Dr Carolyn Lam:                Welcome to Circulation On The Run, your weekly podcast summary and backstage pass to the Journal and its editors. I'm Dr Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr Gregory Hundley:       I'm Greg Hundley, also associate editor from the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr Carolyn Lam:                Greg, what do you think is the association between preeclampsia and hypertensive diseases of pregnancy and cardiovascular disease and future? Well, we're going to find out in a large U.K. pregnancy cohort of linked electronic health records, the CALIBER Study, but that's a feature discussion that's coming right up.                                                 I think we need to start by discussing this week's hot issue. For the first paper, we know that the incidents of acute cardiovascular complications are highly dependent on the time of day. Greg, have you ever wondered what mechanisms drive the rhythmicity of ischemic vascular events? Dr Gregory Hundley:       You know what, Carolyn, I had a dream about that and I think that somehow maybe it might be something to do with leukocytes. Dr Carolyn Lam:                Good guess, Greg. Well, Dr Christoph Scheiermann and his colleagues from University of Geneva looked at this and they examined the role of rhythmic leukocyte adhesions and what those play in different vascular beds. They did this by evaluating leukocyte recruitment in vivo with real time, multichannel fluorescence intravital microscopy of a TNF alpha induced acute inflammation Murine model.                                                 Now, they also used ablation of sympathetic nerves or adrenergic receptors to assess their relevance for these rhythmic leukocyte adhesions. Basically what they found was that leukocytes adhere to arteries and veins following a circadian rhythm in mice, with adhesion peaking in the arteries in the morning and in the veins at night.                                                 These peaks in leukocyte adhesion at different times in the two vascular beds were associated with increased vascular inflammation and shortened times to local basal occlusive events occurring out of phase between the arteries and the veins. The differences in cell adhesion molecules and leukocyte adhesions were ablated when disrupting the sympathetic nerves, thus demonstrating their critical role in this process and the importance of beta2-adrenergic receptor signaling. Neat, huh? Dr Gregory Hundley:       Really neat. It's interesting how that ties together sympathetic nerve activity and leukocyte adhesion. Dr Carolyn Lam:                You got a paper? Dr Gregory Hundley:       I've got a paper to discuss and it's from Dr John Cooke at the Houston Methodist Research Institute. It's involving nuclear S-nitrosylation and how that defines an optimal zone for inducing pluripotency, the ability to generate induced pluripotent stem cells or I.P.S.C's from somatic cells as it enhanced the field of regenerative medicine.                                                 It has facilitated studies of development in differentiation, promoted insights into pathobiology, and generated a novel platform for drug discovery and testing. In fact, work in this area has been sufficient to induce nuclear reprogramming to pluripotency and galvanized our whole scientific community. Recently in 2012, this work was recognized by the Nobel Prize for physiology or medicine. Dr Carolyn Lam:                Wow. What did this week's paper show in this area? Dr Gregory Hundley:       Well, Carolyn, in this study, the team identified an optimal zone. They call it the Goldilocks zone of innate immune activation for nuclear reprogramming to pluripotency. The authors believe that this Goldilocks zone for nuclear reprogramming may have broad relevance for epigenetic control, for regenerative processes, and for the pathob