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Members of the myocardin family bind to the transcription factor serum response factor (SRF) and act as coactivators controlling genes of relevance for myogenic differentiation and motile function. Binding of SRF to DNA is mediated by genetic elements called CArG boxes, found often but not exclusively in muscle and growth controlling genes. Studies aimed at defining the full spectrum of these CArG
Phenotypic modulation of smooth muscle cells (SMCs) plays a key role in vascular disease, including atherosclerosis. Several transcription factors have been suggested to regulate phenotypic modulation of SMCs but the decisive mechanisms remain unknown. Recent reports suggest that specific microRNAs (miRNAs) are involved in SMC differentiation and vascular disease but the global role of miRNAs in p
OBJECTIVE: Regulation of vascular smooth muscle (VSM) proliferation and contractile differentiation is an important factor in vascular development and subsequent cardiovascular diseases. Recently, microRNAs (miRNAs) have been shown to regulate fundamental cellular processes in a number of cell types, but the integrated role of miRNAs in VSM in blood vessels is unknown. Here, we investigated the ro
Despite recent advances in understanding store-operated calcium entry (SOCE) regulation, the fundamental question of how ER morphology affects this process remains unanswered. Here we show that the loss of RTN4, is sufficient to alter ER morphology and severely compromise SOCE. Mechanistically, we show this to be the result of defective STIM1-Orai1 coupling because of loss of ER tubulation and red
In this study, we present integrated quantitative proteome, transcriptome, and methylome analyses of hematopoietic stem cells (HSCs) and four multipotent progenitor (MPP) populations. From the characterization of more than 6,000 proteins, 27,000 transcripts, and 15,000 differentially methylated regions (DMRs), we identified coordinated changes associated with early differentiation steps. DMRs show
Infections are associated with extensive platelet consumption, representing a high risk for health. However, the mechanism coordinating the rapid regeneration of the platelet pool during such stress conditions remains unclear. Here, we report that the phenotypic hematopoietic stem cell (HSC) compartment contains stem-like megakaryocyte-committed progenitors (SL-MkPs), a cell population that shares
Regulatory T cells (Tregs) differentiate in the thymus, but the mechanisms that control this process are not fully understood. We generated a comprehensive quantitative and differential proteome of murine Tregs and conventional T cells. We identified 5225 proteins, 164 of which were differentially expressed in Tregs. Together with the comparative analysis of proteome and gene expression data, we i
Hematopoietic stem cells possess lifelong self-renewal activity and generate multipotent progenitors that differentiate into lineage-committed and subsequently mature cells. We present a comparative transcriptome analysis of ex vivo isolated mouse multipotent hematopoietic stem/progenitor cells (Lin(neg)SCA-1(+)c-KIT(+)) and myeloid committed precursors (Lin(neg)SCA-1(neg)c-KIT(+)). Our data displ
The field of proteomics is progressing at a rapid pace, developing from primarily a specialist technology to a valuable tool in biological research. Importantly, the establishment of mass spectrometry as a quantitative method, miniaturisation of liquid chromatography techniques, and improved sensitivity of mass-spectrometric instrumentation now enable near-complete monitoring of cellular proteome
Trust within teams is a central performance driver in product innovation. In this paper, we examine the antecedents to and performance implications of trust in firms engaged in radical innovation compared to those working towards incremental innovations. Our findings suggest that systematic processes and structures are significantly linked to trust in firms conducting radical innovation, but not s
Based on a longitudinal case study of four interorganizational product development collaborations, this paper identifies a lure to cross-functional integration that has hereto been neglected. In particular, findings suggest that when the buyer firm separates the Research and Development (R&D) Department from the Procurement Department, the two departments play a good cop-bad cop strategy towar
This paper addresses the challenge of striking a balance between, on one hand, mitigating uncertainty through the existence of systematic processes and structures and, on the other, stimulating creativity through allowable variation in work processes and structures. Both objectives are fundamental aspects of product development work. Our main finding is that both objectives can be achieved simulta
Hardwood spent sulphite liquors (HSSLs) are by-products from the pulping industry rich in pentoses, which are not yet fully exploited for bioprocessing, namely for the production of bioethanol. The sustainable fermentation of pentoses into bioethanol is a challenge to overcome. Besides sugars, HSSLs contains inhibitors that decrease the possibility of bioprocessing of these by-products. Neverthele
Dame Margaret Drabble’s The Millstone can profitably be read as shedding light on personal identity and moral development as well as how these connect to contemporary society, history, friendship, self-knowledge and self-deception in a way that ought to be of interest to classic perfectionist theories, i.e. ethical theories that develop an account of ethics informed by an account of the good human
