Civil-military relations in peacebuilding

Civil-military relations are vital to the coherence and effectiveness of post-conflict peacebuilding, but have often been problematic. This article argues that civil-military issues vary systematically in relation to the particular civil and military actors in peacebuilding, and that the coercive content of the external military's mission creates special challenges in each of these sets of relationships. Given the significance of the military footprint, the article presents trade-offs for policymakers intending to use military forces to make peace

Elections in Iraq: Managing Expectations; Strategic Insights, V. 6, issue 2 (February 2005 )

This article appeared in Strategic Insights, v.6, issue 2 (February 2005 )Approved for public release; distribution is unlimited

Introduction to the Special issue on Interim Governments; Strategic Insights, v. 5, issue 1 (January 2006)

This article appeared in Strategic Insights, v.5, issue 1 (January 2006)Approved for public release; distribution is unlimited

Conference Report: Interim Governments: Institutional Bridges to Peace and Democracy?; Strategic Insights, v. 5, issue 1 (January 2006)

This article appeared in Strategic Insights, v.5, issue 1 (January 2006)Approved for public release; distribution is unlimited

EMT/autophagy crosstalk: role of the aberrant expression of the mesenchymal FGFR2c isoform

In epithelial context the aberrant expression of the mesenchymal FGFR2c isoform in epithelial cells induces impaired differentiation inhibition of autophagy as well as the induction of the epithelial-mesenchymal transition (EMT). Considering the widely proposed negative loop linking autophagy and EMT in the early steps of carcinogenesis, in this thesis work we investigated the possible involvement of FGFR2c aberrant expression and signalling in orchestrating this crosstalk. In human keratinocytes context, biochemical, molecular, quantitative immunofluorescence analysis and in vitro invasion assays, coupled to the use of specific substrate inhibitors and transient or stable silencing approaches, showed that AKT/MTOR and PKCε are the two hub signalling pathways, downstream FGFR2c, intersecting with each other in the control of both the inhibition of autophagy and the induction of EMT and invasive behavior. These results indicate that the out of context expression of FGFR2c, could represent a key upstream event responsible for the establishment of a negative interplay between autophagy and EMT. FGFR2 isoform switch is recognized as one of the oncogenic events occurring during pancreatic carcinogenesis, whose contribution in EMT induction and cell invasion, as well as in the dysregulation of autophagy still appears controversial. In fact, pancreatic ductal adenocarcinoma (PDAC) is a treatment-resistant malignancy characterized by a high malignant phenotype including acquired EMT signature and deregulated autophagy. Since we have previously described that the aberrant expression of the mesenchymal FGFR2c and the triggering of the downstream PKC signaling are involved in epidermal carcinogenesis, the aim of this work has been to assess the contribution of these oncogenic events also in the pancreatic context. Biochemical, molecular and immunofluorescence approaches showed that FGFR2c expression impacts on PDAC cell responsiveness to FGF2 in terms of intracellular signaling activation, upregulation of EMT-related transcription factors and modulation of epithelial and mesenchymal markers compatible with the pathological EMT. Moreover, shut-off via specific 7 protein depletion of PKC signaling, activated by high expression of FGFR2c resulted in a reversion of EMT profile, as well as in a recovery of the autophagic process. The detailed biochemical analysis of the intracellular signaling indicated that PKCε, bypassing AKT and directly converging on ERK1/2, could be a signaling molecule downstream FGFR2c whose inhibition could be considered as possible effective therapeutic approach in counteracting aggressive phenotype in cancer

Cebrowski Institute Brown Bag Luncheon

Karen Guttieri and Chris Gunderson participated in the DARPA workshop on Strategic Collaboration in SSTR/HADR in Arlington, VA and presented the NPS inventory of strategic capacity. The workshop used a team approach to develop solutions to Disaster Relief with specific concentration in the themes of semantic glue, ad hoc networking, mobile computing, human network performance, mensuration, and system level issues

The aberrant expression in epithelial cells of the mesenchymal isoform of FGFR2 controls the negative crosstalk between EMT and autophagy

Signalling of the epithelial splicing variant of fibroblast growth factor receptor 2 (FGFR2b) triggers both differentiation and autophagy, while the aberrant expression of the mesenchymal FGFR2c isoform in epithelial cells induces impaired differentiation, inhibition of autophagy as well as the induction of the epithelial-mesenchymal transition (EMT). In light of the widely proposed negative loop linking autophagy and EMT in the early steps of carcinogenesis, here we investigated the possible involvement of FGFR2c aberrant expression and signalling in orchestrating this crosstalk in human keratinocytes. Biochemical, molecular, quantitative immunofluorescence analysis and in vitro invasion assays, coupled to the use of specific substrate inhibitors and transient or stable silencing approaches, showed that AKT/MTOR and PKCε are the two hub signalling pathways, downstream FGFR2c, intersecting with each other in the control of both the inhibition of autophagy and the induction of EMT and invasive behaviour. These results indicate that the expression of FGFR2c, possibly resulting from FGFR2 isoform switch, could represent a key upstream event responsible for the establishment of a negative interplay between autophagy and EMT, which contributes to the assessment of a pathological oncogenic profile in epithelial cells

Ire1 alpha/xbp1 axis sustains primary effusion lymphoma cell survival by promoting cytokine release and stat3 activation

Primary Effusion Lymphoma (PEL) is a highly aggressive B cell lymphoma associated with Kaposi’s Sarcoma-associated Herpesvirus (KSHV). It is characterized by a high level of basal Endoplasmic Reticulum (ER) stress, Unfolded Protein Response (UPR) activation and constitutive phosphorylation of oncogenic pathways such as the Signal Transducer and activator of Transcription (STAT3). In this study, we found that the inositol requiring kinase (IRE) 1alpha/X-box binding protein (XBP1) axis of UPR plays a key role in the survival of PEL cells, while double stranded RNA-activated protein kinase-like ER kinase (PERK) and activating transcription factor (ATF) 6 slightly influence it, in correlation with the capacity of the IRE1alpha/XBP1 axis to induce the release of interleukin (IL)-6, IL-10 and Vascular-Endothelial Growth Factor (VEGF). Moreover, we found that IRE1alpha/XBP1 inhibition reduced STAT3 Tyr705 phosphorylation and induced a pro-survival autophagy in PEL cells. In conclusion, this study suggests that targeting the IRE1alpha/XBP1 axis represents a promising strategy against PEL cells and that the cytotoxic effect of this treatment may be potentiated by autophagy inhibition

Global Public Policy Academic Group Holds Global Challenges Program in Geneva

Faculty Showcase Archive ArticleApproved for public release; distribution is unlimited