Frederick Davis - US grants

DESCRIPTION ( applicant's abstract): The disruption of sleep is a widespread problem among children and is one of the most common concerns parents have about their children's behavior. Sleep problems early in life tend to persist into older ages, and sleep disorders can be severe in children with neurological or psychiatric pathologies. Sleep is controlled by two processes, a homeostatic process and a circadian pacemaker. Entrainment of the circadian pacemaker is responsible for the appropriate timing of sleep and wakefulness relative to the environment. The development of a normal sleep/wake cycle requires the development and entrainment of the circadian pacemaker. Previous work of this project has shown in hamsters that the pacemaker begins before birth and is entrained by rhythmicity of the mother. Similar timing in humans would mean that the fetal pacemaker is functioning and is influenced by maternal rhythms throughout most of gestation. The goal of the proposed project is to better understand the physiology of the fetal pacemaker and understand how it is influenced by maternal rhythms, including the long-term consequences of abnormal entrainment. By measuring recently discovered molecular components of the pacemaker, we will test hypotheses about the similarities and differences between the developing and mature pacemaker and about the regulation of these molecules during development. We will specifically examine the physiological significance of maternal melatonin and the long-term effects of maternal entrainment. The project will better our understanding of fetal pacemaker regulation and the importance of the environment under which it develops.

The behavior and physiology of animals and humans are regulated by endogenously generated 24-hour (circadian) rhythms. The suprachiasmatic nucleus (SCN) of the hypothalamus contains a circadian pacemaker that is essential for the regulation of circadian rhythms. Disruptions of circadian rhythms affect the health and well-being of millions of people and result from external disturbances such as shift-work and jet-lag and from constitutional variation of known (e.g. blindness) and unknown causes. A possible source of variation is the environment during development. The proposed project will study the development of circadian rhythms and the development of the SCN in an established animal model for circadian rhythms research, the hamster. The long-term goals of the project are: l. To understand the relationship between SCN organization and the regulation of circadian rhythms by examining this relationship during development, 2. To understand the mechanisms by which maternal physiology influences the fetal circadian pacemaker, and 3. To identify aspects of SCN development that might be subject to modification and therefore lead to long-term disruption of circadian regulation. The Specific Aims are to test hypotheses in four critical areas: l. The role of the pineal gland hormone melatonin in the development of the mammalian circadian pacemaker, 2. The role of a specific fetal neurotransmitter system (dopamine) in the development of the circadian pacemaker; 3. The prenatal development of the SCN at the time pacemaker function begins, and 4. The postnatal development of the SCN at the time neural connections from the eyes are formed. The functional development of the pacemaker will be assessed by measuring behavioral rhythms of young hamsters and of hamsters that have received grafts of the fetal SCN. The development of the SCN will be examined with anatomical methods that include immunohistochemistry, in situ hybridization, and receptor binding assays. A unique strain of hamsters with a mutation that affects circadian rhythms will also be used. Knowledge of SCN development is essential to understand the normal as well as abnormal regulation of circadian rhythms. In addition, maternal influence on the development of fetal circadian rhythms via a dopaminergic system indicates that drugs of abuse (e.g., cocaine) can affect the development of circadian rhythms.

DESCRIPTION (provided by applicant): The long-term goal of the project is to identify signals that mediate the circadian regulation of behavior. Twenty-four hour (circadian) rhythms are strongly expressed in the behavior of animals and humans. For example, the homeostatic regulation of sleep is modulated by circadian output so that sleep is consolidated and phased to occur at a particular time of day. A circadian pacemaker in the hypothalamus, the suprachiasmatic nucleus (SCN), drives the circadian modulation of sleep as well as rhythms in other behaviors and in neuroendocrine and metabolic functions. The phasing of these rhythms is regulated by light via entrainment of the SCN and retinal projections that are distinct from the visual system. Non-visual projections also mediate acute effects of light on behavior and neuroendocrine function. Little is known about the output mechanisms for the circadian regulation of behavior or for the acute, non-visual effects of light. SCN transplant experiments show that an SCN signal can affect downstream targets for the control of activity by diffusion from the third ventricle. Previously, we infused candidate molecules into the third ventricle of hamsters, and found that an SCN peptide, transforming growth factor alpha (TGFalpha) strongly inhibits wheel-running activity. TGF-alpha could mediate both the acute effects of light on behavior as well as the circadian modulation of behavior. In this project we will test two hypotheses: 1. That TGFalpha is a physiologically important output signal of the SCN, and 2. That a specific hypothalamic structure, the subparaventricular zone, is an essential target for SCN output and the acute effects of light. In addition, the same methods used to identify TGFalpha will be used to evaluate the role of other SCN peptides as output signals. An understanding of SCN output may allow the development of therapies for the treatment of abnormal sleep timing and consolidation. In addition, identifying mechanisms for the acute effects of light may lead to a better understanding of light therapy that is commonly used to treat mood disorders.

