Mathematical model of fructan biosynthesis and polymer length distribution in plants

Background and Aims

There are many unresolved issues concerning the biochemistry of fructan biosynthesis. The aim of this paper is to address some of these by means of modelling mathematically the biochemical processes.

Methods

A model has been constructed for the step-by-step synthesis of fructan polymers. This is run until a steady state is achieved for which a polymer distribution is predicted. It is shown how qualitatively different distributions can be obtained.

Key Results

It is demonstrated how a set of experimental results on polymer distribution can by simulated by a simple parameter adjustments.

Conclusions

Mathematical modelling of fructan biosynthesis can provide a useful tool for helping elucidate the details of the biosynthetic processes.     

Proteins searching for their target on DNA by one-dimensional diffusion: overcoming the “speed-stability” paradox

The sequence dependence of DNA-protein interactions that allows proteins to find the correct reaction site also slows down the 1D diffusion of the protein along the DNA molecule, leading to the so-called “speed-stability paradox,” wherein fast diffusion along the DNA molecule is seemingly incompatible with stable targeting of the reaction site. Here, we develop diffusion-reaction models that use discrete and continuous Gaussian random 1D diffusion landscapes with or without a high-energy cut-off, and two-state models with a transition to and from a “searching” mode in which the protein diffuses rapidly without recognizing the target. We show the conditions under which such considerations lead to a predicted speed-up of the targeting process, and under which the presence of a “searching” mode in a two-state model is nearly equivalent to the existence of a high-energy cut-off in a one-state model. We also determine the conditions under which the search is either diffusion-limited or reaction-limited, and develop quantitative expressions for the rate of successful targeting as a function of the site-specific reaction rate, the roughness of the DNA-protein interaction potential, and the presence of a “searching” mode. In general, we find that a rough landscape is compatible with a fast search if the highest energy barriers can be avoided by “hopping” or by the protein transitioning to a lower-energy “searching” mode. We validate these predictions with the results of Brownian dynamics, kinetic Metropolis, and kinetic Monte Carlo simulations of the diffusion and targeting process, and apply these concepts to the case of T7 RNA polymerase searching for its target site on T7 DNA.     

Composite analysis of black duck breeding population surveys in eastern North America

Waterfowl are monitored in eastern Canada and the northeastern United States with 2 surveys: a transect survey from fixed-wing aircraft and a plot survey conducted from helicopters. The surveys vary in extent, but overlap exists in a core area of 9 strata covering portions of all provinces from Ontario east to Newfoundland. We estimated population change for American black ducks (Anas rubripes) and mallards (Anas platyrhynchos) from these surveys using a log-linear hierarchical model that accommodates differences in sample design and visibility associated with these survey methods. Using a combined analysis of the surveys based on total indicated birds, we estimate the American black duck population to be 901,700 (95% CI: 715,200–1,274,000) in 2011, with 526,900 (95% CI: 357,500–852,300) mallards in the surveyed area. Precision of estimates varies widely by species and region, with transect surveys providing less precise results than plot surveys for black ducks in areas of overlap. The combined survey analysis for black ducks in the eastern survey region produced estimates with an average yearly coefficient of variation (CV) of 12.1% for the entire area and an average CV of 6.9% in the plot survey area. Mallards, which had a more limited distribution in the region, had an average yearly CV of 22.1% over the entire region, and an average CV of 27.7% in the plot survey area. Hierarchical models provide a rich framework for analyzing and combining results from complex survey designs, providing useful spatial and temporal information on population size and change in these economically important species. © 2012 The Wildlife Society.     

Climate oscillations and species interactions: large‐scale congruence but regional differences in the phylogeographic structures of an alpine plant and its monophagous insect

Aim To predict the fate of alpine interactions involving specialized species, using a monophagous beetle and its host plant as a case study. Location The Alps. Methods We investigated genetic structuring of the herbivorous beetle Oreina gloriosa and its specific host‐plant Peucedanum ostruthium. We used genome fingerprinting (in the insect and the plant) and sequence data (in the insect) to compare the distribution of the main gene pools in the two associated species and to estimate divergence time in the insect, a proxy for the temporal origin of the interaction. We quantified the similarity in spatial genetic structures by performing a Procrustes analysis, a tool from shape theory. Finally, we simulated recolonization of an empty space analogous to the deglaciated Alps just after ice retreat by two lineages from two species showing unbalanced dependence, to examine how timing of the recolonization process, as well as dispersal capacities of associated species, could explain the observed pattern. Results Contrasting with expectations based on their asymmetrical dependence, patterns in the beetle and plant were congruent at a large scale. Exceptions occurred at a regional scale in areas of admixture, matching known suture zones in Alpine plants. Simulations using a lattice‐based model suggested these empirical patterns arose during or soon after recolonization, long after the estimated origin of the interaction c. 0.5 million years ago. Main conclusions Species‐specific interactions are scarce in alpine habitats because glacial cycles have limited the opportunities for co‐evolution. Their fate, however, remains uncertain under climate change. Here we show that whereas most dispersal routes are paralleled at a large scale, regional incongruence implies that the destinies of the species might differ under changing climate. This may be a consequence of the host dependence of the beetle, which locally limits the establishment of dispersing insects.     

