Pseudorandom Sequences from Elliptic Curves

In this article we will generalize some known constructions to produce pseudorandom sequences with the aid of elliptic curves. We will make use of both additive and multiplicative characters on elliptic curves

Quantifying extracellular matrix turnover in human lung scaffold cultures

Remodelling of the extracellular matrix is accomplished by altering the balance between matrix macromolecule production and degradation. However, it is not well understood how cells balance production of new matrix molecules and degradation of existing ones during tissue remodelling and regeneration. In this study, we used decellularized lung scaffolds repopulated with allogenic lung fibroblasts cultured with stable isotope labelled amino acids to quantify the balance between matrix production and degradation at a proteome-wide scale. Specific temporal dynamics of different matrisome proteins were found to correspond to the proliferative activity of the repopulating cells and the degree of extracellular deposition. The remodeling of the scaffold was characterized by an initial phase with cell proliferation and high production of cell adhesion proteins such as emilin-1 and fibronectin. Extended culture time resulted in increased levels of core matrisome proteins. In a comparison with monolayer cultures on plastic, culture in lung scaffolds lead to a pronounced accumulation of proteoglycans, such as versican and decorin, resulting in regeneration of an extracellular matrix with greater resemblance to native lung tissue compared to standard monolayer cultures. Collectively, the study presents a promising technique for increasing the understanding of cell- extracellular matrix interactions under healthy and diseased conditions

A combinatorial screen of the CLOUD uncovers a synergy targeting the androgen receptor

International audienceApproved drugs are invaluable tools to study biochemical pathways, and further characterization of these compounds may lead to repurposing of single drugs or combinations. Here we describe a collection of 308 small molecules representing the diversity of structures and molecular targets of all FDA-approved chemical entities. The CeMM Library of Unique Drugs (CLOUD) covers prodrugs and active forms at pharmacologically relevant concentrations and is ideally suited for combinatorial studies. We screened pairwise combinations of CLOUD drugs for impairment of cancer cell viability and discovered a synergistic interaction between flutamide and phenprocoumon (PPC). The combination of these drugs modulates the stability of the androgen receptor (AR) and resensitizes AR-mutant prostate cancer cells to flutamide. Mechanistically, we show that the AR is a substrate for γ-carboxylation, a post-translational modification inhibited by PPC. Collectively, our data suggest that PPC could be repurposed to tackle resistance to antiandrogens in prostate cancer patients

Perspectives on the Feasibility of Using Enzymes for Pharmaceutical Removal in Wastewater

This particular chapter spotlights the growing environmental concerns and hazardous consequences of numerous organic contaminants so-called emerging contaminants (ECs). These ECs are being detected, though in different quantities, in different environmental matrices and wastewater treatment systems. With ever-increasing awareness, people are now more concerned about the wide-spread distribution of pharmaceutically related active compounds in water matrices. In turn, the free flow of ECs in water matrices poses notable adverse effects on human, aquatic animals, and naturally occurring plants, even at very small concentrations. Due to inadequacies and ineffectiveness of, in practice, physical and chemical-based remediation processes, robust treatment approaches, such as microorganisms and their novel enzyme-based degradation/removal of ECs, are of supreme interest. This chapter focuses on various pharmaceutically related ECs and their efficient mitigation from water matrices. Following a brief introduction, the focus is given to two main treatment approaches, i.e., (1) remediation of pharmaceutically active compounds by crude (pristine) and purified enzymes (i.e., lignin peroxidase, manganese peroxidase, soybean peroxidase, horseradish peroxidase, and laccases) and (2) immobilized enzyme-assisted degradation of pharmaceutically active compounds.Peer reviewe