Computed tomography features of basal ganglia and periventricular calcifications in childhood

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Absent in Melanoma 2 (AIM2) is an important mediator of interferon-dependent and -independent HLA-DRA and HLA-DRB gene expression in colorectal cancers

Absent in Melanoma 2 (AIM2) is a member of the HIN-200 family of hematopoietic, IFN-inducible, nuclear proteins, associated with both, infection defense and tumor pathology. Recently, AIM2 was found to act as a DNA sensor in innate immunity. In addition, we and others have previously demonstrated a high frequency of AIM2-alterations in microsatellite unstable (MSI-H) tumors. To further elucidate AIM2 function in colorectal tumors, we here addressed AIM2-responsive target genes by microarray based gene expression profiling of 22 244 human genes. A total of 111 transcripts were significantly upregulated, whereas 80 transcripts turned out to be significantly downregulated in HCT116 cells, constitutively expressing AIM2, compared with AIM2-negative cells. Among the upregulated genes that were validated by quantitative PCR and western blotting we recognized several interferon-stimulated genes (ISGs: IFIT1, IFIT2, IFIT3, IFI6, IRF7, ISG15, HLA-DRA, HLA-DRB, TLR3 and CIITA), as well as genes involved in intercellular adhesion and matrix remodeling. Expression of ISGs correlated with expression of AIM2 in 10 different IFN-γ treated colorectal cancer cell lines. Moreover, small interfering RNA-mediated knock-down of AIM2 resulted in reduced expression of HLA-DRA, HLA-DRB and CIITA in IFN-γ-treated cells. IFN-γ independent induction of HLA-DR genes and their encoded proteins was also demonstrated upon doxycyclin-regulated transient induction of AIM2. Luciferase reporter assays revealed induction of the HLA-DR promoter upon AIM2 transfection in different cell lines. STAT-signaling was not involved in IFN-γ independent induction of ISGs, arguing against participation of cytokines released in an autostimulating manner. Our data indicate that AIM2 mediates both IFN-γ dependent and independent induction of several ISGs, including genes encoding the major histocompatibility complex (MHC) class II antigens HLA-DR-α and -β. This suggests a novel role of the IFN/AIM2/ISG cascade likewise in cancer cells

Old wine in new bottles: Exploring pragmatism as a philosophical framework for the discipline of coaching

The practice and industry of organizational coaching are now well established, but how it is understood theoretically continues to lag behind. In this paper we analyze possible reasons for this state of affairs and argue that the development of coaching as an academic discipline will benefit from adopting philosophical pragmatism as an overarching theoretical framework. This move will enable coaching academics to utilize the contributions to knowledge that different paradigms generate. Positioning pragmatism as a theory of action we argue that organizational coaching is by default a pragmatic enterprise and provide three examples of the considerable benefits to be gained by conceptualizing it this way. (1) Drawing from the pragmatists’ ideas, particularly those of John Dewey, we demonstrate how the theoretical understanding of organizational coaching can be enhanced by considering its nature as a joint inquiry. (2) Pragmatism suggests development as an ultimate purpose for organizational coaching which also helps to resolve fundamental conceptual debates. (3) In light of the complexity and diversity involved in the way that organizational coaching is practiced, pragmatism offers coaches a useful framework for developing the flexibility required for navigating the multiplicity of influences on their practice