A successful Wall Street trader turned neuroscientist reveals how risk taking and stress transform our body chemistry
Before he became a world-class scientist, John Coates ran a derivatives trading desk in New York City. He used the expression "the hour between dog and wolf" to refer to the moment of Jekyll-and-Hyde transformation traders passed through when under pressure. They became cocky and irrationally risk-seeking when on a winning streak, tentative and risk-averse when cowering from losses. In a series of groundbreaking experiments, Coates identified a feedback loop between testosterone and success--one that can cloud men's judgment in high-pressure decision-making. Coates demonstrates how our bodies produce the fabled gut feelings we so often rely on, how stress in the workplace can impair our judgment and even damage our health, and how sports science can help us toughen our bodies against the ravages of stress. Revealing the biology behind bubbles and crashes, "The Hour Between Dog and Wolf "sheds new and surprising light on issues that affect us all.

The lymphatic system develops and functions in parallel with the blood circulatory system (termed the "hemovasculature") and accomplishes transport of interstitial fluids, dietary lipids, and reverse transport of cholesterol, immune cells, and antigens-providing a critical homeostatic fluid balance and transmission of immune cells and mediators back to the cardiovascular system. Although the daily flow of lymph (normally 1-2 L/day under unstressed conditions) is far lower than that of daily blood flow (which is 7,500 L/day), without the adequate functioning of the lymphatics, virtually all organs and tissues would acutely suffer many different physical and inflammatory stresses ranging from edema to organ system failure. Although blood and lymphatic vessels often form in anatomic parallels to one another, our knowledge of the workings of the lymphatic system, the fine structure of lymphatic networks, how they function in different organs, and how they are regulated physiologically and immunologically are far from parallel; our knowledge of the lymphatic system still remains at only a tiny fraction of what is understood about the cardiovascular system. Although both the cardiovascular and lymphatic systems are important transport systems, what they transport and how they transport and propel these very different cargoes could not be more dissimilar. This book provides an overview of the history of the discovery (and re-discovery) of the components of the lymphatic system, lymphatic anatomy, physiological functions of lymphatics, molecular features of the lymphatic system, and clinical perspectives involving lymphatics which may be of interest to scientists, clinicians, patients, and the lay public. We provide a current understanding of some of the more important structural similarities and differences between lymphatics and the blood vascular system, their coordinated control by angiogenic and hemangiogenic growth factors and other modulators, the fate and lineage determinants which control lymphatic development, and the roles that lymphatics may play in several different diseases.

Scientists are deciphering the biology of the tumor cell at a level of detail that would have been hard to imagine just a decade or so ago. The development of high-throughput DNA sequencing and genomics technologies have allowed an understanding of the development, growth, survival, and spread of cancer cells in the body. From this information, we now have a basic blueprint or roadmap of how a single damaged cell can develop into a pre-malignant lesion, a primary tumor, and finally, a lethal tumor that may spread throughout the body and resist both medical therapy and host immune responses. In this book, we provide an overview of our current understanding of this cancer blueprint, which has been aided both by the study of familial cancer syndromes, in vitro studies of cancer cells, and animal models. Three classes of genes have emerged from these studies: tumor suppressor genes needed for normal growth control and DNA repair; oncogenes that regulate cell growth and survival, and epigenetic modifiers, enzymes that regulate the modification of DNA and the proteins that form chromatin. Each of these three classes of genes is mutated or altered at least once in virtually all malignant cancer cells. Current technologies permit the DNA sequencing of cancer exomes (coding gene sequencing), whole genomes, transcriptome (all expressed genes), and DNA methylation profiling. These studies show that all tumors have unique constellations of mutated, rearranged, amplified, and deleted genes. Single-cell sequencing further shows that there is extensive variation in individual cells in the tumor; that cancers evolve, and have many of the properties of a multi-cellular entity. Lastly, cancer cells, through mutations in epigenetic modifiers, can reprogram the genome and unlock entire developmental and gene expression pathways to adapt and survive in changing conditions. This reprogramming allows the tumor to elude the host body's defenses, radiotherapy, chemotherapy, and targeted therapy that we use in cancer treatment. Understanding this cancer blueprint paves the way for the development of future therapies to treat and eliminate cancer.

Environmental heat stress is associated with a marked decrease in orthostatic tolerance (OT), which is defined as the ability to stand or sit upright without symptoms of dizziness, lightheadedness, presyncope, or fainting. In most healthy humans, the autonomic nervous system makes rapid and balanced adjustments to heart rate and peripheral blood flow, such that most people are able to stand up "successfully" most of the time, in most environments. The goal of this book is to discuss various aspects of the sympathetic neural response to heat stress, how the sympathetic nervous system coordinates the successful integrative physiological response to orthostasis, and what happens when it encounters both challenges simultaneously. We include overviews of mechanisms of thermoregulation and blood pressure regulation in humans, with particular focus on control of cardiac output and neurovascular control mechanisms during heat stress. We discuss the implications that these changes have for distribution of peripheral blood flow and, in particular, for blood flow to the cerebral circulation. The added stressor of dehydration is also discussed, as it so often goes hand in hand with heat stress. We end with a brief presentation of countermeasures against the decreases in OT with heat stress.

The kidney is innervated with efferent sympathetic nerve fibers reaching the renal vasculature, the tubules, the juxtaglomerular granular cells, and the renal pelvic wall. The renal sensory nerves are mainly found in the renal pelvic wall. Increases in efferent renal sympathetic nerve activity reduce renal blood flow and urinary sodium excretion by activation of 1-adrenoceptors and increase renin secretion rate by activation of 1-adrenoceptors. In response to normal physiological stimulation, changes in efferent renal sympathetic nerve activity contribute importantly to homeostatic regulation of sodium and water balance. The renal mechanosensory nerves are activated by stretch of the renal pelvic tissue produced by increases in renal pelvic tissue of a magnitude that may occur during increased urine flow rate. Under normal conditions, the renal mechanosensory nerves activated by stretch of the sensory nerves elicits an inhibitory renorenal reflex response consisting of decreases in efferent renal sympathetic nerve activity leading to natriuresis. Increasing efferent sympathetic nerve activity increases afferent renal nerve activity which, in turn, decreases efferent renal sympathetic nerve activity by activation of the renorenal reflexes. Thus, activation of the afferent renal nerves buffers changes in efferent renal sympathetic nerve activity in the overall goal of maintaining sodium balance. In pathological conditions of sodium retention, impairment of the inhibitory renorenal reflexes contributes to an inappropriately increased efferent renal sympathetic nerve activity in the presence of sodium retention. In states of renal disease or injury, there is a shift from inhibitory to excitatory reflexes originating in the kidney. Studies in essential hypertensive patients have shown that renal denervation results in long-term reduction in arterial pressure, suggesting an important role for the efferent and afferent renal nerves in hypertension.