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Journal Highlights

Cutting Sake's Head Off

Shimoi

Sake, a traditional alcoholic beverage from Japan, is brewed with sake yeasts (Saccharomyces cerevisiae). Almost all form a thick layer of foam on sake mash during fermentation, due to cell surface hydrophobicity and affinity for bubbles. Too much foam is undesirable, and for that reason, nonfoaming mutants have been bred. In an effort to better understand foaming, Hitoshi Shimoi and colleagues of the National Research Institute of Brewing, Japan, have cloned a gene that confers foaming ability on nonfoaming mutants. Dubbed AWA1, after awa, or foam in Japanese, the gene's protein is a GPI-anchored protein that localized to the cell wall. "An awa1 disruptant of sake yeast was hydrophilic and showed a nonfoaming phenotype," says Shimoi. "Generally, cell surface hydrophobicity is very important for survival and growth in natural environments. Now we are studying the structure of the AWA1 gene of nonfoaming mutants."

(H. Shimoi, K. Sakamoto, M. Okuda, R. Atthi, K. Iwashita, and K. Ito. 2002. The AWA1 gene is required for the foam-forming phenotype and cell surface hydrophobicity of sake yeast. Appl. Environ. Microbiol. 68:2018-2025.) 

Transgenic Mouse Models AIDS

(l to r) Hanna, Simard, Jolicoeur, Kay, and Chrobak

nef is an accessory gene present in the genomes of human immunodeficiency virus (HIV) types 1 and 2 and simian immunodeficiency virus. Paul Jolicoeur of the Clinical Research Institute of Montreal, Quebec, and others show that mice expressing the SIV_mac239 nef gene under the regulation of the CD4C promoter develop a disease very similar to human AIDS. "The presence of a severe thymic defect at birth in these mice is especially interesting because this resembles a problem experienced by a subgroup of HIV-1-infected children," says Jolicoeur. "This work also shows that SIV Nef harbors a major determinant of pathogenicity, independent of virus replication. The model represents a convenient tool to study the different pathologies present in AIDS. We are currently using this model to study the role of Nef on thymocyte differentiation and T-cell turnover as well as its effect on the bone marrow."

(M.-C. Simard, P. Chrobak, D.G. Kay, Z. Hanna, S. Jothy, and P. Jolicoeur. 2002. Expression of simian immunodeficiency virus nef in immune cells of transgenic mice leads to a severe AIDS-like disease. J. Virol. 76:3981-3995.) Abstract | Full Text

Lowering DNA Methylation Enzyme Levels Alters Cancer Risk in Genetically Predisposed Mice

Laird

The role of DNA methylation in cancer is not fully understood or appreciated. Methylation is a normal biological modification of DNA which helps regulate gene activity. Proper levels of DNA methylation are maintained by an enzyme called DNA methyltransferase 1 (Dnmt1). Peter W. Laird and colleagues of the University of Southern California show that reducing the levels of Dnmt1 in mice genetically predisposed to cancer suppresses tumor formation in the intestine, while enhancing it in the thymus. "This work illustrates both the potential benefit and the danger of using DNA methylation inhibitors in cancer prevention or treatment," says Laird. "We plan to investigate the molecular mechanisms responsible for these remarkable effects of DNA methylation on tumorigenesis in mice."

(B. N. Trinh, T. I. Long, A. E. Nickel, D. Shibata, and P. W. Laird. 2002. DNA methyltransferase deficiency modifies cancer susceptibility in mice lacking DNA mismatch repair. Mol. Cell. Biol. 22:2906-2917.) Abstract | Full Text

New Approach to Fighting Diphtheria

Diphtheria has recently reappeared as a potential threat to global health, in the former Soviet Union, Thailand, and elsewhere. The historical treatment, equine antitoxin, often caused serum sickness. Leon Eidels and colleagues of the University of Texas Southwestern Medical Center show that part of the diphtheria toxin receptor's extracellular domain can prevent the toxin's binding to cells. "This soluble receptor analog could neutralize circulating toxin in a diphtheria patient," says Eidels. "This approach could be useful for other toxin-mediated diseases, and in fact, the anthrax toxin receptor's extracellular domain has been shown to protect cells from the toxin. We now plan to test the soluble diphtheria toxin receptor analog to see if it will protect toxin-sensitive transgenic mice from the action of the toxin." (See Current Topics, p. 267.)

(J.-H. Cha, J. S. Brooke, M. Y. Chang, and L. Eidels. 2002. Receptor-based antidote for diphtheria. Infect. Immun. 70:2344-2350.) Abstract | Full Text

Researchers Change Phytase pH Optimum: Boon for Livestock Production

(l to r) Vogel, Lehman, Tomschy, Wyss, and Brugger

Phytases are used as feed supplements for pigs and poultry to increase dietary phosphorus availability, thus reducing fecal phosphorus excretion, and consequent eutrophication of surface waters. Most phytases function optimally at pHs of 5-7, but for best nutritional results, they should be optimally active at the pH of the animal's digestive tract. Andrea Tomschy and colleagues of Roche Vitamins, Ltd., Basel, Switzerland, and Novozymes A/S, of Denmark describe approaches to rationally engineer the pH activity profiles of phytases downward. "These findings significantly extend our tools for rationally designing an optimal phytase for a given purpose," says senior author Markus Wyss.

(A. Tomschy, R. Brugger, M. Lehmann, A. Svendsen, K. Vogel, D. Kostrewa, S. F. Lassen, D. Burger, A. Kronenberger, A. P. G. M. van Loon, L. Pasamontes, and M. Wyss. 2002. Engineering of phytase for improved activity at low pH. Appl. Environ. Microbiol. 68:1907-1913.) Abstract | Full Text

Intranasal Staph Enterotoxin A Protects against Enterotoxin-Mediated Toxic Shock

Collins

Toxic shock, a consequence of infection with Staphylococcus aureus, leads to multiple organ dysfunction and high mortality. L. Vincent Collins and colleagues at the University of Goteborg, Sweden, and Robert G. Ulrich, of the Army Medical Research Institute of Infectious Diseases, Frederick, Md., demonstrate that intranasal administration of the staphylococcal enterotoxin A (SEA) protects mice against enterotoxin-mediated shock. Protected mice survived a normally lethal systemic challenge with the toxin, while mice that had received an intranasal dose of nonsuperantigenic SEA were not protected against systemic challenge. "Interestingly, the resistance of these mice to toxic shock was due not to specific antibody responses, nor to removal of T cells that reacted with the superantigen, nor to silencing toxin-specific immune responses," says Collins. "Instead, the mice developed tolerance to the superantigen. The anti-inflammatory cytokine IL-10 appears to play a role in this process, probably by reducing systemic inflammatory responses."

(L. V. Collins, K. Eriksson, R. G. Ulrich, and A. Tarkowski. 2002. Mucosal tolerance of a bacterial superantigen indicates a novel pathway to prevent toxic shock. Infect. Immun. 70:2282-2287.) Abstract | Full Text