Bioethics in Latin America: 1989-1991

In our region, bioethics as an academic discipline and a public movement is still in its beginning stages. The historical changes resulting from scientific and technological advances in biomedicine and from the liberal and pluralist character of industrialized countries have barely begun to occur in the developing countries of Latin America, which remain largely “pretechnical” in their orientation. Bioethics as a secular discipline, with its principles of beneficence, autonomy, and justice, and its emphasis on the rational and free agent in the therapeutic relationship, has not yet reached Latin America.Facultad de Ciencias Médica

A ten-year follow-up of a study of memory for the attack of September 11, 2001: Flashbulb memories and memories for flashbulb events.

Within a week of the attack of September 11, 2001, a consortium of researchers from across the United States distributed a survey asking about the circumstances in which respondents learned of the attack (their flashbulb memories) and the facts about the attack itself (their event memories). Follow-up surveys were distributed 11, 25, and 119 months after the attack. The study, therefore, examines retention of flashbulb memories and event memories at a substantially longer retention interval than any previous study using a test-retest methodology, allowing for the study of such memories over the long term. There was rapid forgetting of both flashbulb and event memories within the first year, but the forgetting curves leveled off after that, not significantly changing even after a 10-year delay. Despite the initial rapid forgetting, confidence remained high throughout the 10-year period. Five putative factors affecting flashbulb memory consistency and event memory accuracy were examined: (a) attention to media, (b) the amount of discussion, (c) residency, (d) personal loss and/or inconvenience, and (e) emotional intensity. After 10 years, none of these factors predicted flashbulb memory consistency; media attention and ensuing conversation predicted event memory accuracy. Inconsistent flashbulb memories were more likely to be repeated rather than corrected over the 10-year period; inaccurate event memories, however, were more likely to be corrected. The findings suggest that even traumatic memories and those implicated in a community's collective identity may be inconsistent over time and these inconsistencies can persist without the corrective force of external influences.This is the author accepted manuscript. The final version is available from the American Psychological Association via http://dx.doi.org/10.1037/xge000005

Long-Term Memory for the Terrorist Attack of September 11: Flashbulb Memories, Event Memories, and the Factors That Influence Their Retention

More than 3,000 individuals from 7 U.S. cities reported on their memories of learning of the terrorist attacks of September 11, as well as details about the attack, 1 week, 11 months, and/or 35 months after the assault. Some studies of flashbulb memories examining long-term retention show slowing in the rate of forgetting after a year, whereas others demonstrate accelerated forgetting. This article indicates that (a) the rate of forgetting for flashbulb memories and event memory (memory for details about the event itself) slows after a year, (b) the strong emotional reactions elicited by flashbulb events are remembered poorly, worse than nonemotional features such as where and from whom one learned of the attack, and (c) the content of flashbulb and event memories stabilizes after a year. The results are discussed in terms of community memory practices.James S. McDonnell FoundationNational Institutes of Health (U.S.) (grant R01- MH0066972

The Critical Juncture Concept’s Evolving Capacity to Explain Policy Change

This article examines the evolution of our understanding of the critical junctures concept. The concept finds its origins in historical intuitionalism, being employed in the context of path dependence to account for sudden and jarring institutional or policy changes. We argue that the concept and the literature surrounding it—now incorporating ideas, discourse, and agency—have gradually become more comprehensive and nuanced as historical institutionalism was followed by ideational historical institutionalism and constructivist and discursive institutionalism. The prime position of contingency has been supplanted by the role of ideas and agency in explaining critical junctures and other instances of less than transformative change. Consequently, the concept is now capable of providing more comprehensive explanations for policy change

Meta-Profiles of Gene Expression during Aging: Limited Similarities between Mouse and Human and an Unexpectedly Decreased Inflammatory Signature

Background: Skin aging is associated with intrinsic processes that compromise the structure of the extracellular matrix while promoting loss of functional and regenerative capacity. These processes are accompanied by a large-scale shift in gene expression, but underlying mechanisms are not understood and conservation of these mechanisms between humans and mice is uncertain. Results: We used genome-wide expression profiling to investigate the aging skin transcriptome. In humans, age-related shifts in gene expression were sex-specific. In females, aging increased expression of transcripts associated with T-cells, B-cells and dendritic cells, and decreased expression of genes in regions with elevated Zeb1, AP-2 and YY1 motif density. In males, however, these effects were contrasting or absent. When age-associated gene expression patterns in human skin were compared to those in tail skin from CB6F1 mice, overall human-mouse correspondence was weak. Moreover, inflammatory gene expression patterns were not induced with aging of mouse tail skin, and well-known aging biomarkers were in fact decreased (e.g., Clec7a, Lyz1 and Lyz2). These unexpected patterns and weak human-mouse correspondence may be due to decreased abundance of antigen presenting cells in mouse tail skin with age. Conclusions: Aging is generally associated with a pro-inflammatory state, but we have identified an exception to this pattern with aging of CB6F1 mouse tail skin. Aging therefore does not uniformly heighten inflammatory status across all mouse tissues. Furthermore, we identified both intercellular and intracellular mechanisms of transcriptome aging, including those that are sex- and species-specific

PI 3 Kinase Related Kinases-Independent Proteolysis of BRCA1 Regulates Rad51 Recruitment during Genotoxic Stress in Human Cells

The function of BRCA1 in response to ionizing radiation, which directly generates DNA double strand breaks, has been extensively characterized. However previous investigations have produced conflicting data on mutagens that initially induce other classes of DNA adducts. Because of the fundamental and clinical importance of understanding BRCA1 function, we sought to rigorously evaluate the role of this tumor suppressor in response to diverse forms of genotoxic stress.We investigated BRCA1 stability and localization in various human cells treated with model mutagens that trigger different DNA damage signaling pathways. We established that, unlike ionizing radiation, either UVC or methylmethanesulfonate (MMS) (generating bulky DNA adducts or alkylated bases respectively) induces a transient downregulation of BRCA1 protein which is neither prevented nor enhanced by inhibition of PIKKs. Moreover, we found that the proteasome mediates early degradation of BRCA1, BARD1, BACH1, and Rad52 implying that critical components of the homologous recombination machinery need to be functionally abrogated as part of the early response to UV or MMS. Significantly, we found that inhibition of BRCA1/BARD1 downregulation is accompanied by the unscheduled recruitment of both proteins to chromatin along with Rad51. Consistently, treatment of cells with MMS engendered complete disassembly of Rad51 from pre-formed ionizing radiation-induced foci. Following the initial phase of BRCA1/BARD1 downregulation, we found that the recovery of these proteins in foci coincides with the formation of RPA and Rad51 foci. This indicates that homologous recombination is reactivated at later stage of the cellular response to MMS, most likely to repair DSBs generated by replication blocks.Taken together our results demonstrate that (i) the stabilities of BRCA1/BARD1 complexes are regulated in a mutagen-specific manner, and (ii) indicate the existence of mechanisms that may be required to prevent the simultaneous recruitment of conflicting signaling pathways to sites of DNA damage