Biological weapons

Anthrax has been a major cause of death in grazing animals and an occasional cause of death in humans for thousands of years. Since the late 1800s there has been an exceptional international history of anthrax vaccine development. Due to animal vaccinations, the rate of infection has dropped dramatically. Anthrax vaccines have progressed from uncharacterized whole-cell vaccines in 1881, to pXO2-negative spores in the 1930s, to culture filtrates absorbed to aluminum hydroxide in 1970, and likely to recombinant protective antigen in the near future. Each of these refinements has increased safety without significant loss of efficacy. The threat of genetically engineered, antibiotic and vaccine resistant strains of Bacillus anthracis is fueling hypothesis-driven research and global techniques--including genomics, proteomics and transposon site hybridization--to facilitate the discovery of novel vaccine targets. This review highlights historical achievements and new developments in anthrax vaccine research.     

Heritable germline epimutation of MSH2 in a family with hereditary nonpolyposis colorectal cancer

Epimutations in the germline, such as methylation of the MLH1 gene, may contribute to hereditary cancer syndrome in human, but their transmission to offspring has never been documented. Here we report a family with inheritance, in three successive generations, of germline allele-specific and mosaic hypermethylation of the MSH2 gene, without evidence of DNA mismatch repair gene mutation. Three siblings carrying the germline methylation developed early-onset colorectal or endometrial cancers, all with microsatellite instability and MSH2 protein loss. Clonal bisulfite sequencing and pyrosequencing showed different methylation levels in different somatic tissues, with the highest level recorded in rectal mucosa and colon cancer tissue, and the lowest in blood leukocytes. This mosaic state of germline methylation with different tissue distribution could act as the first hit and provide a mechanism for genetic disease inheritance that may deviate from the mendelian pattern and be overlooked in conventional leukocyte-based genetic diagnosis strategy.     

Effect of ethanol on toxicity and metabolism of amphetamine in the mouse.

Ethanol, 3 g/kg i.p., did not significantly alter the acute toxicity of amphetamine in the mouse. However, the urinary metabolite pattern was changed, suggesting that ethanol suppressed metabolism of the stimulant during the initial 6 h period. After 24 h, the mouse metabolized the same fraction of a given dose of amphetamine, whether it was given as amphetamine alone or amphetamine mixed with 2,3 or 4 g/kg ethanol.     

Gene polymorphism in Netherton and common atopic disease.

Atopic dermatitis (AD) and asthma are characterized by IgE-mediated atopic (allergic) responses to common proteins (allergens), many of which are proteinases. Loci influencing atopy have been localized to a number of chromosomal regions, including the chromosome 5q31 cytokine cluster. Netherton disease is a rare recessive skin disorder in which atopy is a universal accompaniment. The gene underlying Netherton disease (SPINK5) encodes a 15-domain serine proteinase inhibitor (LEKTI) which is expressed in epithelial and mucosal surfaces and in the thymus. We have identified six coding polymorphisms in SPINK5 (Table 1) and found that a Glu420-->Lys variant shows significant association with atopy and AD in two independent panels of families. Our results implicate a previously unrecognized pathway for the development of common allergic illnesses.     

Roles of glial cells in synapse development

Brain function relies on communication among neurons via highly specialized contacts, the synapses, and synaptic dysfunction lies at the heart of age-, disease-, and injury-induced defects of the nervous system. For these reasons, the formation—and repair—of synaptic connections is a major focus of neuroscience research. In this review, I summarize recent evidence that synapse development is not a cell-autonomous process and that its distinct phases depend on assistance from the so-called glial cells. The results supporting this view concern synapses in the central nervous system as well as neuromuscular junctions and originate from experimental models ranging from cell cultures to living flies, worms, and mice. Peeking at the future, I will highlight recent technical advances that are likely to revolutionize our views on synapse–glia interactions in the developing, adult and diseased brain.     

Equilibrating metal-oxide cluster ensembles for oxidation reactions using oxygen in water.

Although many enzymes can readily and selectively use oxygen in water-the most familiar and attractive of all oxidants and solvents, respectively-the design of synthetic catalysts for selective water-based oxidation processes utilizing molecular oxygen remains a daunting task. Particularly problematic is the fact that oxidation of substrates by O2 involves radical chemistry, which is intrinsically non-selective and difficult to control. In addition, metallo-organic catalysts are inherently susceptible to degradation by oxygen-based radicals, while their transition-metal-ion active sites often react with water to give insoluble, and thus inactive, oxides or hydroxides. Furthermore, pH control is often required to avoid acid or base degradation of organic substrates or products. Unlike metallo-organic catalysts, polyoxometalate anions are oxidatively stable and are reversible oxidants for use with O2 (refs 8,9,10). Here we show how thermodynamically controlled self-assembly of an equilibrated ensemble of polyoxometalates, with the heteropolytungstate anion [AIVVW11O40]6- as its main component, imparts both stability in water and internal pH-management. Designed to operate at near-neutral pH, this system facilitates a two-step O2-based process for the selective delignification of wood (lignocellulose) fibres. By directly monitoring the central Al atom, we show that equilibration reactions typical of polyoxometalate anions keep the pH of the system near 7 during both process steps.     

On a dynamic mixture GARCH model

This paper proposes a new mixture GARCH model with a dynamic mixture proportion. The mixture Gaussian distribution of the error can vary from time to time. The Bayesian Information Criterion and the EM algorithm are used to estimate the number of parameters as well as the model parameters and their standard errors. The new model is applied to the S&P500 Index and Hang Seng Index and compared with GARCH models with Gaussian error and Student's t error. The result shows that the IGARCH effect in these index returns could be the result of the mixture of one stationary volatility component with another non‐stationary volatility component. The VaR based on the new model performs better than traditional GARCH‐based VaRs, especially in unstable stock markets. Copyright © 2008 John Wiley & Sons, Ltd.     

Riparian vegetation along the middle Snake River, Idaho: zonation, geographical trends, and historical changes

A baseline study was conducted on an 83-km free-flowing reach of the Snake River between Swan Falls Dam and the Idaho-Oregon border. The research had 2 components: (1) field characterization and inventory of existing riparian flora, vegetation, and environment (soils, topography, streamflow), and (2) determination and mapping, using a geographic information system, of historic changes in riparian vegetation based on a time series (1938-39, 1957, 1969, 1987) of aerial photographs. The flora was diverse, with 185 species of vascular plants identified, 63 of which were exotics. Vegetation was structured vertically along the riverbank gradient into lifeform-defined habitat types: emergent, riparian shrub-forb, tree, transitional grass-shrub, and upland. Riverbank seepage, probably of agricultural origin, blurred zonation patterns on some sites and added species to the overall flora. Upstream-downstream differences existed in the physical characteristics and vegetation of river subreaches. Coverage of riparian woodland, island riparian and total riparian vegetation, and area of islands increased since the 1930s, with the greatest changes in the 1969-1987 interval. Possible contributing facts were (1) significant declines in annual minimum flows since the 1950s, (2) decreases in peak flows following the completion of Swan Falls Dam and some upstream dams since the 1920s, (3) introduction and spread of exotic tree species ( Elaeagnus angustifolia and Tamarix spp.) and (4) possible effects of intensive agriculture on river sediment load and soil nutrients. The introduction and proliferation of purple loosestrife ( Lythrum salicaria ) could have considerable future effects on vegetation-channel dynamics in the middle Snake River.