Lipopolysaccharide-induced fever alters Hering–Breuer reflex in anesthetized rats

The aim of the study was to test the hypothesis that control of breathing via Hering–Breuer reflex (HB) is influenced by lipopolysaccharide (LPS)-induced fever in rats. Animals were injected intraperitoneally with LPS and control group with an equivalent volume of saline. HB reflex was elicited by inflations of the lungs followed by occlusion of the airways under control of esophageal pressure. Duration of HB reflex (T_apnoe) was continuously reduced as body temperature rose during experiment. Compared to normothermic controls, animals with fever had significant shortening of T_apnoe at 240 min and 300 min after LPS administration. Fever was further accompanied by a reduction in the strength of HB reflex (inhibitory ratio, IR). In comparison with controls, significant decrease of IR was observed at 300 min after LPS injection. Conclusion: altered neural control of breathing demonstrated by decreased power of Hering–Breuer inflation reflex in conditions of LPS-induced fever may facilitate thermal tachypnoea and/or play a role in the origin of respiratory instability accompanying febrile response.     

Analysing covariates with spike at zero: A modified FP procedure and conceptual issues

In epidemiology and in clinical research, risk factors often have special distributions. A common situation is that a proportion of individuals have exposure zero, and among those exposed, we have some continuous distribution. We call this a ‘spike at zero’. Examples for this are smoking, duration of breastfeeding, or alcohol consumption. Furthermore, the empirical distribution of laboratory values and other measurements may have a semi‐continuous distribution as a result of the lower detection limit of the measurement. To model the dose–response function, an extension of the fractional polynomial approach was recently proposed. In this paper, we suggest a modification of the previously suggested FP procedure. We first give the theoretical justification of this modified procedure by investigating relevant distribution classes. Here, we systematically derive the theoretical shapes of dose–response curves under given distributional assumptions (normal, log normal, gamma) in the framework of a logistic regression model. Further, we check the performance of the procedure in a simulation study and compare it to the previously suggested method, and finally we illustrate the procedures with data from a case–control study on breast cancer.     

Analysis of multivariate recurrent event data with time‐dependent covariates and informative censoring

Multivariate recurrent event data are usually encountered in many clinical and longitudinal studies in which each study subject may experience multiple recurrent events. For the analysis of such data, most existing approaches have been proposed under the assumption that the censoring times are noninformative, which may not be true especially when the observation of recurrent events is terminated by a failure event. In this article, we consider regression analysis of multivariate recurrent event data with both time‐dependent and time‐independent covariates where the censoring times and the recurrent event process are allowed to be correlated via a frailty. The proposed joint model is flexible where both the distributions of censoring and frailty variables are left unspecified. We propose a pairwise pseudolikelihood approach and an estimating equation‐based approach for estimating coefficients of time‐dependent and time‐independent covariates, respectively. The large sample properties of the proposed estimates are established, while the finite‐sample properties are demonstrated by simulation studies. The proposed methods are applied to the analysis of a set of bivariate recurrent event data from a study of platelet transfusion reactions.     

不稳定EGFP细胞模型的构建及其在基因编辑体系评价中的应用*

目的:为了更好地评价基因编辑效率,满足高通量筛选应用中快速、高效的检测要求,在细胞上建立一个原位检测方法具有重要的意义。通过检测荧光蛋白信号强度的变化可以评价CRISPR系统在细胞中的基因编辑情况,然而这一方法的效率受限于荧光蛋白较长的半衰期。方法:将鸟氨酸脱羧酶降解结构域(含PEST序列)与EGFP融合,通过慢病毒系统感染HEK-293T细胞,获得了表达单拷贝、EGFP-PEST报告基因的稳转细胞系。结果:与EGFP相比,EGFP-PEST在细胞内的降解速度明显加快,荧光水平在4 h内显著降低。利用该模型比较了3种商品化脂质体介导的CRISPR/Cas9基因编辑效率,能够在2~4 d实现定性和定量评价。结论:这一模型能够快速、灵敏地指示基因编辑效果,可以用于不同CRISPR系统或新递送工具的高通量筛选和评价。     

Cytokine and chemokine expression in a rat endometriosis is similar to that in human endometriosis

The pathogenesis of endometriosis, a gynecologic disorder associated with infertility, appears to involve immune responses. However, the details involved have not been clarified. In this study, we analyzed expression levels of interleukin (IL)-6, IL-10, monocyte chemoattractant protein-1, eosinophil chemotactic protein, macrophage inflammatory protein-1α, and regulated on activation normal T cell expressed and secreted (RANTES) and CC chemokine receptor 1 in endometriotic lesions in a rat model in which endometrium is autotransplanted onto peritoneal tissue and found that they were remarkably increased, while those of IL-2, IL-4, and interferon-γ were not. These results were obtained in a rat model induced by autologous, not allogeneic, transplantation of endometrial epithelium to the peritoneum. Expression of these factors is consistent with that of endometriosis in humans. Therefore, this model may be useful in the investigation of the pathogenesis and treatment of endometriosis.