Translation suppression promotes stress granule formation and cell survival in response to cold shock

Cells respond to different types of stress by inhibition of protein synthesis and subsequent assembly of stress granules (SGs), cytoplasmic aggregates that contain stalled translation preinitiation complexes. Global translation is regulated through the translation initiation factor eukaryotic initiation factor 2a (eIF2a) and the mTOR pathway. Here we identify cold shock as a novel trigger of SG assembly in yeast and mammals. Whereas cold shock-induced SGs take hours to form, they dissolve within minutes when cells are returned to optimal growth temperatures. Cold shock causes eIF2a phosphorylation through the kinase PERK in mammalian cells, yet this pathway is not alone responsible for translation arrest and SG formation. In addition, cold shock leads to reduced mitochondrial function, energy depletion, concomitant activation of AMP-activated protein kinase (AMPK), and inhibition of mTOR signaling. Compound C, a pharmacological inhibitor of AMPK, prevents the formation of SGs and strongly reduces cellular survival in a translation-dependent manner. Our results demonstrate that cells actively suppress protein synthesis by parallel pathways, which induce SG formation and ensure cellular survival during hypothermia.

Dynamic oscillation of translation and stress granule formation mark the cellular response to virus infection

Virus infection-induced global protein synthesis suppression is linked to assembly of stress granules (SGs), cytosolic aggregates of stalled translation preinitiation complexes. To study long-term stress responses, we developed an imaging approach for extended observation and analysis of SG dynamics during persistent hepatitis C virus (HCV) infection. In combination with type 1 interferon, HCV infection induces highly dynamic assembly/disassembly of cytoplasmic SGs, concomitant with phases of active and stalled translation, delayed cell division, and prolonged cell survival. Double-stranded RNA (dsRNA), independent of viral replication, is sufficient to trigger these oscillations. Translation initiation factor eIF2a phosphorylation by protein kinase R mediates SG formation and translation arrest. This is antagonized by the upregulation of GADD34, the regulatory subunit of protein phosphatase 1 dephosphorylating eIF2a. Stress response oscillation is a general mechanism to prevent long-lasting translation repression and a conserved host cell reaction to multiple RNA viruses, which HCV may exploit to establish persistence.

Financial Taxes and the Sand in the Wheels of Financialization:Legal Challenges for the EU Directive Implementing Enhanced Cooperation in the Area of Financial Transaction Tax

One of the many results of the Global Financial Crisis was the insight that the financial sector is under-taxed compared to other industries. In light of the huge bailouts and continued subsidies for financial institutions that are characterized as too-big-to-fail demands came on the agenda to make finance pay for the mega-crisis it caused. The most prominent examples of such taxes are a Financial Transaction Tax (FTT) and a Financial Activities Tax (FAT). Possible effects of such taxes on the economic constitution and increasingly in particular on the European Single Market have been discussed controversially over the last decades already. Especially with the decision of eleven EU member states to adapt an FTT using the enhanced cooperation procedure a number of additional legal challenges for implementing such a tax have emerged. This paper analyzes how tax measures of indirectly regulating the financial industry differ, what legal challenges they pose, and what their overall contribution would be in making the financial system more stable and resilient. It also analyzes the legal arguments against enhanced cooperation in this area and the legal issues related to the British lawsuit against the Commission’s Directive proposal in the European Court of Justice on grounds of the extra-territoriality application of tax. The paper concludes that the feasibility of an FTT is legally sound and given the FTT’s advantages over a FAT the EU Directive should be implemented as a first step for a European-wide FTT. However, significant uncertainties about its implementation remain at this stage.

Export Cartels: Is it Legal to Target your Neighbour? Analysis in Light of Recent Case Law

Despite the growing sophistication of antitrust regimes around the world, export cartels benefit from special treatment: they are almost universally tolerated, if not encouraged in the countries of origin. Economists do not offer an unambiguous policy recommendation on how to deal with them in part due to the lack of empirical data. This article discusses arguments for and against export cartels and it identifies the existing gaps in the present regulatory framework. The theoretical part is followed by an analysis of the recent case law: a US cartel challenged with different outcomes in India and South Africa, as well as Chinese export cartels pursued in the USA. The Chinese cases are particularly topical as the conduct at stake, apart from being subject to private antitrust actions before US courts, was also challenged within the WTO dispute settlement framework, pointing out to the existing interface between trade and competition. While the recent developments prove that unaddressed issues tend not to vanish, the new South-North dimension has the potential of placing export cartels again on the international agenda. Pragmatic thinking suggests looking for the solution within the WTO framework.