Microparticle-mediated transfer of the viral receptors CAR and CD46, and the CFTR channel in a CHO cell model confers new functions to target cells

Cell microparticles (MPs) released in the extracellular milieu can embark plasma membrane and intracellular components which are specific of their cellular origin, and transfer them to target cells. The MP-mediated, cell-to-cell transfer of three human membrane glycoproteins of different degrees of complexity was investigated in the present study, using a CHO cell model system. We first tested the delivery of CAR and CD46, two monospanins which act as adenovirus receptors, to target CHO cells. CHO cells lack CAR and CD46, high affinity receptors for human adenovirus serotype 5 (HAdV5), and serotype 35 (HAdV35), respectively. We found that MPs derived from CHO cells (MP-donor cells) constitutively expressing CAR (MP-CAR) or CD46 (MP-CD46) were able to transfer CAR and CD46 to target CHO cells, and conferred selective permissiveness to HAdV5 and HAdV35. In addition, target CHO cells incubated with MP-CD46 acquired the CD46-associated function in complement regulation. We also explored the MP-mediated delivery of a dodecaspanin membrane glycoprotein, the CFTR to target CHO cells. CFTR functions as a chloride channel in human cells and is implicated in the genetic disease cystic fibrosis. Target CHO cells incubated with MPs produced by CHO cells constitutively expressing GFP-tagged CFTR (MP-GFP-CFTR) were found to gain a new cellular function, the chloride channel activity associated to CFTR. Time-course analysis of the appearance of GFP-CFTR in target cells suggested that MPs could achieve the delivery of CFTR to target cells via two mechanisms: the transfer of mature, membrane-inserted CFTR glycoprotein, and the transfer of CFTR-encoding mRNA. These results confirmed that cell-derived MPs represent a new class of promising therapeutic vehicles for the delivery of bioactive macromolecules, proteins or mRNAs, the latter exerting the desired therapeutic effect in target cells via de novo synthesis of their encoded proteins

Tax Competition within the European Union Revisited Is the Relaunched CCCTB a Solution?

The author addresses the phenomenon of taxable profit-shifting operations undertaken by multinationals in response to countries competing for corporate tax bases within the European Union. The central question is whether this might be a relic of the past when the European Commission\xe2\x80\x99s proposals of 25 October 2016 relaunching the Commission\xe2\x80\x99s original proposal for a Council Directive on a Common Consolidated Corporate Tax Base sees the light of day. Or would the EU-wide corporate tax system provide incentives for multinationals to pursue artificial tax base-shifting practices within the EU, potentially invigorating the risk of undue governmental tax competition responses? The author\xe2\x80\x99s tentative answer on the potential for artificial base shifting and undue tax competition is in the affirmative. Today, the issue of harmful tax competition within the EU seems to have been pushed back as a result of the soft law approaches that were initiated in the late 1990s and early 2000s, and the recent implementation of a number of the OECD\xe2\x80\x99s anti-BEPS initiatives on an EU-wide basis. But things might change if the CCCTB relaunch proposal as currently drafted enters into force. There may be a risk that substantial parts of the EU tax base would instantly become mobile as of that day. As the EU Member States at that time seem to have only a single tool available to respond to this \xe2\x80\x93 the tax rate \xe2\x80\x93 that may perhaps initiate an undesirable race for the EU tax base, at least theoretically