Richard H. White - US grants

Photoreceptor cells in animal eyes contain light-absorbing pigments derived from compounds called chromophores. These pigments are localized on densely packed layers of membrane within the photoreceptors. Assembly and ongoing turnover of the membranes and their photopigments may be crucial to features of vision such as light adaptation, but the role of turnover is not yet well understood. This project exploits special properties of the visual system of insects for attacking this problem. The hawkmoth Manduca develops from a larval caterpillar into an adult moth; if the larva has a diet deficient in chromophores (vitamin A-related compounds), the adult has severely impaired vision. Remarkably, simply "painting" the adult eyes with the compounds in a special solution has been found to partially restore visual sensitivity. This system now will be used to assess how the chromophore is synthesized into photopigment, how the chromophore and membranes interact, and how the photopigment is inserted into the membrane. Anatomical and biochemical methods will be used to examine the membrane ultrastructure, the localization of the photopigments, and the metabolism of chromophores. This preparation provides a novel approach to address a central issue in vision, and will yield useful information on nocturnal vision in an ecologically important group of insects.

This research project addresses a central issue in the cell biology of vision and photoreception: the mechanisms and significance of turnover of light- sensitive membrane and its constituent light-sensitive molecule (rhodopsin). The assembly of light-sensitive membranes in light receptors are being studied in the normal and also in the vitamin-A deprived condition. Intracellular membranes that serve as the precursors of photosensitive membranes accumulate as large masses within vitamin-A deficient photoreceptors. When such cells are exposed to very bright light that compensates for their relative insensitivity, the internal membrane is rapidly added to the light-sensitive membrane. This laboratory also is testing an hypothesis concerning the relationship between the biochemical pathway that is involved in the response to light and the regulation of assembly and degradation of the light-sensitive membrane in photoreceptors. Techniques being used include pharmacological agents that specifically mimic various steps in the biochemical pathway. The structural effects of these agents on photoreceptor cells will be studied with electron microscopy. Functional effects will be assessed with electrophysiological methods. The pathway by which vitamin A derivatives enter and are utilized by the retina to provide the light-sensitive molecules for photoreception is also being investigated.

Moore 9514769 There are marked anatomical differences in the central nervous systems of males and females. It appears that the gonadal hormone environment may play a substantial and integral role in the development of these differences. However, a component of structural differences also appears dependent on external stimuli received during development of the central nervous system. Dr. Moore is investigating the interrelationship of factors involved in developing differences in the central nervous system. The studies involve manipulation of the gonadal hormone mixture and the environmental experiences young animals encounter. The influence of these changes on anatomical characteristics of the nervous system are probed using sophisticated neuroanatomical techniques. These investigations will provide significant information about the factors important for the development of the nervous system. Additionally, information about the role of external environmental factors on the nervous system will also be defined. This information is crucial to understanding the ability of species to survive in the wild and reproduce successfully, and ultimately thrive in their natural habitats.

Objective: Our goal is to reduce the incidence of venous thromboembolism in the elderly. This project will be a comprehensive secondary analysis an existing data set to determine the incidence of thromboembolic complications in the first 3 months following a wide variety of different operations (n=approximately 60) and a wide spectrum of medical illnesses (n= approximately 30). Background: The majority of patients who develop deep-vein thrombosis (DVT) or pulmonary embolism (PE) are over the age of 60 years and recovering after major surgery or a major medical illness, particularly those with a malignancy. Most of the literature regarding the incidence of DVT after surgery actually refers to the incidence of asymptomatic venous thrombosis. We want to analyze the incidence of newly diagnosed DVT and PE within 3 months following a wide spectrum of different operations/illnesses to determine: 1) which operations or illnesses are associated with the highest rates of DVT and/or PE, 2) the effect of age as a risk factor for developing symptomatic DVT and PE, 3) the effect of race/ethnicity, and 4) the proportion of all thromboembolic complications that occur after hospital discharge. Methods: Using a large data set with linked records provided by the State of California (years 1993-1996), we will: 1) systematically select major illnesses and operations primarily affecting the elderly from the 25 major disease categories in the Diagnostic Related Groups, 2) select ICD-9-CM codes to precisely define the cohorts of interest, 3) determine the number and time of DVT and PE events, 4) create Kaplan-Meier plots of the 3 month cumulative incidence of thromboembolic events for each condition, 5) calculate the directly standardized (to California 1990 census) 3-month cumulative incidence of thromboembolic outcomes for each operation/condition, and 5) determine the effect of age by stratified analysis of the data (grouping ages = 55-64, 65-75, 76-up) as well as proportional hazards regression (or logistic regression) modeling, controlling for sex, race and malignancy. Implications. If it can be shown that: 1) certain previously unsuspected operations and medical illnesses are associated with high rates of clinical thromboembolic events, particularly among the elderly, and 2) if further case-control studies show a low prevalence of thromboprophylaxis among cases hospitalized for these operations/conditions, the findings will provide strong evidence that these patients should be treated more aggressively with thromboprophylaxis.

Insects that feed on flowers are particularly dependent on vision. Most visual research on insects has been done on species active during the day, or diurnal. We know little about the visual adaptations in nocturnal insects like moths that allow them to maneuver through a complex environment such as tropical forest, and find flowers in near darkness. Visually-guided behaviors such as nectar feeding from flowers are driven by specific color-sensitive sensory cells and specialized subdivisions of the retina of their large compound eyes. This project uses biochemistry and molecular biology to characterize and localize the light-sensitive proteins (rhodopsins) for color vision in the eye of the hawkmoth Manduca. Behavioral and anatomical work on other hawkmoth species which have day-feeding and non-feeding adults are compared to the night-feeding species. Results will highlight the particular adaptations for visual feeding at night, and be compared with the large knowledge base about flower visitation by bees and butterflies.
This project has ecological significance because a substantial proportion of tropical plant pollination depends on hawkmoths, and it also is important for evolutionary biology, as well as visual neurobiology.