Cycles and the Qualitative Evolution of Chemical Systems

Cycles are abundant in most kinds of networks, especially in biological ones. Here, we investigate their role in the evolution of a chemical reaction system from one self-sustaining composition of molecular species to another and their influence on the stability of these compositions. While it is accepted that, from a topological standpoint, they enhance network robustness, the consequence of cycles to the dynamics are not well understood. In a former study, we developed a necessary criterion for the existence of a fixed point, which is purely based on topological properties of the network. The structures of interest we identified were a generalization of closed autocatalytic sets, called chemical organizations. Here, we show that the existence of these chemical organizations and therefore steady states is linked to the existence of cycles. Importantly, we provide a criterion for a qualitative transition, namely a transition from one self-sustaining set of molecular species to another via the introduction of a cycle. Because results purely based on topology do not yield sufficient conditions for dynamic properties, e.g. stability, other tools must be employed, such as analysis via ordinary differential equations. Hence, we study a special case, namely a particular type of reflexive autocatalytic network. Applications for this can be found in nature, and we give a detailed account of the mitotic spindle assembly and spindle position checkpoints. From our analysis, we conclude that the positive feedback provided by these networks'' cycles ensures the existence of a stable positive fixed point. Additionally, we use a genome-scale network model of the Escherichia coli sugar metabolism to illustrate our findings. In summary, our results suggest that the qualitative evolution of chemical systems requires the addition and elimination of cycles.     

Introduced weed richness across altitudinal gradients in Hawai’i: humps,humans and water-energy dynamics

Native species richness commonly declines with increasing altitude, but patterns of introduced species richness across altitudinal gradients have been less frequently studied. We surveyed introduced roadside weeds along altitudinal transects ranging from 30 to 4,100 m in Hawai’i, with the objectives of (1) testing the hypothesis that a mass effect due to mixing of tropical and temperate species at mid-elevation promotes a hump-shaped pattern of introduced species richness with altitude, and (2) testing the potential roles of anthropogenic activity, energy (temperature) and water-energy dynamics (productivity-diversity hypothesis) in determining introduced weed richness. A total of 178 introduced weeds were recorded. Introduced weed richness does not decline monotonically with altitude. Rather, mixing of tropical and temperate species helps to maintain high mean richness up to 2,000 m, suggesting a mass effect, but without a distinct richness peak. Patchy occurrence of a transformer species, Pennisetum clandestinum, introduced high variance in richness at mid-elevations. General linear models considering estimated actual evapotranspiration (AET, a measure of energy-water dynamics) together with an index of human activity (distance from urban area or length of major roads) accounted for more variance in introduced weed richness than models with energy alone (temperature) and human activity. Native Hawaiian species richness along roadsides was also weakly correlated with AET but negatively associated with human activity. Our observed association between introduced species richness and AET mirrors patterns reported for native species richness around the world, indicating that AET-richness patterns can develop on a short time scale (on the order of 100 years). To test the generality of introduced weed richness patterns, we tried using the Hawai’i island model to predict weed richness on the neighboring island of Maui. Although weed richness on Maui was under-predicted, the same predictors (human activity and AET) were important on Maui. Scaling for differences in regional human population density or economic activity (both higher on Maui) may allow more accurate and transferable quantitative predictions of introduced weed richness patterns.     

Comparative analysis of plasma metabolomics response to metabolic challenge tests in healthy subjects and influence of the FTO obesity risk allele

The measurement of metabolites during intravenous or nutritional challenges may improve the identification of novel metabolic signatures which are not detectable in the fasting state. Here, we comprehensively characterized the plasma metabolomics response to five defined challenge tests and explored their use to identify interactions with the FTO rs9939609 obesity risk genotype. Fifty-six non-diabetic male participants of the KORA S4/F4 cohort, including 25 homozygous carriers of the FTO risk allele (AA genotype) and 31 carriers of the TT genotype were recruited. Challenges comprised an oral glucose tolerance test, a standardized high-fat high-carbohydrate meal and a lipid tolerance test, as well as an intravenous glucose tolerance test and a euglycemic hyperinsulinemic clamp. Blood was sampled for biochemical and metabolomics measurement before and during the challenges. Plasma samples were analyzed using a mass spectrometry-based metabolomics approach targeting 163 metabolites. Linear mixed-effects models and cluster analysis were performed. In both genotype groups, we observed significant challenge-induced changes for all major metabolite classes (amino acids, hexose, acylcarnitines, phosphatidylcholines, lysophosphatidylcholines and sphingomyelins, with corrected p-values ranging from 0.05 to 6.7E?37), which clustered in five distinct metabolic response profiles. Our data contribute to the understanding of plasma metabolomics response to diverse metabolic challenges, including previously unreported metabolite changes in response to intravenous challenges. The FTO genotype had only minor effects on the metabolite fluxes after standardized metabolic challenges.     

Metabolite profiling reveals new insights into the regulation of serum urate in humans

Metabolomics - Serum urate, the final breakdown product of purine metabolism, is causally involved in the pathogenesis of gout, and implicated in cardiovascular disease and type 2 diabetes. Serum...     

Migration cues induce chromatin alterations

Directed cell migration is a property central to multiple basic biological processes. Here, we show that directed cell migration is associated with global changes in the chromatin fiber. Polarized posttranslational changes in histone H1 along with a transient decrease in H1 mobility were detected in cells facing the scratch in a wound healing assay. In parallel to the changes in H1, the levels of the heterochromatin marker histone H3 lysine 9 tri-methylation were elevated. Interestingly, reduction of the chromatin-binding affinity of H1 altered the cell migration rates. Moreover, migration-associated changes in histone H1 were observed during nuclear motility in the simple multicellular organism Neurospora crassa . Our studies suggest that dynamic reorganization of the chromatin fiber is an early event in the cellular response to migration cues.