The Impact of Motivation, Processing Difficulty and Cognitive Resources on the Use of Base-Rates in Social Judgment

This study explores the impact of motivation, cognitive resources and difficulty of processing on social judgment. We hypothesized and found all three variables influence the type of information used to render judgment. Only when the information was easy to process, cognitive resources were ample and motivation was high were subjects able to use difficult information as a basis for their judgment. Furthermore, contrary to the common notion that statistical information tends to be utilized when resources are high, we were able to show that subjects relied on statistical information when their motivation was low, the information was difficult to process and/or cognitive resources were limited. These results add to the growing body of evidence attesting that the contents of information as such do not affect the likelihood of their being made use of in judgment. Both base-rates and representativeness ("heuristic") information seem to be used in accordance with their subjective relevance - when such relevance is discerned given that the individuals' resources are sufficient to cope with the difficult posed by the cognitive task at hand

Whose Fault Is it Anyway? Political Orientation, Attributions of Responsibility, and Support for the War in Iraq

Political orientation has been shown to be a strong predictor of attitudes toward war. Specifically, political conservatism has been associated with increased support for war and with decreased attribution of responsibility for war to one's own government. The present research aims to test whether the relationship between political orientation and support for the war in Iraq is mediated by attributions of government responsibility. In Study 1, survey data showed that the relationship between political orientation and support for the Iraq war was mediated by beliefs about the US government's motivations for the war. Study 2 provided a conceptual replication of the proposed mediation model and extended the findings from beliefs about US government motivations to perceived threat from the pre-war Iraqi government. Study 3 used an experimental paradigm to manipulate perceived threat to show that such beliefs directly affected support for the war. Implications and directions for future research are discusse

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

Methotrexate enhances the anti-inflammatory effect of CF101 via up-regulation of the A(3 )adenosine receptor expression

Methotrexate (MTX) exerts an anti-inflammatory effect via its metabolite adenosine, which activates adenosine receptors. The A(3 )adenosine receptor (A(3)AR) was found to be highly expressed in inflammatory tissues and peripheral blood mononuclear cells (PBMCs) of rats with adjuvant-induced arthritis (AIA). CF101 (IB-MECA), an A(3)AR agonist, was previously found to inhibit the clinical and pathological manifestations of AIA. The aim of the present study was to examine the effect of MTX on A(3)AR expression level and the efficacy of combined treatment with CF101 and MTX in AIA rats. AIA rats were treated with MTX, CF101, or both agents combined. A(3)AR mRNA, protein expression and exhibition were tested in paw and PBMC extracts from AIA rats utilizing immunohistochemistry staining, RT-PCR and Western blot analysis. A(3)AR level was tested in PBMC extracts from patients chronically treated with MTX and healthy individuals. The effect of CF101, MTX and combined treatment on A(3)AR expression level was also tested in PHA-stimulated PBMCs from healthy individuals and from MTX-treated patients with rheumatoid arthritis (RA). Combined treatment with CF101 and MTX resulted in an additive anti-inflammatory effect in AIA rats. MTX induced A(2A)AR and A(3)AR over-expression in paw cells from treated animals. Moreover, increased A(3)AR expression level was detected in PBMCs from MTX-treated RA patients compared with cells from healthy individuals. MTX also increased the protein expression level of PHA-stimulated PBMCs from healthy individuals. The increase in A(3)AR level was counteracted in vitro by adenosine deaminase and mimicked in vivo by dipyridamole, demonstrating that receptor over-expression was mediated by adenosine. In conclusion, the data presented here indicate that MTX induces increased A(3)AR expression and exhibition, thereby potentiating the inhibitory effect of CF101 and supporting combined use of these drugs to treat RA

Methotrexate enhances the anti-inflammatory effect of CF101 via up-regulation of the A(3 )adenosine receptor expression

Methotrexate (MTX) exerts an anti-inflammatory effect via its metabolite adenosine, which activates adenosine receptors. The A(3 )adenosine receptor (A(3)AR) was found to be highly expressed in inflammatory tissues and peripheral blood mononuclear cells (PBMCs) of rats with adjuvant-induced arthritis (AIA). CF101 (IB-MECA), an A(3)AR agonist, was previously found to inhibit the clinical and pathological manifestations of AIA. The aim of the present study was to examine the effect of MTX on A(3)AR expression level and the efficacy of combined treatment with CF101 and MTX in AIA rats. AIA rats were treated with MTX, CF101, or both agents combined. A(3)AR mRNA, protein expression and exhibition were tested in paw and PBMC extracts from AIA rats utilizing immunohistochemistry staining, RT-PCR and Western blot analysis. A(3)AR level was tested in PBMC extracts from patients chronically treated with MTX and healthy individuals. The effect of CF101, MTX and combined treatment on A(3)AR expression level was also tested in PHA-stimulated PBMCs from healthy individuals and from MTX-treated patients with rheumatoid arthritis (RA). Combined treatment with CF101 and MTX resulted in an additive anti-inflammatory effect in AIA rats. MTX induced A(2A)AR and A(3)AR over-expression in paw cells from treated animals. Moreover, increased A(3)AR expression level was detected in PBMCs from MTX-treated RA patients compared with cells from healthy individuals. MTX also increased the protein expression level of PHA-stimulated PBMCs from healthy individuals. The increase in A(3)AR level was counteracted in vitro by adenosine deaminase and mimicked in vivo by dipyridamole, demonstrating that receptor over-expression was mediated by adenosine. In conclusion, the data presented here indicate that MTX induces increased A(3)AR expression and exhibition, thereby potentiating the inhibitory effect of CF101 and supporting combined use of these drugs to treat RA

