The poverty of journal publishing

The article opens with a critical analysis of the dominant business model of for-profit, academic publishing, arguing that the extraordinarily high profits of the big publishers are dependent upon a double appropriation that exploits both academic labour and universities’ financial resources. Against this model, we outline four possible responses: the further development of open access repositories, a fair trade model of publishing regulation, a renaissance of the university presses, and, finally, a move away from private, for-profit publishing companies toward autonomous journal publishing by editorial boards and academic associations. </jats:p

In vitro interaction network of a synthetic gut bacterial community

A key challenge in microbiome research is to predict the functionality of microbial communities based on community membership and (meta)-genomic data. As central microbiota functions are determined by bacterial community networks, it is important to gain insight into the principles that govern bacteria-bacteria interactions. Here, we focused on the growth and metabolic interactions of the Oligo-Mouse-Microbiota (OMM12) synthetic bacterial community, which is increasingly used as a model system in gut microbiome research. Using a bottom-up approach, we uncovered the directionality of strain-strain interactions in mono- and pairwise co-culture experiments as well as in community batch culture. Metabolic network reconstruction in combination with metabolomics analysis of bacterial culture supernatants provided insights into the metabolic potential and activity of the individual community members. Thereby, we could show that the OMM12 interaction network is shaped by both exploitative and interference competition in vitro in nutrient-rich culture media and demonstrate how community structure can be shifted by changing the nutritional environment. In particular, Enterococcus faecalis KB1 was identified as an important driver of community composition by affecting the abundance of several other consortium members in vitro. As a result, this study gives fundamental insight into key drivers and mechanistic basis of the OMM12 interaction network in vitro, which serves as a knowledge base for future mechanistic in vivo studies

The Regulation of Th2 Cytokine Genes: Functional and Comparative Genomic Analysis

Immune responses to extracellular pathogens are mediated by the Th2 cytokines Interleukin (IL)-4, IL-5 and IL-13, which are typically expressed by T helper type-2 (Th2) cells. The genes for IL4, IL5 and IL13 are grouped together within 150 kb of human chromosome 5q31, and their expression is regulated at multiple levels to ensure these proteins are rapidly secreted together in response to antigenic stimulation. Indeed, co-expression of these cytokines is vital for effective Th2 immunity and pathogen expulsion. This dissertation combines comparative approaches with molecular experimentation to provide novel insights into the mechanisms that govern the co-expression of Th2 cytokine genes.Conserved non-coding sequence (CNS)-1 has been shown to coordinately regulate the expression of all three Th2 cytokines genes. Using reporter assays with CNS-1 deletion mutants, we mapped a potent, 68 bp T cell activation-dependent enhancer core within CNS-1, which drives transcription of both human IL13 and IL4. The CNS-1 core contained three CREB binding sites to which CREB and the coactivators CREB binding protein and p300 were recruited in vivo upon T cell activation. Furthermore, CBP and p300 were required for CNS-1 core activity. These data define the region within CNS-1 responsible for enhancement of both IL4 and IL13 transcription in response to T cell receptor signaling.Coordinated expression of Th2 cytokine genes is rooted in an extensive array of cis-regulatory regions. We performed a multi-species comparative analysis of the Th2 cytokine gene cluster to locate CNSs, which may represent cis-regulatory elements, and identify transcription factor binding sites shared among them, which may mediate coregulated expression. Sites for GATA transcription factors were the most prevalent and widely distributed throughout the Th2 cytokine locus, consistent with the known role of GATA3 as a Th2 master switch. Notably, binding motifs for ETS proteins were also predicted within several Th2 CNSs. The majority of these sites bound Ets-1 both in vitro and in vivo in murine Th2 cells. Importantly, IL-4, IL-5, and IL-13 expression was markedly decreased in Th2 cells from Ets-1-/-mice. These data suggest an important and novel role for Ets-1 in the concerted expression of Th2 cytokine genes