The PI3K–NF-κB signal transduction pathway is involved in mediating the anti-inflammatory effect of IB-MECA in adjuvant-induced arthritis

The anti-inflammatory effect of adenosine was previously found to be mediated via activation of the A(3 )adenosine receptor (A(3)AR). The aim of the present study was to decipher the molecular mechanism involved with the inhibitory effect of IB-MECA, an A(3)AR agonist, on adjuvant-induced arthritis. The adjuvant-induced arthritis rats responded to IB-MECA treatment with a decrease in the clinical score and the pathological score of the disease. The response to IB-MECA was neutralized by the antagonist MRS 1220, confirming that the efficacy of the synthetic agonist was A(3)AR mediated. The A(3)AR protein expression level was highly expressed in the synovia, in the peripheral blood mononuclear cells and in the drain lymph node (DLN) tissues of adjuvant-induced arthritis rats in comparison with naïve animals. Downregulation of A(3)AR expression was noted upon treatment with IB-MECA. Analysis of synovia and DLN protein extracts revealed a decreased expression level of PI3K, PKB/Akt, IKK, NF-κB and tumor necrosis factor alpha, known to affect survival and apoptosis of inflammatory cells, whereas the caspase-3 level was upregulated. Taken together, high A(3)AR expression is found in the synovia, in the immune cells in the DLN and in peripheral blood mononuclear cells. IB-MECA, an orally bioavailable molecule, activates the A(3)AR, inducing receptor downregulation and the initiation of a molecular mechanism that involves de-regulation of the PI3K–NF-κB signaling pathway. As a result, a potent anti-inflammatory effect manifested in the improvement of the disease clinical score and pathological score occurs. The finding that the A(3)AR expression level in the peripheral blood mononuclear cells and in the DLN reflects the receptor status in the remote inflammatory site suggests use of the A(3)AR as a follow-up biomarker

Identifying Opportunities in Citizen Science for Academic Libraries

Citizen science projects continue to grow in popularity, providing opportunities for non-expert volunteers to contribute to and become personally invested in rigorous scientific research. Academic libraries, aiming to promote and provide tools and resources to master scientific and information literacy, can support these efforts. While few examples currently exist of academic libraries involved in citizen science, this article identifies potential roles in community building; data curation; scholarly communication reform; and provision of space, technology, and resources

Mouse Dendritic Cells Pulsed with Capsular Polysaccharide Induce Resistance to Lethal Pneumococcal Challenge: Roles of T Cells and B Cells

Mice are exceedingly sensitive to intra-peritoneal (IP) challenge with some virulent pneumococci (LD50 = 1 bacterium). To investigate how peripheral contact with bacterial capsular polysaccharide (PS) antigen can induce resistance, we pulsed bone marrow dendritic cells (BMDC) of C57BL/6 mice with type 4 or type 3 PS, injected the BMDC intra-foot pad (IFP) and challenged the mice IP with supra-lethal doses of pneumococci. We examined the responses of T cells and B cells in the draining popliteal lymph node and measured the effects on the bacteria in the peritoneum and blood. We now report that: 1) The PS co-localized with MHC molecules on the BMDC surface; 2) PS-specific T and B cell proliferation and IFNγ secretion was detected in the draining popliteal lymph nodes on day 4; 3) Type-specific resistance to lethal IP challenge was manifested only after day 5; 4) Type-specific IgM and IgG antibodies were detected in the sera of only some of the mice, but B cells were essential for resistance; 5) Control mice vaccinated with a single injection of soluble PS did not develop a response in the draining popliteal lymph node and were not protected; 6) Mice injected with unpulsed BMDC also did not resist challenge: In unprotected mice, pneumococci entered the blood shortly after IP inoculation and multiplied exponentially in both blood and peritoneum killing the mice within 20 hours. Mice vaccinated with PS-pulsed BMDC trapped the bacteria in the peritoneum. The trapped bacteria proliferated exponentially IP, but died suddenly at 18–20 hours. Thus, a single injection of PS antigen associated with intact BMDC is a more effective vaccine than the soluble PS alone. This model system provides a platform for studying novel aspects of PS-targeted vaccination

A Systems Immunology Approach to the Host-Tumor Interaction: Large-Scale Patterns of Natural Autoantibodies Distinguish Healthy and Tumor-Bearing Mice

