Retrieving and recontextualising VET theory

To what extent can we speak of theory specific to vocational education and training (VET) and what is its relevance today? This Special Issue 19 of bwp@ aims to (re)ignite academic discourse on VET theory, retrieving earlier theorisation specific to this field, mainly from Germany, Austria, and Switzerland (the DACH countries) and connecting it both with international perspectives and contemporary debates. We invite papers in English or German that engage with these debates. From an international perspective, the DACH countries are extraordinary both in their proposition of theories of VET sui generis and especially in their influence on the field of policy and practice. By contrast, for example in English-speaking countries, influential theories that address the question of vocational study, whilst drawing extensively on philosophical and social science concepts, developed largely in opposition to policy and practices that positioned vocational learning as an inferior pathway and narrowed its educational scope. The dual apprenticeship model has been widely imitated internationally but without regard to the social partnerships, labour markets and education workforce developed in Germany, and the theories that shaped this system are neither translated nor widely discussed in other languages. While there are several approaches to VET theory, the core of all these approaches is a framework of normative goals of education, a characterisation of how these goals can be reached through vocational education in particular and the formulation of (education) policy implications that are necessary for successful implementation. For example, Kerschensteiner (1901, 1966/1904) in his emphasis on civic virtues as a central aim of education, drew attention to the possibility of attaining such virtues through work, but acknowledged the necessity of a foundation in general education. In contrast, post-war critical approaches, which regularly draw on critical theory (see Habermas 1968; Horkheimer & Adorno 1947), and can be dated to the 1960s and 1970s, identify autonomy and emancipation as central objectives of education (e.g. Lempert 1971; Blankertz 1974, 1979, 1982). The main challenge of VET theory was to explain how these goals also can be reached through vocational education. Blankertz’s answer lay in emphasizing the role of the VET school in widening and deepening knowledge associated with the workspace. The value of these approaches for contemporary VET is dependent on their adaptation to contemporary problems that VET and society are experiencing: migration and integration; climate change and resource consumption, digitisation and globalisation. The tertiarisation of both the economy and of education, as the service sector employs a greater proportion of the population and a growing number of young people enter higher education, even in Germany, also calls into question the relevance of established VET theories. As the structures and forms of organisation that have sustained VET since the 1970s have given way to new social formations and new forms of precarity, the relevance of theories developed during the long period of post-war growth is called into question. Correspondingly, whether a critical standpoint can still be clearly located after the “fall of metaphysics” (Adorno 1998/1965) has also been deemed as questionable (cf. Schäfer 2005). Furthermore, a succession of de-centring approaches including post-structuralist, postmodernist and post-anthropocentric paradigms has suggested the erosion of earlier ‘grand narratives’, the supersession of the ‘enlightenment project’ and even questioned the progressive potential of human labour that explicitly VET theories tend to take for granted. Call for Papers bwp@ Spezial 19 2 Against this background, the bwp@ Special invites contributions that address both VET theory and its application to contemporary issues. The aim is to stimulate a discussion on the continuing significance of VET theory. The aim is to provide space for ideas on how the discipline and its subject could position itself, both nationally and beyond national borders, in its normative-theoretical contours and/or in relation to VET policy and VET practice

A molecularly characterized preclinical platform of subcutaneous renal cell carcinoma (RCC) patient-derived xenograft models to evaluate novel treatment strategies

Renal cell carcinoma (RCC) is a kidney cancer with an onset mainly during the sixth or seventh decade of the patient’s life. Patients with advanced, metastasized RCC have a poor prognosis. The majority of patients develop treatment resistance towards Standard of Care (SoC) drugs within months. Tyrosine kinase inhibitors (TKIs) are the backbone of first-line therapy and have been partnered with an immune checkpoint inhibitor (ICI) recently. Despite the most recent progress, the development of novel therapies targeting acquired TKI resistance mechanisms in advanced and metastatic RCC remains a high medical need. Preclinical models with high translational relevance can significantly support the development of novel personalized therapies. It has been demonstrated that patient-derived xenograft (PDX) models represent an essential tool for the preclinical evaluation of novel targeted therapies and their combinations. In the present project, we established and molecularly characterized a comprehensive panel of subcutaneous RCC PDX models with well-conserved molecular and pathological features over multiple passages. Drug screening towards four SoC drugs targeting the vascular endothelial growth factor (VEGF) and PI3K/mTOR pathway revealed individual and heterogeneous response profiles in those models, very similar to observations in patients. As unique features, our cohort includes PDX models from metastatic disease and multi-tumor regions from one patient, allowing extended studies on intra-tumor heterogeneity (ITH). The PDX models are further used as basis for developing corresponding in vitro cell culture models enabling advanced high-throughput drug screening in a personalized context. PDX models were subjected to next-generation sequencing (NGS). Characterization of cancer-relevant features including driver mutations or cellular processes was performed using mutational and gene expression data in order to identify potential biomarker or treatment targets in RCC. In summary, we report a newly established and molecularly characterized panel of RCC PDX models with high relevance for translational preclinical research

