Reversible Fusion Proteins as a Tool to Enhance Uptake of Virus-Functionalized LbL Microcarriers

For the efficient treatment of an increasing number of diseases the development of new therapeutics as well as novel drug delivery systems is essential. Such drug delivery systems (DDS) must not only consider biodegradability and protective packaging but must also target and control the release of active substances, which is one of the most important points in DDS application. We highlight the improvement of these key aspects, the increased interaction rate of Layer-by-Layer (LbL) designed microcarriers as a promising DDS after functionalization with vesicular stomatitis virus (VSV). We make use of the unique conformational reversibility of the fusion protein of VSV as a surface functionalization of LbL microcarriers. This reversibility allows for VSV to be used both as a tool for assembly onto the DDS and as an initiator for an efficient cellular uptake. We could show that the evolutionary optimized viral fusion machinery can be successfully combined with a biophysical DDS for optimization of its cellular interaction

Influence of Growth Characteristics of Induced Pluripotent Stem Cells on Their Uptake Efficiency for Layer-by-Layer Microcarriers

Induced pluripotent stem cells (iPSCs) have the ability to differentiate into any specialized somatic cell type, which makes them an attractive tool for a wide variety of scientific approaches, including regenerative medicine. However, their pluripotent state and their growth in compact colonies render them difficult to access and, therefore, restrict delivery of specific agents for cell manipulation. Thus, our investigation focus was set on the evaluation of the capability of layer-by-layer (LbL) designed microcarriers to serve as a potential drug delivery system to iPSCs, as they offer several appealing advantages. Most notably, these carriers allow for the transport of active agents in a protected environment and for a rather specific delivery through surface modifications. As we could show, charge and mode of LbL carrier application as well as the size of the iPSC colonies determine the interaction with and the uptake rate by iPSCs. None of the examined conditions had an influence on iPSC colony properties such as colony morphology and size or maintenance of pluripotent properties. An overall interaction rate of LbL carriers with iPSCs of up to 20% was achieved. Those data emphasize the applicability of LbL carriers for stem cell research. Additionally, the potential use of LbL carriers as a promising delivery tool for iPSCs was contrasted to viral particles and liposomes. The identified differences among those delivery tools have substantiated our major conclusion that LbL carrier uptake rate is influenced by characteristic features of the iPSC colonies (most notably colony size) in addition to their surface charges

Transfer of delictual liability in competition law

Transfer of delictual liability in competition law The issue of delictual liability for anti-competitive practices and subsequent identification of party which is to be penalized for them is, with regard to effective protection of competition, a crucial one. However, it is also a topic which is, with a few notable exceptions, often addressed only superficially. This work therefore aims to perform thorough analysis of rules applicable to transfer of delictual liability both on European and Czech national level. For this purpose, it is divided into two major and comparatively separate parts. First of them is devoted to a detailed analysis of the European court of justice case-law related to the possibility of transfer of liability from the original infringer to a different legal entity. The aim is not only to identify particular criteria, which may affect such transfer of liability, but also to illustrate the direction in which the case-law of the European court of justice evolved and in which it is probable to continue heading in the future. The second part of this work deals with regulation of the transfer of liability within the Czech legal framework, commencing with adoption of Act no. 63/1991 Coll., on the Protection of Competition, up to the present. Considering the decisive influence of the..

Additional file 3: of Gene expression profiling of rubella virus infected primary endothelial cells of fetal and adult origin

Ranking of commonly up- and down-regulated genes in the endothelial cells following RV infection. (PDF 52 kb

Infection of iPSC Lines with Miscarriage-Associated Coxsackievirus and Measles Virus and Teratogenic Rubella Virus as a Model for Viral Impairment of Early Human Embryogenesis

Human induced pluripotent stem cell (iPSC) lines are a promising model for the early phase of human embryonic development. Here, their contribution to the still incompletely understood pathogenesis of congenital virus infections was evaluated. The infection of iPSC lines with miscarriage-associated coxsackievirus B3 (CVB3) and measles virus (MV) was compared to the efficient teratogen rubella virus (RV). While CVB3 and MV were found to be cytopathogenic on iPSC lines, RV replicated without impairment of iPSC colony morphology and integrity. This so far outstanding course of infection enabled maintenance of RV-infected iPSC cultures over several passages and their subsequent differentiation to ectoderm, endoderm, and mesoderm. A modification of the metabolic profile of infected iPSC lines was the only common aspect for all three viruses. This study points toward two important aspects. First, iPSC lines represent a suitable cell culture model for early embryonic virus infection. Second, metabolic activity represents an important means for evaluation of pathogen-associated alterations in iPSC lines