Putting "space" on the agenda of sociocultural research in education

The global rescaling of the world, culture, and education has influenced how people experience their situationality, meaning-making, and learning in relation to the Other. This article explores the implications of spatial analysis for rethinking education in new conditions of cultural complexity. The experience of living and learning with difference is conceptualized as an open journey in which the very act of movement across spatial boundaries unlocks the fixity of meanings and identities and, hence, problematizes the spatial logic of bounded learning places. Explicating the tension between fixity and mobility, boundedness and flows, this article deploys the concepts of cultural-semiotic space, scale, and boundary to theorize locations of learning and meaning-making in new times. <br /

A Yersinia Effector with Enhanced Inhibitory Activity on the NF-κB Pathway Activates the NLRP3/ASC/Caspase-1 Inflammasome in Macrophages

A type III secretion system (T3SS) in pathogenic Yersinia species functions to translocate Yop effectors, which modulate cytokine production and regulate cell death in macrophages. Distinct pathways of T3SS-dependent cell death and caspase-1 activation occur in Yersinia-infected macrophages. One pathway of cell death and caspase-1 activation in macrophages requires the effector YopJ. YopJ is an acetyltransferase that inactivates MAPK kinases and IKKβ to cause TLR4-dependent apoptosis in naïve macrophages. A YopJ isoform in Y. pestis KIM (YopJKIM) has two amino acid substitutions, F177L and K206E, not present in YopJ proteins of Y. pseudotuberculosis and Y. pestis CO92. As compared to other YopJ isoforms, YopJKIM causes increased apoptosis, caspase-1 activation, and secretion of IL-1β in Yersinia-infected macrophages. The molecular basis for increased apoptosis and activation of caspase-1 by YopJKIM in Yersinia-infected macrophages was studied. Site directed mutagenesis showed that the F177L and K206E substitutions in YopJKIM were important for enhanced apoptosis, caspase-1 activation, and IL-1β secretion. As compared to YopJCO92, YopJKIM displayed an enhanced capacity to inhibit phosphorylation of IκB-α in macrophages and to bind IKKβ in vitro. YopJKIM also showed a moderately increased ability to inhibit phosphorylation of MAPKs. Increased caspase-1 cleavage and IL-1β secretion occurred in IKKβ-deficient macrophages infected with Y. pestis expressing YopJCO92, confirming that the NF-κB pathway can negatively regulate inflammasome activation. K+ efflux, NLRP3 and ASC were important for secretion of IL-1β in response to Y. pestis KIM infection as shown using macrophages lacking inflammasome components or by the addition of exogenous KCl. These data show that caspase-1 is activated in naïve macrophages in response to infection with a pathogen that inhibits IKKβ and MAPK kinases and induces TLR4-dependent apoptosis. This pro-inflammatory form of apoptosis may represent an early innate immune response to highly virulent pathogens such as Y. pestis KIM that have evolved an enhanced ability to inhibit host signaling pathways

Environment: Contributions of Design and Education to the Sustainment of Planet Earth

Any book that aims to deal with issues of sustainable futures will necessarily have a significant focus on environmental sustainability. Historically, concerns over sustainable futures were predominantly focused on the environment, with references going back as far as, for example, the 7th century when legislation was introduced to protect birds in the Farne Islands off the north east coast of England. More recently there has been recognition that sustainable futures depend on complex sets of relationships

Individual approach to choosing an appropriate regimen of adjuvant hormone therapy in patients with early-stage breast cancer

Adjuvant hormone therapy is considered the gold standard of therapy for hormone receptor-positive operable breast cancer. The approach to adjuvant hormone therapy in premenopausal patients has changed significantly in recent years. This change was caused by clinical trials, which have confirmed the advantage of adding ovarian suppression to tamoxifen or aromatase inhibitors monotherapy. Individual approach to choosing an appropriate regimen of adjuvant hormone therapy in premenopausal patients with breast cancer should be based on the assessment of risks for relapse, expected effectiveness of treatment and evaluation of drug safety