Sharp boundaries of Dpp signalling trigger local cell death required for Drosophila leg morphogenesis

Article available at http://dx.doi.org/10.1038/ncb1518Morphogens are secreted signalling molecules that govern many developmental processes1. In the Drosophila wing disc, the transforming growth factor (TGF) homologue Decapentaplegic (Dpp) forms a smooth gradient and specifies cell fate by conferring a defined value of morphogen activity. Thus, neighbouring cells have similar amounts of Dpp protein, and if a sharp discontinuity in Dpp activity is generated between these cells, Jun kinase (JNK)-dependent apoptosis is triggered to restore graded positional information2, 3. To date, it has been assumed that this apoptotic process is only activated when normal signalling is distorted. However, we now show that a similar process occurs during normal development: rupture in Dpp activity occurs during normal segmentation of the distal legs of Drosophila. This sharp boundary of Dpp signalling, independently of the absolute level of Dpp activity, induces a JNK—reaper-dependent apoptosis required for the morphogenesis of a particular structure of the leg, the joint. Our results show that Dpp could induce a developmental programme not only in a concentration dependent manner, but also by the creation of a sharp boundary of Dpp activity. Furthermore, the same process could be used either to restore a normal pattern in response to artificial disturbance or to direct a morphogenetic process.This work has been supported by grants from the Dirección General de Investigación Científica y Técnica (BMC 2002-00300), the Comunidad Autónoma de Madrid (08.1/0031/2001.1 and GR/SAL/0147/2004) and an Institutional Grant from the Fundación Ramón Areces. C.M. is a recipient of a Formación del Personal Universitario (F.P.U.) fellowship from the Ministerio de Educación y Ciencia.Peer reviewe

Anhydrobiosis-Associated Nuclear DNA Damage and Repair in the Sleeping Chironomid: Linkage with Radioresistance

Anhydrobiotic chironomid larvae can withstand prolonged complete desiccation as well as other external stresses including ionizing radiation. To understand the cross-tolerance mechanism, we have analyzed the structural changes in the nuclear DNA using transmission electron microscopy and DNA comet assays in relation to anhydrobiosis and radiation. We found that dehydration causes alterations in chromatin structure and a severe fragmentation of nuclear DNA in the cells of the larvae despite successful anhydrobiosis. Furthermore, while the larvae had restored physiological activity within an hour following rehydration, nuclear DNA restoration typically took 72 to 96 h. The DNA fragmentation level and the recovery of DNA integrity in the rehydrated larvae after anhydrobiosis were similar to those of hydrated larvae irradiated with 70 Gy of high-linear energy transfer (LET) ions (4He). In contrast, low-LET radiation (gamma-rays) of the same dose caused less initial damage to the larvae, and DNA was completely repaired within within 24 h. The expression of genes encoding the DNA repair enzymes occurred upon entering anhydrobiosis and exposure to high- and low-LET radiations, indicative of DNA damage that includes double-strand breaks and their subsequent repair. The expression of antioxidant enzymes-coding genes was also elevated in the anhydrobiotic and the gamma-ray-irradiated larvae that probably functions to reduce the negative effect of reactive oxygen species upon exposure to these stresses. Indeed the mature antioxidant proteins accumulated in the dry larvae and the total activity of antioxidants increased by a 3–4 fold in association with anhydrobiosis. We conclude that one of the factors explaining the relationship between radioresistance and the ability to undergo anhydrobiosis in the sleeping chironomid could be an adaptation to desiccation-inflicted nuclear DNA damage. There were also similarities in the molecular response of the larvae to damage caused by desiccation and ionizing radiation

History, Nonviolence, and the Experience of Values

AN ABSTRACT OF THE DISSERTATION OF Anthony Cashio, for the Doctor of Philosophy degree in Philosophy, presented on February 25, 2011, at Southern Illinois University Carbondale. TITLE: History, Nonviolence, and the Experience of Values MAJOR PROFESSOR: Dr. Randall E. Auxier The goal of this dissertation is to address the question: what are values? To carry out this inquiry in a manner which will provide new insights into the complexity, difficulty, and importance of this question, I propose to look to actual historical events, specifically the event known as the Children\u27s Movement that took place in Birmingham, Alabama on March 3, 1963. Coupling this historical approach with an analysis and exploration of the philosophies of nonviolence, specifically the works of Mohandas K. Gandhi and Martin Luther King, Jr., will allow for answers to age-old axiological problems that are grounded in both pure theory and praxis of shared communal experience. I submit that one of the main lessons learned through this inquiry into the experience of values is that what is truly experienced in the liminal moment of the successful nonviolent protest is what I name a lived value-system. This lived value-system is characterized by the attempt in every moment to bring the culturally learned value-system, the values which we are taught are integral to a society, into resonance with the ideal value-system, the value-system of dogmatic objective certitude. The task of fleshing out these three value-systems in response to an understanding of history as a starting point for philosophical inquiry is the primary task of this dissertation

Towards a Cure for Lunacy

Preview: /Review: Katarzyna Kremplewska, Life as Insinuation: George Santayana’s Hermeneutics of Finite Life and Human Self (Albany: State University of New York Press, 2019), 269 pages./ George Santayana was a man in-between. He worked in-between philosophy, literature, and cultural criticism. He lived in-between American and European cultures. While he has always held a unique place in the history of American thought and philosophy he spent the last portion of his life in Europe seeking to “cultivate imagination, love it, give it endless forms.” He was concerned with how to live and to teach others how to live a life of sincere contemplation and enjoyment that elevates and celebrates the best of what it means to be a human being. He also worked to bridge the gap between the animal and the sublime in order to cure the brutalism and lunacy he witnessed settling into American and European cultures. Katarzyna Kremplewska’s deep, deft, and welcome addition to Santayana scholarship, Life as Insinuation: George Santayana’s Hermeneutics of Finite Life and Human Self (from here on referred to as LI), draws upon this in-betweenness of his life and work to explore the conception of the self and to bring Santayana into conversation with some of the twentieth century’s most important philosophers. As Kremplewska summarizes her own work, “I am tracing the connections in-between different areas of Santayana’s philosophical engagement – from his ontology through literary criticism to his critique of culture – while striving to bring to light its hermeneutic coherence, corresponding to the idea of a hermeneutic of life” (LI, xi)