Hepatitis C virus modulation of lipid and autophagy pathways

Hepatitis C virus [HCV] infects 170 million people worldwide. We investigated interactions between HCV proteins and cellular proteins involved in autophagy and lipid metabolism. We sought to develop an infection model using patient derived human serum containing HCV and human hepatocytes, Huh7 cells. Using the model, we have shown intracellular expression of incoming HCV RNA (5′ UTR region and region spanning the E1/E2 glycoproteins), expression of the HCV proteins, core and NS5B, and a cellular response to HCV infection. These data suggests this model can be used to analyse the early stage of HCV infection. HCV utilises the autophagy pathway to both establish infection and to complete its life cycle. We investigated HCV interaction with the early stage autophagy protein ATG5. We found that although ATG5 mRNA is unchanged in HCV infected cells, protein expression of ATG5 is significantly upregulated. These data indicated HCV controls the post-transcriptional regulation of ATG5. We used the upstream open reading frame (uORF) and the 5′ UTR region of ATG5 to examine the post-transcriptional regulation. Our data suggest HCV RNA replication either directly or indirectly causes post-transcriptional regulation of the early autophagy protein, ATG5 in a 5′ UTR and uORF independent manner. HCV infection leads to an increase in SREBP controlled genes e.g. HMG-CoA Reductase, cholesterol, LDL and fatty acid synthesis. We hypothesised that HCV infection causes the activation of SREBP pathway by interacting directly or indirectly with proteins involved in the initiation of the pathway. We sought to determine if HCV interacts with SCAP or INSIG. We confirmed a change in LD distribution and HMG-CoA reductase activity as a result of HCV RNA replication. Significantly, we show SCAP protein expression was also altered during HCV RNA replication and HCV core protein possibly interacts with SCAP.

Transhuman education: Sloterdijk's reading of Heidegger's Letter on Humanism

Peter Sloterdijk presented a reading of Heidegger's Letter on Humanism at a conference held at Elmau in 1999. Reinterpreting the meaning of humanism in the light of Heidegger's Letter, Sloterdijk focused his presentation on the need to redefine education as a form of genetic ‘taming’ and proposed what seemed to be support for positive eugenics. Although Sloterdijk claimed that he only wanted to open a debate on the issue, he could not have been surprised at the level of opposition this suggestion aroused. In the weeks following, he blamed Habermas for raising this opposition and for refusing to engage with him openly. Although Luis Arenas has chronicled the aftermath of Sloterdijk's paper, it may be of interest to educators to examine how Heidegger's text is presented. What is this new humanism? If Heidegger's new humanism was based on a mystical attitude towards Being, so Sloterdijk's new humanism was to be based on the materialist principles of a biotechnological age. Unlike Heidegger who rejected technology as yet one further example of the forgetfulness of Being, Sloterdijk seems to embrace technology and the enhancement of the human body and mind as the next great step forward in educational theory. Could he possibly be right? Is education in these times a partner or an opponent of the technological enhancement of the human being? This article tries to identify Sloterdijk's disagreements with Heidegger on the question of the human.