Immunodetection of retinoblastoma-related protein and its phosphorylated form in interphase and mitotic alfalfa cells

Plant retinoblastoma-related (RBR) proteins are primarily considered as key regulators of G1/S phase transition, with functional roles in a variety of cellular events during plant growth and organ development. Polyclonal antibody against the C-terminal region of the Arabidopsis RBR1 protein also specifically recognizes the alfalfa 115 kDa MsRBR protein, as shown by the antigen competition assay. The MsRBR protein was detected in all cell cycle phases, with a moderate increase in samples representing G2/M cells. Antibody against the human phospho-pRb peptide (Ser807/811) cross-reacted with the same 115 kDa MsRBR protein and with the in vitro phosphorylated MsRBR protein C-terminal fragment. Phospho-MsRBR protein was low in G1 cells. Its amount increased upon entry into the S phase and remained high during the G2/M phases. Roscovitine treatment abolished the activity of alfalfa MsCDKA1;1 and MsCDKB2;1, and the phospho-MsRBR protein level was significantly decreased in the treated cells. Colchicine block increased the detected levels of both forms of MsRBR protein. Reduced levels of the MsRBR protein in cells at stationary phase or grown in hormone-free medium can be a sign of the division-dependent presence of plant RBR proteins. Immunolocalization of the phospho-MsRBR protein indicated spots of variable number and size in the labelled interphase nuclei and high signal intensity of nuclear granules in prophase. Structures similar to phospho-MsRBR proteins cannot be recognized in later mitotic phases. Based on the presented western blot and immunolocalization data, the possible involvement of RBR proteins in G2/M phase regulation in plant cells is discussed

Models in Science and Engineering: Imagining, Designing and Evaluating Representations

How can one learn about particular phenomena by using models? This is the central question of the present book. One brief answer is that one can learn about phenomena by using models if these models represent the phenomena. A longer answer will be presented in the individual chapters. Answering this question involves not only (partially) explaining what representation is, but also how the notions of representation and evaluation are connected in the context of modeling. The thesis includes a fresh look at so-called similarity views on representation and a discussion of fictionalist accounts of modeling, while expanding on the general framework of indirect representation. A case study in bioengineering is used to show that the indirect view of representation must acknowledge a distinction between two directions of fit in relations between vehicles and targets. In this context the notion of design is interpreted as a relation between a vehicle and a target, thereby connecting ideas from philosophy of science with ideas from philosophy of technology. In the concluding chapters fictionalist accounts of modeling are discussed. These accounts are criticized from an epistemological point of view but the accounts’ foundational theory of make-believe is constructively applied to a case study in climate modeling.Ethics & Philosophy of Technolog

Differential antiproliferative mechanisms of novel derivative of benzimidazo[1,2-alpha]quinoline in colon cancer cells depending on their p53 status

In the present article, we describe a mechanistic study of a novel derivative of N-amidino-substituted benzimidazo[1,2-alpha]quinoline in two human colorectal cancer cell lines differing in p53 gene status. We used a proteomic approach based on two-dimensional gel electrophoresis coupled with mass spectrometry to complement the results obtained by common molecular biology methods for analyzing cell proliferation, cell cycle, and apoptosis. Tested quinoline derivative inhibited colon cancer cell growth, whereby p53 gene status seemed to be critical for its differential response patterns. DNA damage and oxidative stress are likely to be the common triggers of molecular events underlying its antiproliferative effects. In HCT 116 (wild-type p53), this compound induced a p53-dependent response resulting in accumulation of the G(1)- and S-phase cells and induction of apoptosis via both caspase-3-dependent and caspase-independent pathways. Quinoline derivative triggered transient, p53-independent G(2)-M arrest in mutant p53 cells (SW620) and succeeding mitotic transition, whereby these cells underwent cell death probably due to aberrant mitosis (mitotic catastrophe). Proteomic approach used in this study proved to be a valuable tool for investigating cancer cell response to newly synthesized compound, as it specifically unraveled some molecular changes that would not have been otherwise detected (e.g., up-regulation of the p53-dependent chemotherapeutic response marker maspin in HCT 116 and impairment in ribosome biogenesis in SW620). Finally, antiproliferative effects of tested quinoline derivative on SW620 cells strongly support its possible role as an antimetastatic agent and encourage further in vivo studies on the chemotherapeutic potential of this compound against colorectal carcinoma

Representation and similarity: Suarez on necessary and sufficient conditions of scientific representation

The notion of scientific representation plays a central role in current debates on modeling in the sciences. One or maybe the major epistemic virtue of successful models is their capacity to adequately represent specific phenomena or target systems. According to similarity views of scientific representation, models should be similar to their corresponding targets in order to represent them. In this paper, Suarez’s arguments against similarity views of representation will be scrutinized. The upshot is that the intuition that scientific representation involves similarity is not refuted by the arguments. The arguments do not make the case for the strong claim that similarity between vehicles and targets is neither necessary nor sufficient for scientific representation. Especially, one claim that a similarity view wants to uphold, still, is the following thesis: only if a vehicle is similar to a target in relevant respects and to a specific degree of similarity then the vehicle is a scientific representation of that target.Ethics & Philosophy of Technolog

Reimagining the future of engineering

Reimagining suggests the idea of opening up new, unconventional spaces of possibilities for an activity or an entity that already exists. This chapter sketches some ideas of the future of engineering in various aspects: designing, action, problem framing, professional and disciplinary identity, and the training of future engineers. The thoughts presented here are intended to be inconclusive. They take up and address the question of reimagining the future of engineering in order to inspire future dialogue between philosophers and engineers.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Ethics & Philosophy of Technolog