A Novel Role for CD55 in Granulocyte Homeostasis and Anti-Bacterial Host Defense

Background: In addition to its complement-regulating activity, CD55 is a ligand of the adhesion class G protein-coupled receptor CD97; however, the relevance of this interaction has remained elusive. We previously showed that mice lacking a functional CD97 gene have increased numbers of granulocytes. Methodology/Results: Here,wedemonstratethatCD55-deficientmicedisplay a comparable phenotype with about two-fold more circulating granulocytes in the blood stream, the marginated pool, and the spleen. This granulocytosis was independent of increased complement activity. Augmented numbers of Gr-1-positive cells in cell cycle in the bone marrow indicated a higher granulopoietic activity in mice lacking either CD55 or CD97. Concomitant with the increase in blood granulocyte numbers, Cd55-/mice challenged with the respiratory pathogen Streptococcus pneumoniae developed less bacteremia and died later after infection. Conclusions: Collectively, these data suggest that complement-independent interaction of CD55 with CD97 is functionall

Tactical urbanism as a means of testing relational processes in space: A complex systems perspective

Too often, master planning strategies have failed to produce spaces responding to the social, cultural, and economic needs of their inhabitants. Accordingly, many planners have turned to relational strategies to redefine their practices. These tend toward methodologies that explore relational forces preceding design interventions rather than unfolding by means of design interventions. This article considers an alternative mode of understanding relational processes: one that considers tactical urban strategies theorized through the lens of complexity theory. This article argues that tactical approaches harness relational junctures in situ, effectively exploring relational configurations of cohesive urban environments. A design competition entry provides an illustrative example of this approach: one that channels and choreographs relational urban processes

Cancer Genomics Identifies Regulatory Gene Networks Associated with the Transition from Dysplasia to Advanced Lung Adenocarcinomas Induced by c-Raf-1

Background: Lung cancer is a leading cause of cancer morbidity. To improve an understanding of molecular causes of disease a transgenic mouse model was investigated where targeted expression of the serine threonine kinase c-Raf to respiratory epithelium induced initialy dysplasia and subsequently adenocarcinomas. This enables dissection of genetic events associated with precancerous and cancerous lesions. Methodology/Principal Findings: By laser microdissection cancer cell populations were harvested and subjected to whole genome expression analyses. Overall 473 and 541 genes were significantly regulated, when cancer versus transgenic and non-transgenic cells were compared, giving rise to three distinct and one common regulatory gene network. At advanced stages of tumor growth predominately repression of gene expression was observed, but genes previously shown to be upregulated in dysplasia were also up-regulated in solid tumors. Regulation of developmental programs as well as epithelial mesenchymal and mesenchymal endothelial transition was a hall mark of adenocarcinomas. Additionaly, genes coding for cell adhesion, i.e. the integrins and the tight and gap junction proteins were repressed, whereas ligands for receptor tyrosine kinase such as epi- and amphiregulin were up-regulated. Notably, Vegfr- 2 and its ligand Vegfd, as well as Notch and Wnt signalling cascades were regulated as were glycosylases that influence cellular recognition. Other regulated signalling molecules included guanine exchange factors that play a role in an activation of the MAP kinases while several tumor suppressors i.e. Mcc, Hey1, Fat3, Armcx1 and Reck were significantly repressed. Finally, probable molecular switches forcing dysplastic cells into malignantly transformed cells could be identified. Conclusions/Significance: This study provides insight into molecular pertubations allowing dysplasia to progress further to adenocarcinoma induced by exaggerted c-Raf kinase activity

Radiotherapeutic alternatives for previously irradiated recurrent gliomas

Re-irradiation for recurrent gliomas has been discussed controversially in the past. This was mainly due to only marginal palliation while being associated with a high risk for side effects using conventional radiotherapy