Functional epistasis on a common MHC haplotype associated with multiple sclerosis

Genes in the major histocompatibility complex (MHC) encode proteins important in activating antigen-specific immune responses. Alleles at adjacent MHC loci are often in strong linkage disequilibrium; however, little is known about the mechanisms responsible for this linkage disequilibrium. Here we report that the human MHC HLA-DR2 haplotype, which predisposes to multiple sclerosis, shows more extensive linkage disequilibrium than other common caucasian HLA haplotypes in the DR region and thus seems likely to have been maintained through positive selection. Characterization of two multiple-sclerosis-associated HLA-DR alleles at separate loci by a functional assay in humanized mice indicates that the linkage disequilibrium between the two alleles may be due to a functional epistatic interaction, whereby one allele modifies the T-cell response activated by the second allele through activation-induced cell death. This functional epistasis is associated with a milder form of multiple-sclerosis-like disease. Such epistatic interaction might prove to be an important general mechanism for modifying exuberant immune responses that are deleterious to the host and could also help to explain the strong linkage disequilibrium in this and perhaps other HLA haplotypes.     

Herbaceous succession after burning of cut western juniper trees

The expansion of western juniper ( Juniperus occidentalis spp. occidentalis Hook.) in the northern Great Basin has resulted in the wide-scale conversion of sagebrush-steppe communities to juniper woodlands. Prescribed fire and mechanical cutting are the 2 main methods used to remove juniper and restore sagebrush steppe. Mechanical treatments commonly leave cut juniper on site. Disadvantages of leaving cut juniper are the increased fuel hazard and the potential for increased establishment and growth of invasive species. This study evaluated the response of herbaceous plants to winter burning of cut western juniper. Vegetation response was compared among 2 burning treatments (burning trees the first winter after cutting and burning the second winter after cutting), a control (cut-unburned juniper), and the interspace between cut trees. To minimize fire impacts to herbaceous perennials, cut trees were burned in the winter when soils and ground litter were frozen and/or soils were at field capacity. Only felled trees were burned, as fire did not carry into interspaces or litter mats around western juniper stumps. We hypothesized that winter season burning would increase herbaceous perennials and would reduce cheatgrass establishment when compared to the cut-unburned control. After 10 years, total herbaceous and perennial grass cover was 1.5- to 2-fold greater, respectively, in burned treatments compared to cut-unburned controls. Perennial grass density was 60% greater in the burned treatments than in the cut-unburned treatment and the interspace. Cheatgrass cover was twice as great in the control than in the 2 burn treatments and the interspace. We concluded that burning cut western juniper when soils were wet and frozen in winter enhanced community recovery of native perennials compared to leaving cut juniper unburned.     

Glutathione peroxidase, superoxide dismutase and catalase in the red blood cells of GSH-normal and GSH-deficient sheep

Levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase were measured in the red blood cells of glutathione(GSH)-normal and GSH-deficient sheep. There were no significant differences in any of the 3 enzyme activities measured in the 2 groups of sheep. Also, there was no relationship between GSH level and the enzyme activity. These results suggest that inspite of large differences in GSH levels, the red blood cells from GSH-normal and GSH-deficient Merino sheep appear to have similar response to oxidative stress against which GSH is credited to play a major role.     

Pharmacology: uncoupling the agony from ecstasy

The recreational use of amphetamine-type stimulants can produce a marked and sometimes lethal increase in body temperature. Here we show that mice deficient in a mitochondrial protein known as UCP-3 (for 'uncoupling protein-3') have a diminished thermogenic response to the drug MDMA (3,4-methylenedioxymethamphetamine, nicknamed 'ecstasy') and so are protected against this dangerously toxic effect. Our findings indicate that UCP-3 is important in MDMA-induced hyperthermia and point to a new therapeutic direction for solving an increasing public-health problem.     

Geophysics: a moving fluid pulse in a fault zone

In the Gulf of Mexico, fault zones are linked with a complex and dynamic system of plumbing in the Earth's subsurface. Here we use time-lapse seismic-reflection imaging to reveal a pulse of fluid ascending rapidly inside one of these fault zones. Such intermittent fault 'burping' is likely to be an important factor in the migration of subsurface hydrocarbons.