Archie Carr and the Conservation of Sea Turtles: 1937-1987
Frederick R. Davis
Florida State University
Project Summary
The proposed project is the first biography of Archie Carr (1909-1987), who was one of
the most revered twentieth-century naturalists, the world's authority on sea turtles throughout much of his career, and a central figure in the development of conservation biology as a scientific study. The intellectual merit of my study of Archie Carr is that it examines a remarkable scientist who led the campaign for the conservation of sea turtles around the world. Carr's story is compelling for three reasons. First, his study of turtles and herpetology spanned five decades (1937-1987) and his work reflected major shifts in the study of ecology and evolution in America across that period. Second, Carr was a nature writer, par excellence, and his stories made accessible the natural history of sea turtles and the culture of places they lived. Finally, more than any other individual, Carr was responsible for the international conservation of sea turtles of all species. As a biographical study of a naturalist of the twentieth century, this study will link Paul
Farber's notion of the "naturalist tradition" to Thomas Soderqvist's provocative reification of the role of biography in the history of science. In addition to the two primary goals, this project will analyze narratives of science and conservation to bridge the gap between environmental history and the history of biology by demonstrating the significance of the naturalist tradition to the rise of environmentalism in America.
In terms of broader impacts, my study employs Carr's life and work as a lens through
which to explore trends in the history of biology and important links to environmental history. Through Carr I will consider issues in which he played a crucial role during his long career, particularly the continued evolution of the naturalist tradition and the emergence of the activist scientist in the twentieth century. In addition to Carr's scientific research, his teaching, writing, and activism influenced a wide audience both within and beyond academia. In a similar vein, his biography has the potential to inspire current educators, nature writers, and conservationists. Sea turtles and their protection continue to fascinate scientists and lay people alike. Beyond the research outlined here, I address all of these issues in a new course I designed for undergraduates and graduate students called, "Florida Environmental History" and while directing and serving
on graduate committees.

Two distinct groups of scholars engage in the process of building scientific knowledge: scientists and the humanists who study science (philosophers, historians, etc.). Despite potential synergy among these groups of scholars, the most fundamental disciplinary rift in modern academic training is between the sciences and the humanities. Science and the humanities differ not just in professional language, but also in their very cultures and modes of communication (e.g., style of writing, publication format, conventions of oral presentation). These differences present barriers to communication and collaboration that are detrimental to progress in each of these fields.

Intellectual merit. The objective of the proposed program in the History and Philosophy of Biology is to bring together historians and philosophers of biology with biologists studying ecology and evolutionary biology. Interdisciplinary teams of graduate students, a postdoctoral fellow, and faculty mentors will engage in original research in the history or philosophy of ecology and evolutionary biology. Graduate students and postdocs will also participate in courses, workshops and seminars that involve faculty and students from all departments. Outcomes of interdisciplinary research will include publishable papers, presentations at local and national meetings, and graduate students with an unusual breadth of training. Graduates of this program will have the tools to allow them to conduct stronger research in their own fields, be better educators and communicators, and act as leaders in collaborations between the various disciplines that study science. Further, this education and research program will serve as a starting point for a permanent interdisciplinary program for graduate students across History, Philosophy, and Biology at Florida State University. This will build upon an existing foundation of interactions between a recently established History and Philosophy of Science Program and the long-standing Ecology and Evolutionary Biology graduate program at Florida State University.

