The retrotransposon Long Interspersed Element 1 (LINE‐1 or L1) has played a major role in shaping the sequence composition of the mammalian genome. In our recent publication, “Heritable L1 retrotransposition in the mouse primordial germline and early embryo,” we systematically assessed the rate and developmental timing of de novo, heritable endogenous L1 insertions in mice. Such heritable retrotransposition events allow L1 to exert an ongoing influence upon genome evolution. Here, we place our findings in the context of earlier studies, and (...) highlight how our results corroborate, and depart from, previous research based on human patient samples and transgenic mouse models harboring engineered L1 reporter genes. In parallel, we outline outstanding questions regarding the stage‐specificity, regulation, and functional impact of embryonic and germline L1 retrotransposition, and propose avenues for future research in this field. -/- . (shrink)

Gene retrocopies are generated by reverse transcription and genomic integration of mRNA. As such, retrocopies present an important exception to the central dogma of molecular biology, and have substantially impacted the functional landscape of the metazoan genome. While an estimated 8,000–17,000 retrocopies exist in the human genome reference sequence, the extent of variation between individuals in terms of retrocopy content has remained largely unexplored. Three recent studies by Abyzov et al., Ewing et al. and Schrider et al. have exploited 1,000 (...) Genomes Project Consortium data, as well as other sources of whole‐genome sequencing data, to uncover novel gene retrocopies. Here, we compare the methods and results of these three studies, highlight the impact of retrocopies in human diversity and genome evolution, and speculate on the potential for somatic gene retrocopies to impact cancer etiology and genetic diversity among individual neurons in the mammalian brain. (shrink)

This book taps the best American thinkers to answer the essential American question: How do we sustain our experiment in government of, by, and for the people? Authored by an extraordinary and politically diverse roster of public officials, scholars, and educators, these chapters describe our nation's civic education problem, assess its causes, offer an agenda for reform, and explain the high stakes at risk if we fail.

This book assesses how Vatican II opened up the Catholic Church to encounter, dialogue, and engagement with other world religions. Opening with a contribution from the President of the Pontifical Council for Interreligious Dialogue, Cardinal Jean-Louis Tauran, it next explores the impact, relevance, and promise of the Declaration Nostra Aetate before turning to consider how Vatican II in general has influenced interfaith dialogue and the intellectual and comparative study of world religions in the postconciliar decades, as well as the contribution (...) of particular past and present thinkers to the formation of current interreligious and comparative theological methods. Additionally, chapters consider interreligious dialogue vis-à-vis theological anthropology in conciliar documents; openness to the spiritual practices of other faith traditions as a way of encouraging positive interreligious encounter; the role of lay and new ecclesial movements in interreligious dialogue; and the development of Monastic Interreligious Dialogue. Finally, it includes a range of perspectives on the fruits and future of Vatican’s II’s opening to particular faiths such as Judaism, Islam, Hinduism, and Buddhism. (shrink)

In this consensus report by a diverse group of academics who conduct and/or are concerned about social and behavioral genomics (SBG) research, the authors recount the often‐ugly history of scientific attempts to understand the genetic contributions to human behaviors and social outcomes. They then describe what the current science—including genomewide association studies and polygenic indexes—can and cannot tell us, as well as its risks and potential benefits. They conclude with a discussion of responsible behavior in the context of SBG research. (...) SBG research that compares individuals within a group according to a “sensitive” phenotype requires extra attention to responsible conduct and to responsible communication about the research and its findings. SBG research (1) on sensitive phenotypes that (2) compares two or more groups defined by (a) race, (b) ethnicity, or (c) genetic ancestry (where genetic ancestry could easily be misunderstood as race or ethnicity) requires a compelling justification to be conducted, funded, or published. All authors agree that this justification at least requires a convincing argument that a study's design could yield scientifically valid results; some authors would additionally require the study to have a socially favorable risk‐benefit profile. (shrink)

Background: Clinical genomic implementation studies pose challenges for informed consent. Consent forms often include complex language and concepts, which can be a barrier to diverse enrollment, and these studies often blur traditional research-clinical boundaries. There is a move toward self-directed, web-based research enrollment, but more evidence is needed about how these enrollment approaches work in practice. In this study, we developed and evaluated a literacy-focused, web-based consent approach to support enrollment of diverse participants in an ongoing clinical genomic implementation study. (...) Methods: As part of the Cancer Health Assessments Reaching Many (CHARM) study, we developed a web-based consent approach that featured plain language, multimedia, and separate descriptions of clinical care and research activities. CHARM offered clinical exome sequencing to individuals at high risk of hereditary cancer. We interviewed CHARM participants about their reactions to the consent approach. We audio recorded, transcribed, and coded interviews using a deductively and inductively derived codebook. We reviewed coded excerpts as a team to identify overarching themes. Results: We conducted 32 interviews, including 12 (38%) in Spanish. Most (69%) enrolled without assistance from study staff, usually on a mobile phone. Those who completed enrollment in one day spent an average of 12 minutes on the consent portion. Interviewees found the information simple to read but comprehensive, were neutral to positive about the multimedia support, and identified increased access to testing in the study as the key difference from clinical care. Conclusions: This study showed that interviewees found our literacy-focused, web-based consent approach acceptable; did not distinguish the consent materials from other online study processes; and valued getting access to testing in the study. Overall, conducting empirical bioethics research in an ongoing clinical trial was useful to demonstrate the acceptability of our novel consent approach but posed practical challenges. (shrink)