Traditionally, immunology has considered a meaningful antibody response to be marked by large amounts of high-affinity antibodies reactive with the specific inciting antigen; the detection of small amounts of low-affinity antibodies binding to seemingly unrelated antigens has been considered to be beneath the threshold of immunological meaning. A systems-biology approach to immunology, however, suggests that large-scale patterns in the antibody repertoire might also reflect the functional state of the immune system. To investigate such global patterns of antibodies, we have used an antigen-microarray device combined with informatic analysis. Here we asked whether antibody-repertoire patterns might reflect the state of an implanted tumor. We studied the serum antibodies of inbred C57BL/6 mice before and after implantation of syngeneic 3LL tumor cells of either metastatic or non-metastatic clones. We analyzed patterns of IgG and IgM autoantibodies binding to over 300 self-antigens arrayed on slides using support vector machines and genetic algorithm techniques. We now report that antibody patterns, but not single antibodies, were informative: 1) mice, even before tumor implantation, manifest both individual and common patterns of low-titer natural autoantibodies; 2) the patterns of these autoantibodies respond to the growth of the tumor cells, and can distinguish between metastatic and non-metastatic tumor clones; and 3) curative tumor resection induces dynamic changes in these low-titer autoantibody patterns. The informative patterns included autoantibodies binding to self-molecules not known to be tumor-associated antigens (including insulin, DNA, myosin, fibrinogen) as well as to known tumor-associated antigens (including p53, cytokeratin, carbonic anhydrases, tyrosinase). Thus, low-titer autoantibodies that are not the direct products of tumor-specific immunization can still generate an immune biomarker of the body-tumor interaction. System-wide profiling of autoantibody repertoires can be informative

See also Young 1971: Marshall McLuhan, moral panics and moral indignation

Despite the fact that he introduced the concept into the sociology of deviance, Jock Young never claimed ownership of ‘moral panic’. There is little to no evidence suggest that he felt the need to keep up with the burgeoning literature on ‘moral panics studies’; rather, in much of this literature, his name is all but invisible, reduced to ‘See also Young, 1971’. This essay begins with a review of Jock Young’s original use of ‘moral panic’ before discussing how he subsequently rejected the term, and then reflecting on why and how he re-engaged with it. My position is that Jock Young was ambivalent about how the term was subsequently developed and transformed into what he viewed as: an incredulous ‘left idealist’ reaction to morally challenging issues; a mechanical sociological model used to decide on whether something was or was not a ‘boil-in-the-bag’ moral panic; and finally a dismissive journalistic judgement. In all these ‘moral panic for dummies’ usages, for Young, the volatile energizing moral dynamics of ‘action + reaction’ have been lost as has his nuanced appreciation of the shifting cultural significance of moral panic. Perhaps most significantly, the core dynamic of ‘moral indignation’ and its channelling—concerns that are present in all of Jock Young’s work—have likewise been lost in common usage of moral panic

Stellar mass loss and the Intra-Cluster Medium in Galactic globular clusters: a deep radio survey for HI and OH

We present the results of a survey, the deepest to date, for HI emission at 21 cm and OH emission at 18 cm (lines at 1612, 1665, 1667 and 1720 MHz) in the direction towards the Galactic globular clusters M 15, M 2, NGC 6934, NGC 7006 and Pal 13. The aim is to measure the amount of hydrogen in the intra-cluster medium (ICM), and to find OH masers in the circumstellar envelopes of globular cluster red giants. We present a tentative detection of 0.3 Msun of neutral hydrogen in M 15 and possible detections of neutral hydrogen in M 2 and Pal 13. We derive upper limits to the neutral hydrogen content of NGC 6934 and NGC 7006. No OH emission is detected. We also present deep HI data of the northern tip of the Magellanic Stream behind Pal 13.Comment: Accepted for publication in MNRAS. 7 page

‘Communities of resistance’ and the use of newspaper discussion boards Polish workers in Japanese foreign investments

This is the peer reviewed version of the following article: Maciej Bancarzewski, and Jane Hardy, ‘‘Communities of resistance’ and the use of newspaper discussion boards: Polish workers in Japanese foreign investments’, New Technology, Work and Employment, Vol. 32 (2): 160-173, July 2017, which has been published in final form at https://doi.org/10.1111/ntwe.12091. Under embargo until 25 July 2019. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.This article examines the content of two hundred posts on newspaper discussion boards by workers in a cluster of Japanese foreign investments in Poland. The conclusions are first, that the material experiences of workers generate a set of themes in relation to the labour process with regard to wages and working conditions, bullying and monitoring that exhibit similarities across countries. Second, we argue that an analysis of the discourse used is shaped by political and institutional conditions, which reveal national differences in how workers perceive and locate their exploitation. Finally, in relation to debates about workers’ resistance and the use of the internet we argue that the interaction of themes related to the material experience of work are intertwined with institutionally embedded understandings of exploitation, which not only enable a shared framework for venting, but also provide the basis for a community of resistance.Peer reviewedFinal Accepted Versio