Nature, Virginia\u27s Economy, and the Climate Threat

The Commission\u27s charge is to propose solutions to you for climate-related issues facing the Commonwealth. Our Symposium today also takes up that challenge. In this booklet you will find research and recommendations for you -- and all of Virginia\u27s governing bodies – for how best to protect our state\u27s priceless and economically essential natural heritage as climate changes disrupt our ecosystems. Paper prepared for Environmental Studies Senior Seminar. Faculty advisers: Dr. Peter D. Smallwood and Stephen P. Nas

Engineering protein processing of the mammary gland to produce abundant hemophilia B therapy in milk

Both the low animal cell density of bioreactors and their ability to post-translationally process recombinant factor IX (rFIX) limit hemophilia B therapy to transgenic pigs to make rFIX in milk at about 3,000-fold higher output than provided by industrial bioreactors. However, this resulted in incomplete γ-carboxylation and propeptide cleavage where both processes are transmembrane mediated. We then bioengineered the co-expression of truncated, soluble human furin (rFurin) with pro-rFIX at a favorable enzyme to substrate ratio. This resulted in the complete conversion of pro-rFIX to rFIX while yielding a normal lactation. Importantly, these high levels of propeptide processing by soluble rFurin did not preempt γ-carboxylation in the ER and therefore was compartmentalized to the Trans-Golgi Network (TGN) and also to milk. The Golgi specific engineering demonstrated here segues the ER targeted enhancement of γ-carboxylation needed to biomanufacture coagulation proteins like rFIX using transgenic livestock

Engineering protein processing of the mammary gland to produce abundant hemophilia B therapy in milk

Both the low animal cell density of bioreactors and their ability to post-translationally process recombinant factor IX (rFIX) limit hemophilia B therapy to transgenic pigs to make rFIX in milk at about 3,000-fold higher output than provided by industrial bioreactors. However, this resulted in incomplete γ-carboxylation and propeptide cleavage where both processes are transmembrane mediated. We then bioengineered the co-expression of truncated, soluble human furin (rFurin) with pro-rFIX at a favorable enzyme to substrate ratio. This resulted in the complete conversion of pro-rFIX to rFIX while yielding a normal lactation. Importantly, these high levels of propeptide processing by soluble rFurin did not preempt γ-carboxylation in the ER and therefore was compartmentalized to the Trans-Golgi Network (TGN) and also to milk. The Golgi specific engineering demonstrated here segues the ER targeted enhancement of γ-carboxylation needed to biomanufacture coagulation proteins like rFIX using transgenic livestock

Placebo from an enactive perspective

Due to their complexity and variability, placebo effects remain controversial. We suggest this is also due to a set of problematic assumptions (dualism, reductionism, individualism, passivity). We critically assess current explanations and empirical evidence and propose an alternative theoretical framework—the enactive approach to life and mind—based on recent developments in embodied cognitive science. We review core enactive concepts such as autonomy, agency, and sense-making. Following these ideas, we propose a move from binary distinctions (e.g., conscious vs. non-conscious) to the more workable categories of reflective and pre-reflective activity. We introduce an ontology of individuation, following the work of Gilbert Simondon, that allow us to see placebo interventions not as originating causal chains, but as modulators and triggers in the regulation of tensions between ongoing embodied and interpersonal processes. We describe these interrelated processes involving looping effects through three intertwined dimensions of embodiment: organic, sensorimotor, and intersubjective. Finally, we defend the need to investigate therapeutic interactions in terms of participatory sense-making, going beyond the identification of individual social traits (e.g., empathy, trust) that contribute to placebo effects. We discuss resonances and differences between the enactive proposal, popular explanations such as expectations and conditioning, and other approaches based on meaning responses and phenomenological/ecological ideas