoutenhoofd E. 
Published: March 2010

What follows is based on the hypothesis that aspects of a particular, socially and culturally distinct, visuality [1] are manifest in visual data such as photographs. I will explore this hypothesis with reference to Deaf people, people who use sign language and who are members of the Deaf community, using data from earlier research (Thoutenhoofd, 1996). To this end, I have opted for two parallel texts, a photographic one as well as a written one, cross-referenced by hyperlinks. The photographs form the core, or the ‘evidence’ of the method outlined in the text. The photographs portray a number of pertinent visual characteristics and strategies found where Deaf people congregate into clearly defined communities, for example Deaf clubs, d/Deaf colleges, and in the pages of magazines aimed at d/Deaf audiences; yet the photographs bear witness to the commonplace, portraying regular Deaf club and Deaf college activities. In the process of discussing the reasons for taking the photographs and having photographs taken, I set out to describe what is meant by a ‘Deaf visuality’, and to suggest its relevance to research into deafness and being d/Deaf.
Social Work, Risk, Power
Authors: Smith Roger 
Published: March 2010

Contemporary ideas and strategies of both ‘risk’ and ‘power’ are significant and dynamic influences in social theory and social action, and they can therefore be expected to have a substantial impact on the ways in which social work is constituted, practiced and evaluated. In this article, I shall articulate distinct conceptualisations and debates about each of these, before considering their inter-relationships and the implications of these for our thinking about what social work is, and what it should be. Firstly, I will consider social work's contested and problematic place within the broader welfare domain. It is recognised as being a form of activity which inhabits an ambiguous and uncertain position at the interface between the individual and the social, and between the marginalised and the mainstream. Building on this, ‘power’ will be shown to infuse social work ideas and practices in a number of distinct dimensions, linking and bridging ‘personal’, ‘positional’ and ‘relational’ domains. This discussion will be juxtaposed with a discussion of ‘risk’ and the part it has come to play in shaping and infusing social work practices, especially but not exclusively with children. The deconstruction of contemporary understandings and uses of risk as a central and ‘authoritative’ feature of assessment and decision-making will inform the argument that it can be viewed as a vehicle for the maintenance and legitimation of power relations which disenfranchise and oppress those who are most vulnerable. In conclusion, I will summarise the ways in which conventional understandings and inter-related material realities of power and risk are often hierarchical, uni-directional and oppressive; and on this basis, how they can be laid open to challenge. The reconceptualisation and remaking of power relations will be shown to have direct consequences for the ways in which risk is defined and addressed as a social work ‘problem’.
Modelling Tabular Data with an Ordered Outcome
Authors: Gayle Vernon 
Published: March 2010

A large amount of data that is considered within sociological studies consists of categorical variables that lend themselves to tabular analysis. In the sociological analysis of data regarding social class and educational attainment, for example, the variables of interest can often plausibly be considered as having a substantively interesting order. Standard log-linear models do not take ordinality into account, thereby potentially they may disregard useful information. Analyzing tables where the response variable has ordered categories through model building has been problematic in software packages such as GLIM (Aitken et al., 1989). Recent developments in statistical modelling have offered new possibilities and this paper explores one option, namely the continuation ratio model which was initially reported by Fienberg and Mason (1979). The fitting of this model to data in tabular form is possible in GLIM although not especially trivial and by and large this approach has not been employed in sociological research. In this paper I outline the continuation ratio model and comment upon how it can be fitted to data by sociologists using the GLIM software. In addition I present a short description of the relative merits of such an approach. Presenting this paper in an electronic format facilitates the possibility of replicating the analysis. The data is appended to the paper in the appropriate format along with a copy of the GLIM transcript. A dumped GLIM4 file is also attached.
Living Alone: Its Place in Household Formation and Change
Authors: Chandler Joan , Williams Malcolm , Maconachie Moira , Collett Tracey , Dodgeon Brian 
Published: March 2010

In recent decades there has been a significant rise in the numbers of people who live alone and it was predicted that by 2002 that a third of all households will be single-person households. The predicted increase has occurred with indications of continued growth in this type of living arrangement. Furthermore, although living alone remains common among older age groups, the largest growth has been within younger populations. This demographic trend has attracted speculation about the numbers of people who will experience solo living, the stability of living alone in people's biography, and the impact of gender differences in the likelihood and stability of living alone. To answers these questions, this paper uses longitudinally linked Census data from England and Wales to explore the household origins and household destinations of working age people who live alone. This longitudinal data derives from the 1971, 1981 and 1991 Censuses. The data from this analysis confirms other research demonstrating the increasingly numbers of non-retired people who live alone. Furthermore it demonstrates that once a person lives alone, they are more likely to continue to live in that household arrangement than any other and that the tendency to live alone and to continue to live alone is more likely amongst younger cohorts of people. It also demonstrates that the largest increase in living alone in amongst men, but that once women live alone they are more likely to continue to live alone. These findings have an important bearing on current debates about ‘individualisation’, the contemporary experience of family life, life course trajectories and the emergent life styles of younger populations.