Broader Impacts. Through this fellowship program, nine graduate fellows and three postdoctoral fellows will receive training in research methods within and outside their disciplines. Through collaborative research and coursework, these fellows will gain a broader perspective on their own fields. This will produce students who will be leaders in future collaborative research, and teachers who can train the next generation of students to work across the science/humanities boundary. By focusing student attentions on the history and philosophy of ecology and evolutionary biology, the proposed program will also encourage research into the nature of the science at the heart of important current policy issues such as global warming, transgenic organisms, and the teaching of evolution. We foresee this program continuing as a permanent program at Florida State University. An improved understanding of the nature of these sciences will facilitate effective communication of the findings of these sciences to the public and to policy makers. Finally, there will be aggressive recruitment of excellent graduate student and postdoctoral fellows from among underrepresented groups, increasing diversity in our graduate and postdoctoral populations.

[unreadable] DESCRIPTION (provided by applicant): [unreadable] [unreadable] Pesticides and Toxicology: A Century of Environmental Health is the first detailed historical examination of the development of the art and science of environmental risk assessment. This study reveals how health scientists, industry scientists, science writers, government regulators and legislators responded to threats to environmental health throughout the twentieth century. At several key nodes during the twentieth century, scientists and popular science writers united to inspire protective legislation. Each of these episodes revealed rapid increase in new chemicals, toxicological methodologies, popular awareness, and legislative activity. While the chemical industry continued to generate literally thousands of new chemicals, particularly insecticides, scientists and legislators struggled to respond with appropriate safety standards. The development of the chemicals continues to proceed faster than the methods of analysis and regulation. Such challenges gave rise to the evolution of environmental risk assessment, which has become the dominant paradigm in the analysis of environmental quality and health. [unreadable] [unreadable] My research seeks to answer several key questions: How did the methodologies of toxicology evolve alongside the development and widespread use of new chemical insecticides? How did toxicology coalesce into formal academic programs, a society, and a discipline? How did science writers depict threats to environmental health in ways that raised popular awareness and legislative concern? How did corporations, represented by the chemical and pesticides trade organizations, attempt to address (or dismiss) the concerns of consumers and their representatives? What was the role of the new study of toxicology in Rachel Carson's Silent Spring? How did government regulators and legislators employ toxicology in the development of policies regarding pesticides? Finally, how did environmental risk assessment draw on the methodologies of toxicology? Thus, in answering these questions, Pesticides and Toxicology provides insights into the evolution of environmental health and its many facets: the institutions, corporations, government organizations, as well as popular perceptions of toxicology, environmental risk assessment, and environmental health policy. Project Narrative Pesticides and Toxicology: A Century of Environmental Health has considerable significance to public health in that it will explore the foundations of the closely related discipline of environmental health. This is a story that will appeal to historians of public health, medicine, and science. Beyond the expected academic readership, this study should interest the wider community of people who wish to understand the role of pesticides, toxicology, and environmental risk assessment in the evolution of environmental health, activism, and policy. [unreadable] [unreadable]

Oxygen is an important element in Earth's mantle and makes up the bulk of most rocks. Its chemical activity (i.e. fugacity) is a controlling factor in determining: (1) the composition of magmas that form from mantle melting, (2) the minerals that are present and in equilibrium with one another in a rock, (3) the distribution of chemical species in associated magmatic fluids, and (4) the partitioning of elements between minerals during their formation and alteration. This research involves a collaboration of three institutions in different parts of the country, employs high temperature/atmospheric-pressure experiments to achieve research goals, and carries out a comparison of the geochemistry of seafloor igneous rocks from the Southwest Indian Ridge. Rock types include mid-ocean ridge basalts, also known as MORB, and abyssal peridotites which represent what is left over in Earth's upper mantle once MORB has been extracted by melting processes. Broader impacts of the work include interaction between scientists from universities and the Smithsonian Museum of Natural History, methods development that advances the infrastructure for science, and a strong integration of research and education. The project will involve the cross-training of a female PhD student who will travel between three laboratories and be trained in state-of-the-art geochemical analytical techniques, providing her with outstanding professional development and networking opportunities. Training of undergraduate students and a postdoc will also take place. The project supports three female researchers, one of whom is early career, and another who is from an institution in an EPSCoR (Experimental Program to Stimulate Competitive Research) state (Rhode Island). The researchers will use the Smithsonian public outreach engine to help implement and promote hands-on learning activities with seafloor rocks where the scientists interact directly with the public. The Smithsonian will also host and disseminate associated online mini-lessons.

