Jesse Bailey

Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, mice with a targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis

I argue that Heidegger’s account of technology as “enframing” is a helpful lens through which to understand the possible effects and dangers of transhumanism. Without resorting to nebulous concepts such as “dignity;” Heidegger’s analysis can help us understand how new technologies employed to modify the body; brain; and consciousness will enframe our own bodies and identities as something akin to “standing reserve.” Under transhumanism; the body is enframed as an external; technologically modifiable product. I indicate some of the problems that might arise when our own bodies no longer appear as central to our identity as embodied beings. Further; I argue that; by treating aspects of our own consciousness as technologically modifiable; we will be driven into a commodified and inauthentic relation to our identities. By examining the work of prominent transhumanists – including Brad Allenby; Daniel Sarewitz; and Andy Clark – I show how the threat that technology poses can be hidden when the essence of technology is not uncovered in a primordial way. I argue that by threatening to obscure death as a foundational possibility for Dasein; transhumanism poses the danger of hiding the need to develop a free and authentic relation to technology; Truth; and ultimately to Dasein itself.

This paper presents a reading of the political dimensions of Plato’s Cratylus. Following Sallis, I argue that Socrates’ claim that we can achieve a direct access to being unmediated by language is ironic. There is a comedic element to the attempt to transcend language in order to test the names given by the ‘lawgiver’ against a pure awareness of the nature of beings themselves. I show that this account of human life, as always mediated by logos, has a political dimension. Specifically, the paper argues that the mediation performed by Socrates in the dialogue is intended to get us to turn toward one another in the formation of communities of philosophical discourse.

This paper is a response to Christopher Moore’s excellent paper, “Questioning Aristotle’s Radical Account of Σωφροσύνη.” I expand upon some of the themes in the four suggestions Moore makes in his “Four Possible Defenses” of Aristotle that I take to be the most fruitful avenues of research. I then argue that pursuing these avenues will show that Aristotle’s thinking in the Nicomachean Ethics about σωφροσύνη—and virtues in general—cannot be understood by looking only at the early books. I argue that his deeper analysis of virtue and φρόνησις in book VI demand a revaluation of the apparent finality of his comments in book III. Specifically, I argue that the Nicomachean Ethics as a whole is constructed as a dialectical advancement that points to a progressively deepening understanding of the relationship between the discussion of the individual virtues in the early books and the discussion of φρόνησις in book VI must be developed in order to understand Aristotle’s conception of any individual virtue.