Gerald Goldstein - US grants

The objective of this investigation is to determine if the replication of Herpes simplex virus type 1(HSV-1) in vitro is inhibited by the substance known as 6-diazo-5-oxo-L-norleucine (DON) and specifically what the mechanism of inhibition is. Herpes simplex viruses cause orofacial and genital infections of humans and are the second most common cause of sexually transmitted disease. At the present time, acyclovir is only licensed prescription drug available for the treatment of HSV infections. Treatment of HSV infections with DON may prove to be an effective alternate therapy since some isolates are resistant to acyclovir. DON is an analogue of glutamine and as such inhibits the transfer of the amino group from glutamine to glucose, for the synthesis of glucosamine, and to nucleotide precursors for the synthesis of deoxyribonucleotides. Glucosamine is necessary for the synthesis of glycoproteins, and deoxyribonucleotides are necessary for the synthesis of DNA. Without glucosamine, enveloped viruses, like HSV, which are produced are not infectious and without deoxyribonucleotides, viral DNA synthesis is inhibited. Human epithelial (HEp-2) cells will be treated with DON prior to infection with HSV-1 to determine whether or not DON inhibits viral replication. If DON inhibits viral replication, experiments will be performed to determine if DON inactivates HSV-1 particles or interferes with viral adsorption to treated cells. DON is an analogue of glutamine and the addition of glutamine to medium containing DON prior to virus infection may reverse the inhibitory effects on viral replication. To determine if DON is affecting viral glycoprotein synthesis, viral DNA synthesis, or both, radioactively labeled glucosamine and thymidine will be added to DON treated, virus infected cells 4 hours post infection when host cell protein and DNA synthesis have been inhibited by the HSV-1 infection process. The addition of glucosamine and/or deoxyribonucleotides to DON treated HEp-2 cells prior to infection may specifically reverse the metabolic inhibition caused by DON and allow HSV-1 to replicate even in the presence of DON. Finally, HSV-1 particles produced in the presence of DON, if any, will be used to infect DON treated cells to determine if a population of viruses resistant to DON may arise. If successful, these experiments may lead to the clinical evaluation of the effectiveness of DON as a treatment for HSV infections.

Neuropsychological assessment is commonly used to aid in the diagnosis of dementia, or in the differential diagnosis of dementia and depression in the cognitively impaired elderly. Psychologists who administer these procedures are also called upon to make recommendations about the patients' level of functional capacity for the purpose of aftercare planning. However, without established predictive validity of these procedures psychologists rely upon clinical judgments in predicting functional outcome. The proposed research will determine whether neuropsychological assessment of a patient during hospitalization can predict specific functional skills assessed following discharge. One hundred and fifteen elderly inpatients of a specialized geriatric unit within an academically based psychiatric hospital will be entered into the study over a three year period. Subjects will be diagnosed as either probable Alzheimer's dementia, depression, or as having mixed features of dementia and depression. While in the inpatient unit, subjects will undergo a comprehensive research neuropsychological assessment battery assembled to predict to several activities of daily living (ADL) related areas including organizational aspects of self-care, instrumental behavior, communicative skills, practical memory, management of personal affairs, and ambulantion and transportation. At two weeks and again at six months following discharge from the hospital, patients will be visited in their residences and an extensive performance test of ADL functions involving direct behavioral observation of functional capacities will be administered by an Occupational Therapist. Statistical procedures will determine the extent to which the neuropsychological procedures accurately predict a number of functional ADL dimensions. In the event that these commonly employed diagnostic procedures can predict outcome, they may become highly useful prognostic instruments that may find a significant place in post-discharge planning with thecognitively impaired elderly.

The aim of this project is to significantly enhance the ability to teach about respiration and metabolism in a diversity of biology courses. The acquisition of a Micro-Oxymax computer- interfaced respirometer provides the sensitivity for measuring changes in CO2 as well as oxygen and allows animals to be monitored for extended periods of time without stress. By interfacing with the university computing systems the collected data is available to students in a variety of courses for additional analysis. The project has an impact on students in several courses, allowing them to take direct, accurate measurements of key metabolic processes, to investigate the influence of various environmental factors on their magnitude, and to develop "doable" experimental ideas of their own.

Ohio Wesleyan faculty and students will study the microbial ecosystem within avian plumage emphasizing those bacteria that degrade feather keratin. Molecular genetics will be used to study the control of the degradation process and biochemistry to study structural adaptations of the enzyme that cleaves the keratin molecule. Microbiologically will study how the diverse microorganisms within the plumage interact with feather-degrading bacteria. Lastly, the faculty and students will study how birds regulate this complex, microbial ecosystem that threatens their feathers and their survival. The interrelated biochemical, molecular, genetic, microbial, ecological, and evolutionary questions necessitate multidisciplinary approach.

Knowledge of the natural history of feather-degrading bacteria and their avian hosts, the genetic control of enzyme synthesis, and the biochemistry of degradation will enable the suggestion of environmentally safe methods of recovering small proteins and amino acids from waste feathers and efficient composting of dead poultry.

Seventy-two undergraduates, including 37 freshmen, have designed, completed, and reported their own research as partner in the current project. Each summer eight students will be offered research fellowships and one research associate position for a secondary science teacher. There will be an offer of four academic-year mentorships annually, which will build a commitment to research as student teaches student.