This research involves petrologic, petrographic, and experimental work to examine the oxygen fugacity of the upper mantle and its variability. Rock samples come from an area of the seafloor that has an exceptional abundance of both basaltic and peridotitic material in close proximity. Most samples have already been well characterized analytically for major and trace elements and key radiogenic isotopes, allowing the research to focus on oxygen fugacity in a more efficient way. The research includes the cross-calibration of the two most frequently used oxybarometers in upper mantle studies: (1) oxygen fugacity determined from Fe3+/Total Fe ratios of mid-ocean ridge basalts determined by XANES, X-ray Absorption Near Edge Structure, spectroscopy and (2) oxygen fugacity derived from electron microprobe measurements of peridotite using Mossbauer-calibrated spinel standards. Because alteration can significantly impact oxybarometer signatures, its effects will be examined by comparing oxygen fugacity results of fresh and altered peridotites that have undergone various degrees of alteration. Experiments will be performed at 1 atm in a vertical gas mixing furnace at a range of oxygen fugacities that bracket the QFM (Quartz, Forsterite, Magnetite) buffer at a range of temperatures to 1225 C. Project goals include: (1) determining the oxygen fugacity of the upper mantle, (2) examining the processes that control the fugacity of oxygen in MORB and abyssal peridotite, and (3) trying to understand over what length scale oxygen fugacity in the mantle varies.

Earth's mantle is its largest layer by mass and volume and is ultimately the source of most of the magmas generated near Earth's surface. The chemistry and mineral composition of the rocks in Earth's mantle also serve as a time capsule that records events from the time of Earth's formation and its subsequent evolution caused by the recycling of near-surface materials back into the mantle through the processes of plate tectonics. This project is an experimental investigation of the chemistry of magmas that can be generated in Earth's mantle by different types of rocks that are likely to be found there. High pressure and high temperature experiments will be performed to investigate how the first-row transition elements (FRTE; Sc-Zn on the periodic table) and Ga and Ge behave during the formation of magmas in Earth's mantle. These elements are particularly useful for identify the types of rocks that may be melting to generate magmas. The results of this project will increase scientific knowledge of how magmas are formed on Earth and, through comparison with the chemistry of natural samples, will increase our understanding of the distribution of different rock types in Earth?s interior. Broader impacts of this research include support for an early-career researcher at a primarily undergraduate institution. The project will support training of a female graduate student who will gain expertise in formulating scientific questions, designing and performing experiments, analysis using several analytical methods, and interpretation and dissemination of experimental results. This project will also foster collaboration between the experimental lab at the University of Minnesota Duluth and the geochemistry and cosmochemistry lab at Florida State University, where analyses will be performed.

This research is an experimental study of the partitioning of FRTE between mantle minerals and melts, which will improve geochemical tools for identifying the source lithology of basaltic magmas. Experiments containing melts and either peridotite or pyroxenite mineral residues will be performed in a piston cylinder apparatus at conditions of mantle melt generation (pressures of 1.5 and 3 GPa and temperatures from 1270 to 1450 °C). These experiments will be doped with FRTE and Ga and Ge. The concentrations of these elements in the experimental run products (quenched melts and minerals) will be analyzed by laser ablation inductively-coupled plasma mass spectrometry (LA-ICP-MS). These analyses will yield partition coefficients for each element of interest between each mineral and coexisting melt. The project will aim to improve constraints on the concentrations and ratios of FRTE in melts generated by partial melting of peridotite and pyroxenite in Earth's mantle. Model melt compositions will be generated using these new experimental constraints and compared with the chemistry of natural basalts to better understand how lithological heterogeneity in the mantle is expressed in the chemistry of basaltic magmas. Better constraints on the source lithology of natural basalts will improve estimates of the abundance and distribution of recycled lithologies in Earth's upper mantle.