Metastable behavior in Markov processes with internal states

A perturbation framework is developed to analyze metastable behavior in stochastic processes with random internal and external states. The process is assumed to be under weak noise conditions, and the case where the deterministic limit is bistable is considered. A general analytical approximation is derived for the stationary probability density and the mean switching time between metastable states, which includes the pre exponential factor. The results are illustrated with a model of gene expression that displays bistable switching. In this model, the external state represents the number of protein molecules produced by a hypothetical gene. Once produced, a protein is eventually degraded. The internal state represents the activated or unactivated state of the gene; in the activated state the gene produces protein more rapidly than the unactivated state. The gene is activated by a dimer of the protein it produces so that the activation rate depends on the current protein level. This is a well studied model, and several model reductions and diffusion approximation methods are available to analyze its behavior. However, it is unclear if these methods accurately approximate long-time metastable behavior (i.e., mean switching time between metastable states of the bistable system). Diffusion approximations are generally known to fail in this regard.     

Response of Picea rubens seedlings to intermittent mist varying in acidity, and in concentrations of sulfur-, and nitrogen-containing pollutants

Two-year-old red spruce seedlings ( Picea rubens Sarg .) growing in. field chambers were repeatedly exposed to acidic mist with a factorial combination of 3 fluctuating levels of acidity: median pH values of 3.0 (range of 2.5 to 3.5), 3.5 (range of 3.0 to 4.0), and 4.0 (range of 3.5 to 4.5). and 3 ion compositions: sulfate. nitrate and ammonium, and a combination of all 3 ions. The experiment was performed during the growing season over a period of 3.5 months. Mist exposures were intermittent with 5 wet-dry cycles for each 16-h overnight exposure period, Foliar necrosis occurred on seedlings treated with the most acidic mist and was most severe when the mist contained sulfate. At a median pH of 3.5, a value close to that of cloud water occurring in the eastern United States, injury developed with sulfuric acid mist, but not. when the mist contained nitric acid. The combination of high acidity and sulfate significantly decreased volume of aboveground tissues, while high acidity and nitrate increased volume. Root and needle dry weights were not affected. However, high acidity of mist was associated with increased leader shoot length. These results indicate, that there is a risk of foliar injury and changes in growth of red spruce with cloud water at a median acidity of pH 3.5 or below, especially when there are high concentrations of sulfate and low concentrations of nitrate.     

Direct anabolic metabolism of three-carbon propionate to a six-carbon metabolite occurs in vivo across tissues and species

Anabolic metabolism of carbon in mammals is mediated via the one- and two-carbon carriers S-adenosyl methionine and acetyl-coenzyme A. In contrast, anabolic metabolism of three-carbon units via propionate has not been shown to extensively occur. Mammals are primarily thought to oxidize the three-carbon short chain fatty acid propionate by shunting propionyl-CoA to succinyl-CoA for entry into the TCA cycle. Here, we found that this may not be absolute as, in mammals, one nonoxidative fate of propionyl-CoA is to condense to two three-carbon units into a six-carbon trans-2-methyl-2-pentenoyl-CoA (2M2PE-CoA). We confirmed this reaction pathway using purified protein extracts provided limited substrates and verified the product via LC-MS using a synthetic standard. In whole-body in vivo stable isotope tracing following infusion of ¹³C-labeled valine at steady state, 2M2PE-CoA was found to form via propionyl-CoA in multiple murine tissues, including heart, kidney, and to a lesser degree, in brown adipose tissue, liver, and tibialis anterior muscle. Using ex vivo isotope tracing, we found that 2M2PE-CoA also formed in human myocardial tissue incubated with propionate to a limited extent. While the complete enzymology of this pathway remains to be elucidated, these results confirm the in vivo existence of at least one anabolic three- to six-carbon reaction conserved in humans and mice that utilizes propionate.     

Host-Parasite Interactions and Purifying Selection in a Microsporidian Parasite of Honey Bees

To clarify the mechanisms of Nosema ceranae parasitism, we deep-sequenced both honey bee host and parasite mRNAs throughout a complete 6-day infection cycle. By time-series analysis, 1122 parasite genes were significantly differently expressed during the reproduction cycle, clustering into 4 expression patterns. We found reactive mitochondrial oxygen species modulator 1 of the host to be significantly down regulated during the entire infection period. Our data support the hypothesis that apoptosis of honey bee cells was suppressed during infection. We further analyzed genome-wide genetic diversity of this parasite by comparing samples collected from the same site in 2007 and 2013. The number of SNP positions per gene and the proportion of non-synonymous substitutions per gene were significantly reduced over this time period, suggesting purifying selection on the parasite genome and supporting the hypothesis that a subset of N. ceranae strains might be dominating infection.     

Computing the selection gradient and evolutionary response of an infinite-dimensional trait

 Following the results developed in a previous paper, an equation describing the evolutionary response to selection is extended from finite- to infinite-dimensional traits. The selection gradient and evolutionary response are then computed for a large class of infinite-dimensional traits of broad biological interest. In this framework, traits are modeled as Gaussian processes, and reproducing kernel Hilbert spaces constitute a primary tool. Received 12 September 1996