A Functional Proteomic Method for Biomarker Discovery

The sequencing of the human genome holds out the hope for personalized medicine, but it is clear that analysis of DNA or RNA content alone is not sufficient to understand most disease processes. Proteomic strategies that allow unbiased identification of proteins and their post-transcriptional and -translation modifications are an essential complement to genomic strategies. However, the enormity of the proteome and limitations in proteomic methods make it difficult to determine the targets that are particularly relevant to human disease. Methods are therefore needed that allow rational identification of targets based on function and relevance to disease. Screening methodologies such as phage display, SELEX, and small-molecule combinatorial chemistry have been widely used to discover specific ligands for cells or tissues of interest, such as tumors. Those ligands can be used in turn as affinity probes to identify their cognate molecular targets when they are not known in advance. Here we report an easy, robust and generally applicable approach in which phage particles bearing cell- or tissue-specific peptides serve directly as the affinity probes for their molecular targets. For proof of principle, the method successfully identified molecular binding partners, three of them novel, for 15 peptides specific for pancreatic cancer

FHA-Mediated Cell-Substrate and Cell-Cell Adhesions Are Critical for Bordetella pertussis Biofilm Formation on Abiotic Surfaces and in the Mouse Nose and the Trachea

Bordetella spp. form biofilms in the mouse nasopharynx, thereby providing a potential mechanism for establishing chronic infections in humans and animals. Filamentous hemagglutinin (FHA) is a major virulence factor of B. pertussis, the causative agent of the highly transmissible and infectious disease, pertussis. In this study, we dissected the role of FHA in the distinct biofilm developmental stages of B. pertussis on abiotic substrates and in the respiratory tract by employing a murine model of respiratory biofilms. Our results show that the lack of FHA reduced attachment and decreased accumulation of biofilm biomass on artificial surfaces. FHA contributes to biofilm development by promoting the formation of microcolonies. Absence of FHA from B. pertussis or antibody-mediated blockade of surface-associated FHA impaired the attachment of bacteria to the biofilm community. Exogenous addition of FHA resulted in a dose-dependent inhibitory effect on bacterial association with the biofilms. Furthermore, we show that FHA is important for the structural integrity of biofilms formed on the mouse nose and trachea. Together, these results strongly support the hypothesis that FHA promotes the formation and maintenance of biofilms by mediating cell-substrate and inter-bacterial adhesions. These discoveries highlight FHA as a key factor in establishing structured biofilm communities in the respiratory tract

Systems microscopy approaches to understand cancer cell migration and metastasis

Cell migration is essential in a number of processes, including wound healing, angiogenesis and cancer metastasis. Especially, invasion of cancer cells in the surrounding tissue is a crucial step that requires increased cell motility. Cell migration is a well-orchestrated process that involves the continuous formation and disassembly of matrix adhesions. Those structural anchor points interact with the extra-cellular matrix and also participate in adhesion-dependent signalling. Although these processes are essential for cancer metastasis, little is known about the molecular mechanisms that regulate adhesion dynamics during tumour cell migration. In this review, we provide an overview of recent advanced imaging strategies together with quantitative image analysis that can be implemented to understand the dynamics of matrix adhesions and its molecular components in relation to tumour cell migration. This dynamic cell imaging together with multiparametric image analysis will help in understanding the molecular mechanisms that define cancer cell migration

A qualitative investigation of support workers’ experiences of the impact of the COVID-19 pandemic on Dutch migrant families who have children with intellectual disabilities

Background The COVID-19 pandemic significantly affected families who have children with intellectual disabilities (ID). Our aim was to explore the pandemic’s impact on Dutch migrant families who have children with ID, by interviewing these families’ support workers. Method A descriptive qualitative methodology was employed, which resulted in semi-structured telephone interviews with 34 support workers. We selected interview transcripts that pertained to 27 Dutch migrant families who have children with ID and identified themes and subthemes using thematic analysis. Results Two main themes related to the pandemic emerged: (1) Work of support workers during the COVID-19 pandemic and (2) Impact of the COVID-19 pandemic upon migrant families who have children with ID. Conclusion The present study demonstrates that support workers particularly struggled to stay in touch with migrant families who have children with ID during the COVID-19 pandemic. Therefore, support workers should tailor their support to the needs of migrant families

Ventures in public value management : Introduction to the symposium

This essay reviews the development of public value management, tracing its rise from relative obscurity in the 1990s to the global attention it receives today. We also introduce the accompanying essays in this symposium which aim to spur further development in the years to come. We review the main tenets of public value management and highlight the key debates in the literature, discussing the mandate of public managers vis-a-vis politicians, the mobilization of ‘the public’, the framing of strategic challenges and the distinctiveness of value creation in the public domain. The five accompanying essays deal with these debates, but also break new ground by addressing fresh questions