Integrin-mediated Cell Attachment Induces a PAK4-dependent Feedback Loop Regulating Cell Adhesion through Modified Integrin αvβ5 Clustering and Turnover

This article presents a novel mechanism deployed by cells to tune cell adhesion levels through the autoinhibitory regulation of integrin adhesion involving the activation of PAK4

Unravelling the determinants of carpool behaviour in Flanders, Belgium: Integration of qualitative and quantitative research

peer reviewedThe goal of this study is to identify those factors that trigger carpoolers to share their rides and the barriers that restrain non-carpoolers from doing so. To this end, four focus group sessions were organized. In addition, information from the 2009-2010 Flemish household travel survey was analysed. From the focus group discussions, it can be concluded that the concept of carpooling is generally well known, but that the media attention and stimuli for the topic seem to have faded away over time. The main motivations to carpool are the social aspect, the financial benefit or a combination of both. The quantitative analysis underlined for the difference between the distinct types of employees. Furthermore, the finding that the home-work distance increases the likelihood to carpool emphasizes the importance of the financial benefits of carpooling. Financial stimuli are thought to have the most potential to increase the share of carpooling in the modal split

Scientific Representations as Limiting Cases

In this essay, I shall show that the so-called inferential (Suárez 2003 and 2004) and interpretational (Contessa 2007) accounts of scientific representation are respectively unsatisfactory and too weak to account for scientific representation (pars destruens). Along the way, I shall also argue that the pragmatic similarity (Giere 2004 and Giere 2010) and the partial isomorphism (da Costa and French 2003 and French 2003) accounts are unable to single out scientific representation. In the pars construens I spell out a limiting case account which has explanatory surplus vis à vis the approaches which I have previously reviewed. My account offers an adequate treatment of scientific representation, or so I shall try to argue. Central to my account is the notion of a pragmatic limiting case, which will be characterized in due course

Indirect cholinergic activation slows down pancreatic cancer growth and tumor-associated inflammation

Background!#!Nerve-cancer interactions are increasingly recognized to be of paramount importance for the emergence and progression of pancreatic cancer (PCa). Here, we investigated the role of indirect cholinergic activation on PCa progression through inhibition of acetylcholinesterase (AChE) via clinically available AChE-inhibitors, i.e. physostigmine and pyridostigmine.!##!Methods!#!We applied immunohistochemistry, immunoblotting, MTT-viability, invasion, flow-cytometric-cell-cycle-assays, phospho-kinase arrays, multiplex ELISA and xenografted mice to assess the impact of AChE inhibition on PCa cell growth and invasiveness, and tumor-associated inflammation. Survival analyses were performed in a novel genetically-induced, surgically-resectable mouse model of PCa under adjuvant treatment with gemcitabine+/-physostigmine/pyridostigmine (n = 30 mice). Human PCa specimens (n = 39) were analyzed for the impact of cancer AChE expression on tumor stage and survival.!##!Results!#!We discovered a strong expression of AChE in cancer cells of human PCa specimens. Inhibition of this cancer-cell-intrinsic AChE via pyridostigmine and physostigmine, or administration of acetylcholine (ACh), diminished PCa cell viability and invasion in vitro and in vivo via suppression of pERK signaling, and reduced tumor-associated macrophage (TAM) infiltration and serum pro-inflammatory cytokine levels. In the novel genetically-induced, surgically-resectable PCa mouse model, adjuvant co-therapy with AChE blockers had no impact on survival. Accordingly, survival of resected PCa patients did not differ based on tumor AChE expression levels. Patients with higher-stage PCa also exhibited loss of the ACh-synthesizing enzyme, choline-acetyltransferase (ChAT), in their nerves.!##!Conclusion!#!For future clinical trials of PCa, direct cholinergic stimulation of the muscarinic signaling, rather than indirect activation via AChE blockade, may be a more effective strategy