Positional syntenic cloning and functional characterization of the mammalian circadian mutation tau

The tau mutation is a semidominant autosomal allele that dramatically shortens period length of circadian rhythms in Syrian hamsters. We report the molecular identification of the tau locus using genetically directed representational difference analysis to define a region of conserved synteny in hamsters with both the mouse and human genomes. The tau locus is encoded by casein kinase I epsilon (CKIepsilon), a homolog of the Drosophila circadian gene double-time. In vitro expression and functional studies of wild-type and tau mutant CKIepsilon enzyme reveal that the mutant enzyme has a markedly reduced maximal velocity and autophosphorylation state. In addition, in vitro CKIepsilon can interact with mammalian PERIOD proteins, and the mutant enzyme is deficient in its ability to phosphorylate PERIOD. We conclude that tau is an allele of hamster CKIepsilon and propose a mechanism by which the mutation leads to the observed aberrant circadian phenotype in mutant animals.     

Immunotherapy: bewitched, bothered, and bewildered no more

The field of immunotherapy holds clear promise not only for the development of new approaches to cancer and other diseases, but also for providing fundamental insight into the human immune response. In order for this promise to be realized, however, the scientific community must overcome an array of challenges. These challenges reflect not only the difficulties inherent in conducting investigations in human patients, but also difficulties created by the culture and practice of our own institutions, reward structure, and funding mechanisms. We suggest steps to be taken to reinvigorate basic research in human subjects as part of the mainstream of science.     

Rooted in grass: Challenging patterns of knowledge exchange as a means of fostering social change in a southeast Minnesota farm community

By convening a multidisciplinary team(the Monitoring Team) that included farmers,university and agency researchers, andnon-profit staff; a small group of farmers insoutheast Minnesota, U.S.A., bolstered thelegitimacy of the sustainable agriculturemovement. Through the experience of forming ateam and working with individuals who operatedwithin the mainstream knowledge paradigm,farmers gained validation of their knowledgeabout farming, while researchers came to valuealternative knowledge systems. In the contextof a socially embedded movement, farmers wereempowered by sharing their knowledge withresearchers, and ultimately contributed to thesustainable agriculture movement by challengingtraditional patterns of knowledge exchange.     

Evidence for ozone formation in human atherosclerotic arteries

Here, we report evidence for the production of ozone in human disease. Signature products unique to cholesterol ozonolysis are present within atherosclerotic tissue at the time of carotid endarterectomy, suggesting that ozone production occurred during lesion development. Furthermore, advanced atherosclerotic plaques generate ozone when the leukocytes within the diseased arteries are activated in vitro. The steroids produced by cholesterol ozonolysis cause effects that are thought to be critical to the pathogenesis of atherosclerosis, including cytotoxicity, lipid-loading in macrophages, and deformation of the apolipoprotein B-100 secondary structure. We propose the trivial designation "atheronals" for this previously unrecognized class of steroids.     

Colicin-tolerant mutants of Escherichia coli: resistance of membranes to colicin E1

Colicin E1 blocks proline accumulation by membrane vesicles prepared from wild-type sensitive Escherichia coli. Two classes of mutant cells are unaffected by colicin. Vesicles from colicin-resistant strains are sensitive to colicin E1, whereas vesicles from colicin-tolerant strains are unaffected by colicin El. These results suggest that the colicin E1 receptor is on the cell membrane and that colicin-tolerant strains have altered membranes while colicin-resistant strains have altered cell walls.     

Use of U.S. croplands for biofuels increases greenhouse gases through emissions from land-use change

Most prior studies have found that substituting biofuels for gasoline will reduce greenhouse gases because biofuels sequester carbon through the growth of the feedstock. These analyses have failed to count the carbon emissions that occur as farmers worldwide respond to higher prices and convert forest and grassland to new cropland to replace the grain (or cropland) diverted to biofuels. By using a worldwide agricultural model to estimate emissions from land-use change, we found that corn-based ethanol, instead of producing a 20% savings, nearly doubles greenhouse emissions over 30 years and increases greenhouse gases for 167 years. Biofuels from switchgrass, if grown on U.S. corn lands, increase emissions by 50%. This result raises concerns about large biofuel mandates and highlights the value of using waste products.     

Constraints to the integration of the contagious caprine pleuropneumonia (CCPP) vaccine into Kenya's animal health delivery system

Animal health is key to successful livestock production in developing countries. The development and delivery of vaccines against major epidemic diseases is one component of improving animal health. This paper presents a case study from Kenya on the production and delivery of a vaccine against Contagious Caprine Pleuropneumonia (CCPP), a major disease of goats. The vaccine, while technically a viable preventative measure against CCPP, has not been well integrated into Kenya's animal health care system. From February through November, 1992, the authors explored the organizational and policy constraints to vaccine production and distribution. Data were obtained through interviews, field visits, and available documents. Results suggest an animal health system that 1) does not have a well developed infrastructure to track, identify, and control animal diseases; 2) tends to place greater emphasis on cattle, rather than small ruminant health care; and 3) is not well linked in terms of research, development, and extension services.