The dorsal anterior cingulate cortex is a key node in the human salience network. It has been ascribed motor, pain-processing and affective functions. However, the dynamics of information flow in this complex region and how it responds to inputs remain unclear and are difficult to study using non-invasive electrophysiology. The area is targeted by neurosurgery to treat neuropathic pain. During deep brain stimulation surgery, we recorded local field potentials from this region in humans during a decision-making task requiring motor output. (...) We investigated the spatial and temporal distribution of information flow within the dACC. We demonstrate the existence of a distributed network within the anterior cingulate cortex where discrete nodes demonstrate directed communication following inputs. We show that this network anticipates and responds to the valence of feedback to actions. We further show that these network dynamics adapt following learning. Our results provide evidence for the integration of learning and the response to feedback in a key cognitive region. (shrink)

Bioethics at the Movies explores the ways in which popular films engage basic bioethical concepts and concerns. Twenty philosophically grounded essays use cinematic tools such as character and plot development, scene-setting, and narrative-framing to demonstrate a range of principles and topics in contemporary medical ethics. The first section plumbs popular and bioethical thought on birth, abortion, genetic selection, and personhood through several films, including The Cider House Rules, Citizen Ruth, Gattaca, and I, Robot. In the second section, the contributors examine (...) medical practice and troubling questions about the quality and commodification of life by way of Dirty Pretty Things, Eternal Sunshine of the Spotless Mind, and other movies. The third section's essays use Million Dollar Baby, Critical Care, Big Fish, and Soylent Green to show how the medical profession and society at large view issues related to aging, death, and dying. A final section makes use of Extreme Measures and select Spanish and Japanese films to discuss two foundational matters in bioethics: the role of theories and principles in medicine and the importance of cultural context in devising care. Structured to mirror bioethics and cinema classes, this innovative work includes end-of-chapter questions for further consideration and contributions from scholars from the United States, Canada, the United Kingdom, Israel, Spain, and Australia. Contributors: Robert Arp, Ph.D., Michael C. Brannigan, Ph.D., Matthew Burstein, Ph.D., Antonio Casado da Rocha, Ph.D., Stephen Coleman, Ph.D., Jason T. Eberl, Ph.D., Paul J. Ford, Ph.D., Helen Frowe, M.A., Colin Gavaghan, Ph.D., Richard Hanley, Ph.D., Nancy Hansen, Ph.D., Al-Yasha Ilhaam, Ph.D., Troy Jollimore, Ph.D., Amy Kind, Ph.D., Zana Marie Lutfiyya, Ph.D., Terrance McConnell, Ph.D., Andy Miah, Ph.D., Nathan Norbis, Ph.D., Kenneth Richman, Ph.D., Karen D. Schwartz, LL.B., M.A., Sandra Shapshay, Ph.D., Daniel Sperling, LL.M., S.J.D., Becky Cox White, R.N., Ph.D., Clark Wolf, Ph.D. (shrink)

This study examines the leading early nineteenth-century Scottish moral philosopher Dugald Stewart’s discussion of the origin and development of religion. Stewart developed his account in his final work, The Philosophy of the Active and Moral Powers of Man (1828), in an effort to show that the fact that polytheism was the first religion of humankind does not undermine the truth of monotheism. He wrote in response to similar discussions presented in David Hume’s “Natural History of Religion” (1757), which argued for (...) the primacy of polytheism, and Stewart’s old moral philosophy tutor Adam Ferguson’s Principles of Moral and Political Science (1792), which argued for the primacy of monotheism. Stewart accepted the conclusions of the Scots’ enlightened study of religion, which argued for truth of Hume’s account, but aimed to reassert many of the natural theological arguments about the naturalness of religion that the “Natural History” had challenged. Stewart’s discussion acts as a useful way by which we can assess the achievement of the literati’s study of religion. (shrink)

The Plasmodium falciparum genome‐sequencing project has provided malariologists with vast amounts of new information pertinent to a multitude of cellular processes that previously were only guessed about. In exploring this morass of predicted genes and proteins, there is now a danger of simply re‐inventing the cell. Fortunately, new global transcriptional analyses reassure malariologists that they are not dealing with just “any old cell.” The informative papers on the plasmodial transcriptome by Le Roch et al. (2003)1 and Bozdech et al. (2003)2 (...) discussed below forge a bridge between the genomics and proteomics of P. falciparum. They are likely to act as a fulcrum upon which much future research will turn: for example, the study of regulation and feed‐back loops. BioEssays 26:339–342, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Forbidden areas, i.e. areas (sites, cities, countries) that are inaccessible for topographical reasons or especially because of decisions based on political, religious, or other motivations are usually surrounded by an aura of mystery and almost necessarily arouse curiosity. The dream of generations of explorers was to reach Lhasa. An area can be closed not only to outsiders but also to “insiders:” nobody is allowed to leave for the “outside.” The isolation imposed on Japan by the Tokugawa regime was such a (...) two-way seclusion aided, of course, by geographical conditions and hence easily enforceable. It has been suggested, perhaps not quite seriously, that the famous Chinese wall was meant not only to keep out barbarian invaders, but also to prevent Chinese from leaving. That there was some kind of border control is also suggested by the leger, according to which Lao-tse, before disappearing into the west, committed his teaching, the Tao-te-kinq, to writing at the request of the “gatekeeper.” One may well wonder whether there exists another equally influential text written at the behest of a border policeman! (shrink)

Routledge is now re-issuing this prestigious series of 204 volumes originally published between 1910 and 1965. The titles include works by key figures such asC.G. Jung, Sigmund Freud, Jean Piaget, Otto Rank, James Hillman, Erich Fromm, Karen Horney and Susan Isaacs. Each volume is available on its own, as part of a themed mini-set, or as part of a specially-priced 204-volume set. A brochure listing each title in the "International Library of Psychology" series is available upon request.