ABSTRACTS: von Hippel-Lindau (VHL) Disease, which was described in the medical literature about a century ago, presents as a hereditary cancer syndrome and is caused by inactivating mutations of the VHL tumor suppressor gene. VHL patients are at high risk for kidney cancers, blood vessel tumors called hemangioblastomas, and neural crest tumors called paragangliomas. VHL mutations, now as acquired mutations rather than inherited mutations, also play important roles in the non-hereditary counterparts of these tumors. VHL-associated tumors often stimulate angiogenesis and red blood cell production due to overproduction of VEGF and erythropoietin, respectively, both of which are normally induced by low oxygen (hypoxia). This was a clue that the VHL protein likely played a role in oxygen sensing. Many hypoxia-inducible genes are regulated by a transcription factor called HIF (hypoxia-inducible factor), which contains an unstable alpha subunit and a stable beta subunit. We and others showed that the VHL protein binds to the HIF alpha subunits and targets them for destruction, but only if the latter have undergone oxygen-dependent hydroxylation of conserved prolyl residues by the EglN family of prolyl hydroxylases. Under low oxygen conditions, EglN activity falls and HIF levels rise. Drugs that inhibit HIF, and particularly HIF2, are now approved to treat sporadic kidney cancer and VHL disease. Conversely, multiple EglN inhibitors, which stabilize HIF, are approved for the treatment of anemia.
ABSTRACTS: Constantin-François Chassebeuf de Boisgirais (1757–1820), known for generations by his pseudonym Volney, was a French revolutionary philosopher, author, traveler, naturalist, historian, teacher, moralist, linguist, and legislator. He was active in momentous political events of what has since become known as the transatlantic Age of Revolutions, and was personally close to many of the giants of the age in the Old World and the New. His life and legacy offer unexplored, unique perspectives on the leaders as well as on the triumphs and the tragedies of the times. But his name, renowned on both sides of the Atlantic during his lifetime and for more than a century beyond, is today unknown to many and is fading in the histories of the age. Through the lens of his life among the giants, his long and intimate relationships with Thomas Jefferson and Napoleon Bonaparte in particular, and his legacy in political and religious philosophy, history, science, literature, art, linguistic scholarship, and more, this essay makes the case that Volney’s name deserves to be refreshed in the histories of his revolutionary age.
ABSTRACTS: Leopard seals ( Hydrurga leptonyx ) are apex predators of the Southern Ocean and exert strong top-down influences on Antarctic food webs. Despite their ecological importance, they remain one of the least studied apex predators due to their solitary behavior and remote distribution across Antarctic and subpolar regions. This research investigates the foraging ecology and reproductive behavior of leopard seals to better understand their ecological role and adaptive strategies in a rapidly changing environment. Using stable isotope analysis of sequentially sampled whiskers from leopard seals at Cape Shirreff, Antarctic Peninsula, we examined individual-level foraging strategies over time. Results indicate that although leopard seals are traditionally considered generalist predators at the population level, most individuals (60%) exhibit strong trophic specialization. Findings highlight the importance of examining predator ecology at the individual level, as a small number of specialized individuals may disproportionately influence prey populations and ecosystem dynamics. In addition to trophic ecology, we present novel observations of leopard seal reproductive behavior from subpolar breeding sites in Chile. Our team documented post-mortem attentive behavior (PAB), where mothers carried and remained with deceased pups for extended periods, in some cases exceeding twenty days. These observations represent one of the longest documented cases of such behavior among mammals and provide rare insight into maternal investment and reproductive strategies in this poorly understood species. Together, these findings emphasize the ecological importance of leopard seals and highlight the need for continued research on their foraging ecology and reproductive biology to better understand their role in Southern Ocean ecosystems.
ABSTRACTS: In this article, Jeffrey Rosen, CEO Emeritus of the National Constitution Center, explores how reading the classical moral philosophy that inspired the Founders changed his life. During COVID, Rosen embarked on an intellectual journey, inspired by Thomas Jefferson’s rigorous reading habits and drawing from Jefferson’s expansive reading list, where he would wake up two hours before sunrise, read moral philosophy, and then watch the sunrise. This exercise led Rosen to understand that happiness meant self-mastery, character improvement, and lifelong learning: being good, not feeling good. Rosen argues that returning to this conception of happiness, which prevailed in ancient times and for much of American history, can teach us how to be a good person, a good citizen, and a champion for civic education in America. By engaging in daily deep reading and learning how to disagree without being disagreeable, we can overcome the growing threats to the American experiment and vindicate the American Idea of liberty, equality, and government by consent.
Abstract: Public discourse and dramatic news headlines are rife with sweeping claims about technology’s impact on youth mental health but are often missing youth voices. Teen-level insights about growing up with digital technologies reveal known challenges as well as subtle pressures and hidden sources of positivity behind teens’ screens. Listening-centered approaches help us see meaningful variation among youth in their tech-related experiences and point toward solutions that go beyond abstinence to support agency.
Abstract: Many plants rely on fruit-eating animals to disperse. The world’s smallest primates, the mouse lemurs, can effectively disperse seeds in Madagascar’s rainforests. Since they can live and move through human-modified landscapes, my research examines how they perform such ecological roles along different habitat disturbance levels. I found that these tiny animals are full of surprise: they are resilient to cyclones and forest degradation; they are able to maintain their population size at the expense of their body conditions; and they can travel far and fast in the rainforest. Such discoveries are good news for them because they can escape unfavorable areas to better thrive and they can take the seeds away from their parents, promoting their regeneration and that of the forest.
Abstract: The human capacity to build ideas is the single most powerful and distinctive feature of our evolution as a species. And yet, we know little about how this capacity emerges. When do children begin constructing ideas, and how does this complex and impressive process unfold? I describe research examining the emergence and early development of the two pillars of idea-building: curiosity and invention. I also offer evidence that at a surprisingly early age children are drawn to considering complex and weighty ideas, such as death and the origins of the human existence. The ability and disposition to consider ideas, so vibrant and robust in early childhood, are easily discouraged as children grow older. The paper ends with a discussion of why it is so important to foster rather than inhibit children’s ability to develop ideas and suggests future directions for research and applications.
Abstract: Discusses current realities of advances with ECMO (Extra Corporeal Membrane Oxygenation) and hypothermic circulatory arrest (HCA), extracorporeal membrane oxygenation devices, though nomenclature and use differentiates the various systems. "Cardiopulmonary bypass" is a means of diverting blood flow that is returning to the heart and avoiding the heart and the lungs. This process is used during heart surgery and allows for a still operative field for the surgeon. Cardiopulmonary bypass is typically used for people who are having coronary artery bypass grafting or heart valve replacement
Abstract: DARPA was initially founded as the ARPA (Advanced Research Projects Agency) in 1958 in response to the Soviet Union's launch of Sputnik. The goal was to never be subject to that sort of strategic surprise ever again. But DARPA also wanted to spearhead its research and development agency, which was really pushing the United States to be on the bleeding edge of technology. To do this, DARPA has a unique formula: embrace high-risk, high-reward projects to support the DoD (Department of Defense). This formula deals with the people, the culture, and the processes. DARPA program managers are really responsible for conceiving and managing the programs throughout their life cycle. But our programs are somewhat different from National Institutes of Health or National Science Foundation grants; they're really metrics based on and bound to the shore of success.
