The Malady of Revolutions: Yellow Fever in the Atlantic World, 1793-1828

Between the late eighteenth and early nineteenth century, revolutions in the Americas and Europe rocked the Atlantic world and introduced new patterns of trade, warfare and migration. The patterns of long-distance trade that knitted the Atlantic World together, and the warfare and political dislocation that threatened to tear it apart also transported yellow fever far from its African origins and transformed it into an alarming health crisis that engulfed the Caribbean, new United States and southern Europe. This dissertation examines the new ecology for health management that contemporaries created to deal with the crisis. Existing scholarship on medical responses to the yellow fever pandemics focuses on imperial, local or new national contexts. Using the framework of Atlantic History, this dissertation explores how, not unlike yellow fever itself, knowledge about the disease and practices became subject to the global circulation and activities of physicians, military and naval personnel, political refugees, merchants, consuls and lay travelers who connected the diverse ports that hosted outbreaks of the disease. As a result of these actors’ complex movements and dislocations during this period, management of the health crisis became a product of exchanges that cut across the new ideological and international boundaries that began to crystallize in this period. What emerged out of the Age of Atlantic Revolutions was a rich tapestry of vibrant medical networks, literature and practices that spanned across new national divides

Loss of Tbk1 kinase activity protects mice from diet-induced metabolic dysfunction

Objective: TANK Binding Kinase 1 (TBK1) has been implicated in the regulation of metabolism through studies with the drug amlexanox, an inhibitor of the IκB kinase (IKK)-related kinases. Amlexanox induced weight loss, reduced fatty liver and insulin resistance in high fat diet (HFD) fed mice and has now progressed into clinical testing for the treatment and prevention of obesity and type 2 diabetes. However, since amlexanox is a dual IKKε/TBK1 inhibitor, the specific metabolic contribution of TBK1 is not clear. Methods: To distinguish metabolic functions unique to TBK1, we examined the metabolic profile of global Tbk1 mutant mice challenged with an obesogenic diet and investigated potential mechanisms for the improved metabolic phenotype. Results and conclusion: We report that systemic loss of TBK1 kinase function has an overall protective effect on metabolic readouts in mice on an obesogenic diet, which is mediated by loss of an inhibitory interaction between TBK1 and the insulin receptor. Keywords: TBK1, IKKε, Obesity, Insulin, Insulin resistance, Metabolis

Mechanisms involved in the regulation of free fatty acid release from isolated human fat cells by acylation-stimulating protein and insulin

The effects of acylation-stimulating protein (ASP) and insulin on free fatty acid (FFA) release from isolated human fat cells and the signal transduction pathways to induce these effects were studied. ASP and insulin inhibited basal and norepinephrine-induced FFA release by stimulating fractional FFA re-esterification (both to the same extent) and by inhibiting FFA produced during lipolysis (ASP to a lesser extent than insulin). Protein kinase C inhibition influenced none of the effects of ASP or insulin. Phosphatidylinositol 3-kinase inhibition counteracted the effects of insulin but not of ASP. Phosphodiesterase 3 (PDE3) activity was stimulated by ASP and insulin, whereas PDE4 activity was slightly increased by ASP only. Selective PDE3 inhibition reversed the effects of both ASP and insulin on fractional FFA re-esterification and lipolysis. Selective PDE4 inhibition slightly counteracted the ASP but not the effect of insulin on fractional FFA re-esterification and did not prevent the action of ASP or insulin on lipolysis. Thus, ASP and insulin play a major role in regulating FFA release from fat cells as follows: insulin by stimulating fractional FFA re-esterification and inhibiting lipolysis and ASP mainly by stimulating fractional FFA re-esterification. For both ASP and insulin these effects on FFA release are mediated by PDE3, and for ASP PDE4 might also be involved. The signaling pathway preceding PDE is not known for ASP but involves phosphatidylinositol 3-kinase for insulin

The history of Atlantic science : collective reflections from the 2009 Harvard seminar on Atlantic history

For the purposes of this review essay, which seeks to capture the spirit of those early conversations in Cambridge, we propose calling the assemblages and interactions of the peoples, objects, institutions, and techniques that resulted in and from colonization during the early modern period ‘‘Atlantic science.’’ We recognize, of course, that not all colonization was bounded by an Atlantic frame. However, in terms of timing, scale, and scope, no other cluster of imperial enterprises can be compared with the conquest and colonization of the Americas in the sixteenth, seventeenth, and eighteenth centuries. What made colonization in the Atlantic unique was that it involved the voluntary migration of more than two million Europeans, the forced migration of more than ten million Africans, the creation of a vast network of interconnected centers, and the political incorporation ofmuch of the hemisphere into the Western world, all between 1500 and 1825. Nothing of this scale has happened anywhere else in the early modern period. The Atlantic Ocean, rather than Europe, became the center of that world. And so, we see the Atlantic world as an outcome of this colonizing process