Social Exclusion and the Choice of Important Groups

Social connections are fundamental to our existence. As a result, social exclusion is a painful and distressing experience. When belonging is thwarted, people seek inclusion which can be achieved through group membership. Thus, excluded individuals and/or those whose need to belong is particularly strong will be particularly motivated to join groups. Moreover, to the extent that the need to belong is satisfied by closeness with other group members, and closeness is a feature of group cohesion, excluded individuals or ones with a strong need to belong are likely to be attracted to highly cohesive groups. Finally, the subjective importance of a group to its members should determine the degree of perceived cohesion. Importance of a group is defined as the group's centrality to individuals' social identity. The more central a given dimension is to one's identity, the greater the attraction to individuals sharing that dimension (Byrne, 1961). Hence, the more important the group, the greater the attraction of the members to each other, defining group cohesion. Ultimately then, the greater the individuals' prior experience of exclusion or the greater their need to belong, the greater their motivation should be to join important (vs. less important) groups. These notions are investigated in the present dissertation. A review of the literature on social exclusion and the similarity-attraction hypothesis is presented followed by two studies showing that, both in the lab and in the real world, individuals who have been socially excluded want to join and/or feel more connected to important groups

Should long-term climate change adaptation be focused on smallholders?

Smallholder agriculture employs the majority of the global poor and produces substantial shares of food in developing countries while also being highly vulnerable to environmental change. This makes it a focus of numerous policies for increased productivity and climate change adaptation. Given demographic and economic processes that are likely to reduce smallholder prevalence, how justified is this focus from a long-term perspective? We estimate future global smallholder distributions using historical trends and demographic projections and calculate indices of its future share of climate change impacts. While past trends of decreasing farm size are likely to reverse in Asia and slow down in Africa, we project smallholders will continue to occupy substantial shares of rural populations and cultivated land and bear a sizable portion of climate change impacts, amounting for about 33% (25%) of an index of human exposure to 1 °C (2 °C) warming. However, increased economic possibilities in rural areas can rapidly attenuate these assessments

Inhibition of IL-17 and IL-23 in Human Keratinocytes by the A3 Adenosine Receptor Agonist Piclidenoson

Interleukin-17 and interleukin-23 play major roles in the inflammatory process in psoriasis. The Gi protein-associated A3 adenosine receptor (A3AR) is known to be overexpressed in inflammatory cells and in peripheral blood mononuclear cells (PBMCs) of patients with autoimmune inflammatory conditions. Piclidenoson, a selective agonist at the A3AR, induces robust anti-inflammatory effect in psoriasis patients. In this study, we aimed to explore A3AR expression levels in psoriasis patients and its role in mediating the anti-inflammatory effect of piclidenoson in human keratinocyte cells. A3AR expression levels were evaluated in skin tissue and PBMCs derived from psoriasis patients and healthy subjects. Proliferation assay and the expression of signaling proteins were used to evaluate piclidenoson effect on human keratinocytes (HaCat). High A3AR expression levels were found in a skin biopsy and in PBMCs from psoriasis patients in comparison to healthy subjects. Piclidenoson inhibited the proliferation of HaCat cells through deregulation of the NF-κB signaling pathway, leading to a decrease in interleukin-17 and interleukin-23 expression levels. This effect was counteracted by the specific antagonist MRS 1523. A3AR overexpression in skin and PBMCs of psoriasis patients may be used as a target to inhibit pathological cell proliferation and the production of interleukin-17 and interleukin-23

Selective immunotargeting of diabetogenic CD4 T cells by genetically redirected T cells

The key role played by islet-reactive CD8 and CD4 T cells in type 1 diabetes calls for new immunotherapies that target pathogenic T cells in a selective manner. We previously demonstrated that genetically linking the signalling portion of CD3-ζ onto the C-terminus of β2-microglobulin and an autoantigenic peptide to its N-terminus converts MHC-I complexes into functional T-cell receptor-specific receptors. CD8 T cells expressing such receptors specifically killed diabetogenic CD8 T cells, blocked T-cell-induced diabetes in immunodeficient NOD.SCID mice and suppressed disease in wild-type NOD mice. Here we describe the immunotargeting of CD4 T cells by chimeric MHC-II receptors. To this end we chose the diabetogenic NOD CD4 T-cell clone BDC2.5, which recognizes the I-Ag7-bound 1040-31 mimotope. We assembled several constructs encoding I-Ag7 α- and β-chains, the latter carrying mim or hen egg lysozyme peptide as control, each supplemented with CD3-ζ intracellular portion, either with or without its transmembrane domain. Following mRNA co-transfection of reporter B3Z T cells and mouse CD8 and CD4 T cells, these constructs triggered robust activation upon I-Ag7 cross-linking. A BDC2.5 T-cell hybridoma activated B3Z transfectants expressing the mimotope, but not the control peptide, in both configurations. Potent two-way activation was also evident with transgenic BDC2.5 CD4 T cells, but peptide-specific activation required the CD3-ζ transmembrane domain. Chimeric MHC-II/CD3-ζ complexes therefore allow the selective immunotargeting of islet-reactive CD4 T cells, which take part in the pathogenesis of type 1 diabetes