Differential roles of resistance to proactive interference and suppression of prepotent responses in overgeneral memory.

BACKGROUND AND OBJECTIVES: Overgeneral memory (OGM), difficulty in retrieving specific autobiographical memories, is a robust phenomenon related to the onset and course of depressive and posttraumatic stress disorders. Inhibitory mechanisms are theorized to underlie OGM; however, empirical support for this link is equivocal. The current study examines the differential roles of two aspects of inhibitory control in association with OGM: suppression of prepotent responses and resistance to proactive interference (PI). Only resistance to PI was expected to be negatively related to OGM, whereby individuals with greater ability to resist PI would have reduced OGM. METHOD: Participants (n = 49) completed a self-report measure of depressive symptoms and engaged in two tasks aimed at assessing resistance to PI and suppression of prepotent responses. Participants also completed a task assessing overgeneral autobiographical memory. RESULTS: As hypothesized, resistance to PI, but not suppression of prepotent responses negatively predicted OGM above and beyond the influence of depressive symptoms. LIMITATIONS: Because a double dissociation was not examined, we cannot address the potential independence of the submechanisms of inhibitory control that we assessed. CONCLUSIONS: Results exemplify the differential associations of two components of inhibition and OGM, suggesting that resistance to PI, in particular, may contribute to the development and/or maintenance of OGM and associated depressive disorders. Directions for future research are discussed.

Minireview: Endocrine Disruptors: Past Lessons and Future Directions.

Within the past few decades, the concept of endocrine-disrupting chemicals (EDCs) has risen from a position of total obscurity to become a focus of dialogue, debate, and concern among scientists, physicians, regulators, and the public. The emergence and development of this field of study has not always followed a smooth path, and researchers continue to wrestle with questions about the low-dose effects and nonmonotonic dose responses seen with EDCs, their biological mechanisms of action, the true pervasiveness of these chemicals in our environment and in our bodies, and the extent of their effects on human and wildlife health. This review chronicles the development of the unique, multidisciplinary field of endocrine disruption, highlighting what we have learned about the threat of EDCs and lessons that could be relevant to other fields. It also offers perspectives on the future of the field and opportunities to better protect human health.

A new approach to synergize academic and guideline-compliant research: the CLARITY-BPA research program.

Recently, medical research has seen a strong push toward translational research, or "bench to bedside" collaborations, that strive to enhance the utility of laboratory science for improving medical treatment. The success of that paradigm supports the potential application of the process to other fields, such as risk assessment. Close collaboration among academic, government, and industry scientists may enhance the translation of scientific findings to regulatory decision making. The National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS), and U.S. Food and Drug Administration (FDA) developed a consortium-based research program to link more effectively academic and guideline-compliant research. An initial proof-of-concept collaboration, the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA), uses bisphenol A (BPA) as a test chemical. The CLARITY-BPA program combines a core perinatal guideline-compliant 2-year chronic toxicity study with mechanistic studies/endpoints conducted by academic investigators. Twelve extramural grantees were selected by NIEHS through an RFA-based initiative to participate in the overall study design and conduct disease-relevant investigations using tissues and animals from the core study. While the study is expected to contribute to our understanding of potential effects of BPA, it also has ramifications beyond this specific focus. Through CLARITY-BPA, NIEHS has established an unprecedented level of collaboration among extramural grantees and regulatory researchers. By drawing upon the strengths of academic and regulatory expertise and research approaches, CLARITY-BPA represents a potential new model for filling knowledge gaps, enhancing quality control, informing chemical risk assessment, and identifying new methods or endpoints for regulatory hazard assessments.

ONE Nano: NIEHS's strategic initiative on the health and safety effects of engineered nanomaterials.

BACKGROUND: The past decade has seen tremendous expansion in the production and application of engineered nanomaterials (ENMs). The unique properties that make ENMs useful in the marketplace also make their interactions with biological systems difficult to anticipate and critically important to explore. Currently, little is known about the health effects of human exposure to these materials. OBJECTIVES: As part of its role in supporting the National Nanotechnology Initiative, the National Institute of Environmental Health Sciences (NIEHS) has developed an integrated, strategic research program-"ONE Nano"-to increase our fundamental understanding of how ENMs interact with living systems, to develop predictive models for quantifying ENM exposure and assessing ENM health impacts, and to guide the design of second-generation ENMs to minimize adverse health effects. DISCUSSION: The NIEHS's research investments in ENM health and safety include extramural grants and grantee consortia, intramural research activities, and toxicological studies being conducted by the National Toxicology Program (NTP). These efforts have enhanced collaboration within the nanotechnology research community and produced toxicological profiles for selected ENMs, as well as improved methods and protocols for conducting in vitro and in vivo studies to assess ENM health effects. CONCLUSION: By drawing upon the strengths of the NIEHS's intramural, extramural, and NTP programs and establishing productive partnerships with other institutes and agencies across the federal government, the NIEHS's strategic ONE Nano program is working toward new advances to improve our understanding of the health impacts of engineered nanomaterials and support the goals of the National Nanotechnology Initiative.

Consortium-based science: the NIEHS's multipronged, collaborative approach to assessing the health effects of bisphenol A.

BACKGROUND: Bisphenol A (BPA) is a high production volume chemical used to make polycarbonate plastic and is found in many consumer products. Some studies using animal models have suggested that BPA exposures may have adverse health effects. However, research gaps have precluded a full understanding of the effects of BPA in humans and engendered controversies surrounding the chemical's potential toxicity. OBJECTIVES: The National Institute of Environmental Health Sciences (NIEHS) and National Toxicology Program (NTP) have developed an integrated, multipronged, consortium-based approach to optimize BPA-focused research investments to more effectively address data gaps and inform decision making. DISCUSSION: NIEHS/NTP BPA research investments made over the past 4 years include extramural research grants, establishment of a BPA Grantee Consortium, intramural research activities on BPA's mechanisms of action, the launch of two clinical studies and an occupational study, development of a round-robin experiment to validate BPA measurements in human serum, and, in collaboration with the Food and Drug Administration (FDA), formation of a consortium to design and execute a chronic toxicity study of BPA in rats. The NIEHS's new consortium-based approach has led to more integrated, collaborative efforts and should improve our ability to resolve controversies over the potential human health effects of exposures to low levels of endocrine-active agents.