The invasome of Salmonella Dublin as revealed by whole genome sequencing

Background Salmonella enterica serovar Dublin is a zoonotic infection that can be transmitted from cattle to humans through consumption of contaminated milk and milk products. Outbreaks of human infections by S. Dublin have been reported in several countries including high-income countries. A high proportion of S. Dublin cases in humans are associated with invasive disease and systemic illness. The genetic basis of virulence in S. Dublin is not well characterized. Methods Whole genome sequencing was applied to a set of clinical invasive and non-invasive S. Dublin isolates from different countries in order to characterize the putative genetic determinants involved in the virulence and invasiveness of S. Dublin in humans. Results We identified several virulence factors that form the bacterial invasome and may contribute to increasing bacterial virulence and pathogenicity including mainly Gifsy-2 prophage, two different type 6 secretion systems (T6SSs) harbored by Salmonella pathogenicity islands; SPI-6 and SPI-19 respectively and virulence genes; ggt and PagN. Although Vi antigen and the virulence plasmid have been reported previously to contribute to the virulence of S. Dublin we did not detect them in all invasive isolates indicating that they are not the main virulence determinants in S. Dublin. Conclusion Several virulence factors within the genome of S. Dublin might contribute to the ability of S. Dublin to invade humans’ blood but there were no genomic markers that differentiate invasive from non-invasive isolates suggesting that host immune response play a crucial role in the clinical outcome of S. Dublin infection

Glutathione Provides a Source of Cysteine Essential for Intracellular Multiplication of Francisella tularensis

Francisella tularensis is a highly infectious bacterium causing the zoonotic disease tularemia. Its ability to multiply and survive in macrophages is critical for its virulence. By screening a bank of HimarFT transposon mutants of the F. tularensis live vaccine strain (LVS) to isolate intracellular growth-deficient mutants, we selected one mutant in a gene encoding a putative γ-glutamyl transpeptidase (GGT). This gene (FTL_0766) was hence designated ggt. The mutant strain showed impaired intracellular multiplication and was strongly attenuated for virulence in mice. Here we present evidence that the GGT activity of F. tularensis allows utilization of glutathione (GSH, γ-glutamyl-cysteinyl-glycine) and γ-glutamyl-cysteine dipeptide as cysteine sources to ensure intracellular growth. This is the first demonstration of the essential role of a nutrient acquisition system in the intracellular multiplication of F. tularensis. GSH is the most abundant source of cysteine in the host cytosol. Thus, the capacity this intracellular bacterial pathogen has evolved to utilize the available GSH, as a source of cysteine in the host cytosol, constitutes a paradigm of bacteria–host adaptation

Effects of Helicobacter suis γ-glutamyl transpeptidase on lymphocytes: modulation by glutamine and glutathione supplementation and outer membrane vesicles as a putative delivery route of the enzyme

Helicobacter (H.) suis colonizes the stomach of the majority of pigs as well as a minority of humans worldwide. Infection causes chronic inflammation in the stomach of the host, however without an effective clearance of the bacteria. Currently, no information is available about possible mechanisms H. suis utilizes to interfere with the host immune response. This study describes the effect on various lymphocytes of the γ-glutamyl transpeptidase (GGT) from H. suis. Compared to whole cell lysate from wild-type H. suis, lysate from a H. suis ggt mutant strain showed a decrease of the capacity to inhibit Jurkat T cell proliferation. Incubation of Jurkat T cells with recombinantly expressed H. suis GGT resulted in an impaired proliferation, and cell death was shown to be involved. A similar but more pronounced inhibitory effect was also seen on primary murine CD4+ T cells, CD8+ T cells, and CD19+ B cells. Supplementation with known GGT substrates was able to modulate the observed effects. Glutamine restored normal proliferation of the cells, whereas supplementation with reduced glutathione strengthened the H. suis GGT-mediated inhibition of proliferation. H. suis GGT treatment abolished secretion of IL-4 and IL-17 by CD4+ T cells, without affecting secretion of IFN-γ. Finally, H. suis outer membrane vesicles (OMV) were identified as a possible delivery route of H. suis GGT to lymphocytes residing in the deeper mucosal layers. Thus far, this study is the first to report that the effects on lymphocytes of this enzyme, not only important for H. suis metabolism but also for that of other Helicobacter species, depend on the degradation of two specific substrates: glutamine and reduced glutatione. This will provide new insights into the pathogenic mechanisms of H. suis infection in particular and infection with gastric helicobacters in general

Macropinocytosis of the PDGF β-receptor promotes fibroblast transformation by H-RasG12V

Receptor tyrosine kinase (RTK) signaling is frequently increased in tumor cells, sometimes as a result of decreased receptor down-regulation. The extent to which the endocytic trafficking routes can contribute to such RTK hyperactivation is unclear. Here, we show for the first time that fibroblast transformation by H-RasG12V induces the internalization of platelet-derived growth factor β-receptor (PDGFRβ) by macropinocytosis, enhancing its signaling activity and increasing anchorage-independent proliferation. H-RasG12V transformation and PDGFRβ activation were synergistic in stimulating phosphatidylinositol (PI) 3-kinase activity, leading to receptor macropinocytosis. PDGFRβ macropinocytosis was both necessary and sufficient for enhanced receptor activation. Blocking macropinocytosis by inhibition of PI 3-kinase prevented the increase in receptor activity in transformed cells. Conversely, increasing macropinocytosis by Rabankyrin-5 overexpression was sufficient to enhance PDGFRβ activation in nontransformed cells. Simultaneous stimulation with PDGF-BB and epidermal growth factor promoted macropinocytosis of both receptors and increased their activation in nontransformed cells. We propose that H-Ras transformation promotes tumor progression by enhancing growth factor receptor signaling as a result of increased receptor macropinocytosis