Burkholderia cenocepacia O polysaccharide chain contributes to caspase-1-dependent IL-1 beta production in macrophages

Burkholderia cenocepacia infections in CF patients involve heightened inflammation, fatal sepsis, and high antibiotic resistance. Proinflammatory IL-1 beta secretion is important in airway inflammation and tissue damage. However, little is known about this pathway in macrophages upon B. cenocepacia infection. We report here that murine macrophages infected with B. cenocepacia K56-2 produce proinflammatory cytokine IL-1 beta in a TLR4 and caspase-1-mediated manner. We also determined that the OPS (O antigen) of B. cenocepacia LPS contributes to IL-1 beta production and pyroptotic cell death. Furthermore, we showed that the malfunction of the CFTR channel augmented IL-1 beta production upon B. cenocepacia infection of murine macrophages. Taken together, we identified eukaryotic and bacterial factors that contribute to inflammation during B. cenocepacia infection, which may aid in the design of novel approaches to control pulmonary inflammation. J. Leukoc. Biol. 89: 481-488; 2011.

Human figure segmentation using independent component analysis

In this paper, we present a Statistical Shape Model for Human Figure Segmentation in gait sequences. Point Distribution Models (PDM) generally use Principal Component analysis (PCA) to describe the main directions of variation in the training set. However, PCA assumes a number of restrictions on the data that do not always hold. In this work, we explore the potential of Independent Component Analysis (ICA) as an alternative shape decomposition to the PDM-based Human Figure Segmentation. The shape model obtained enables accurate estimation of human figures despite segmentation errors in the input silhouettes and has really good convergence qualities.

Electron-acoustic solitary waves in the presence of a suprathermal electron component

The nonlinear dynamics of electron-acoustic localized structures in a collisionless and unmagnetized plasma consisting of “cool” inertial electrons, “hot” electrons having a kappa distribution, and stationary ions is studied. The inertialess hot electron distribution thus has a long-tailed suprathermal (non-Maxwellian) form. A dispersion relation is derived for linear electron-acoustic waves. They show a strong dependence of the charge screening mechanism on excess suprathermality (through ?). A nonlinear pseudopotential technique is employed to investigate the occurrence of stationary-profile solitary waves, focusing on how their characteristics depend on the spectral index ?, and the hot-to-cool electron temperature and density ratios. Only negative polarity solitary waves are found to exist, in a parameter region which becomes narrower as deviation from the Maxwellian (suprathermality) increases, while the soliton amplitude at fixed soliton speed increases. However, for a constant value of the true Mach number, the amplitude decreases for decreasing ?.

Cutting Edge: Suppression of GM-CSF Expression in Murine and Human T Cells by IL-27

GM-CSF is a potent proinflammatory cytokine that plays a pathogenic role in the CNS inflammatory disease experimental autoimmune encephalomyelitis. As IL-27 alleviates experimental autoimmune encephalomyelitis, we hypothesized that IL-27 suppresses GM-CSF expression by T cells. We found that IL-27 suppressed GM-CSF expression in CD4+ and CD8+ T cells in splenocyte and purified T cell cultures. IL-27 suppressed GM-CSF in Th1, but not Th17, cells. IL-27 also suppressed GM-CSF expression by human T cells in nonpolarized and Th1- but not Th17-polarized PBMC cultures. In vivo, IL-27p28 deficiency resulted in increased GM-CSF expression by CNS-infiltrating T cells during Toxoplasma gondii infection. Although in vitro suppression of GM-CSF by IL-27 was independent of IL-2 suppression, IL-10 upregulation, or SOCS3 signaling, we observed that IL-27-driven suppression of GM-CSF was STAT1 dependent. Our findings demonstrate that IL-27 is a robust negative regulator of GM-CSF expression in T cells, which likely inhibits T cell pathogenicity in CNS inflammation.

Improvising (Il)legality: Justice and the Irish Diaspora, NYC, 1930-32

The Seabury Commission, 1930-32, probed allegations of corruption made against, amongst others, the Irish-American Mayor of New York City, James J. ‘Jimmy’ Walker, and the Irish-dominated Tammany Hall, the Democratic political machine that had supported Walker. Taking the Seabury inquiry as its focus, this article explores these allegations from the perspective of Critical Studies in Improvisation (C.S.I.) fused with postcolonial critique. Improvisation, in accordance with C.S.I. principles, is not a lawless or extempore event; it is, instead, lawful, or full of law. The laws of improvisation may appear impenetrable to those unfamiliar with the practice. However, when read through a hibernocentric postcolonial perspective, their meaning and form become more understandable. As will be argued in this article, diasporic communities are inherently improvisatory; that is, they utilise improvisational techniques to help adapt and respond to new situations and social contexts. To be queried is whether the law and politics practiced by Tammany and Walker, taken together, constituted a markedly Irish approach to justice, one that entailed not scripted or planned illegality, as was alleged by Judge Seabury, but improvisations on Anglo-Protestant law as a response to the displacement of and discrimination against the Irish Diaspora in early twentieth century America.

Cellular senescence induced by aberrant MAD2 levels impacts on paclitaxel responsiveness in vitro

BACKGROUND: The mitotic arrest deficiency protein 2 (MAD2) is a key component of the mitotic spindle assembly checkpoint, monitoring accurate chromosomal alignment at the metaphase plate before mitosis. MAD2 also has a function in cellular senescence and in a cell’s response to microtubule inhibitory (MI) chemotherapy exemplified by paclitaxel.
METHODS: Using an siRNA approach, the impact of MAD2 down-regulation on cellular senescence and paclitaxel responsiveness was investigated. The endpoints of senescence, cell viability, migration, cytokine expression, cell cycle analysis and anaphase bridge scoring were carried out using standard approaches.
RESULTS: We show that MAD2 down-regulation induces premature senescence in the MCF7 breast epithelial cancer cell line. These MAD2-depleted (MAD2k) cells are also significantly replicative incompetent but retain viability. Moreover, they show significantly higher levels of anaphase bridges and polyploidy compared to controls. In addition, these cells secrete higher levels of IL-6 and IL-8
representing key components of the senescence-associated secretory phenotype (SASP) with the ability to impact on neighbouring cells. In support of this, MAD2kcells show enhanced migratory ability. At 72 h after paclitaxel, MAD2kcells show a significant further induction of senescence compared with paclitaxel naive controls. In addition, there are significantly more viable cells in the MAD2k MCF7 cell line after paclitaxel reflecting the observed increase in senescence.
CONCLUSION: Considering that paclitaxel targets actively dividing cells, these senescent cells will evade cytotoxic kill. In conclusion, compromised MAD2 levels induce a population of senescent cells resistant to paclitaxel.