Molecular speciation and dynamics of oxidized triacylglycerols in lipid droplets: Mass spectrometry and coarse-grained simulations

Lipid droplets (LDs) are ubiquitous and physiologically active organelles regulating storage and mobilization of lipids in response to metabolic demands. Among the constituent LD neutral lipids, such as triacylglycerols, cholesterol esters, and free fatty acids, oxidizable polyunsaturated molecular species may be quite abundant, yet the structural and functional roles of their oxidation products have not been studied. Our previous work documented the presence of these peroxidized species in LDs. Assuming that hydrophilic oxygen-containing functionalities may markedly change the hydrophobic/hydrophilic molecular balance, here we utilized computational modeling to test the hypothesis that lipid peroxidation causes redistribution of lipids between the highly hydrophobic core and the polar surface (phospho)lipid monolayer—the area enriched with integrated enzymatic machinery. Using quantitative liquid chromatography/mass spectrometry, we characterized molecular speciation of oxTAGs in LDs of dendritic cells in cancer and hypoxic trophoblasts cells as two cellular models associated with dyslipidemia. Among the many types of oxidized lipids identified, we found that oxidatively truncated forms and hydroxyl derivatives of TAGs were the prevailing oxidized lipid species in LDs in both cell types. Using coarse-grained molecular dynamics (CG-MD) simulations we established that lipid oxidation changed their partitioning whereby oxidized lipids migrated into the outer monolayer of the LD, where they can affect essential metabolic pathways and undergo conversions, possibly leading to the formation of oxygenated lipid mediators.     

Neutral space analysis for a Boolean network model of the fission yeast cell cycle network

Background

Interactions between genes and their products give rise to complex circuits known as gene regulatory networks (GRN) that enable cells to process information and respond to external stimuli. Several important processes for life, depend of an accurate and context-specific regulation of gene expression, such as the cell cycle, which can be analyzed through its GRN, where deregulation can lead to cancer in animals or a directed regulation could be applied for biotechnological processes using yeast. An approach to study the robustness of GRN is through the neutral space. In this paper, we explore the neutral space of a Schizosaccharomyces pombe (fission yeast) cell cycle network through an evolution strategy to generate a neutral graph, composed of Boolean regulatory networks that share the same state sequences of the fission yeast cell cycle.

Results

Through simulations it was found that in the generated neutral graph, the functional networks that are not in the wildtype connected component have in general a Hamming distance more than 3 with the wildtype, and more than 10 between the other disconnected functional networks. Significant differences were found between the functional networks in the connected component of the wildtype network and the rest of the network, not only at a topological level, but also at the state space level, where significant differences in the distribution of the basin of attraction for the G₁ fixed point was found for deterministic updating schemes.

Conclusions

In general, functional networks in the wildtype network connected component, can mutate up to no more than 3 times, then they reach a point of no return where the networks leave the connected component of the wildtype. The proposed method to construct a neutral graph is general and can be used to explore the neutral space of other biologically interesting networks, and also formulate new biological hypotheses studying the functional networks in the wildtype network connected component.     

群落生态学的中性理论

生物多样性的分布格局和维持机制一直是群落生态学研究的核心问题,其中的关键是物种的共存机制。长期以来,生态位分化的思想在这一研究领域占据着主导地位。然而这一理论在解释热带雨林很高的物种多样性时遇到了困难。而以Hubbell为代表提出的群落中性漂变理论则假定在同一营养级物种构成的群落中不同物种的不同个体在生态学上可看成是完全等同的;物种的多度随机游走,群落中的物种数取决于物种灭绝和物种迁入/新物种形成之间的动态平衡。在这一假定之下,该理论预言了两种统计分布。一种是集合群落在点突变形成新物种的模式下其各个物种相对多度服从对数级数分布,而受扩散限制的局域群落以及按照随机分裂为新物种模式形成的集合群落则服从零和多项式分布。与生态位理论相反,中性理论不以种间生态位差异作为研究群落结构的出发点,而是以物种间在个体水平上的对等性作为前提。该理论第一次从基本生态学过程(出生、死亡、迁移、物种分化)出发,给出了群落物种多度分布的机理性解释,同时其预测的物种多度分布格局在实际群落中也得到了广泛的印证。因此,中性理论自诞生以来便在生态学界引发了极大的反响,也包括一些反对的声音。该文重点综述了关于中性理论的假设、预测和物种形成模式等方面的最新研究进展,包括中性理论本身的发展、关于中性理论的假设和预测的合理性检验以及在集合群落尺度上物种分化模式的讨论;并指出未来发展方向可能是在生态位理论和中性理论之间架起一座桥梁,同时发展包含随机性的群落生态位模型,以及允许种间差异的近中性模型。     

附子多糖FI的分离纯化及部分理化性质研究

白附片经热水抽提、Sevag法脱蛋白、乙醇沉淀、DEAE- C32柱层析分离 ,再通过 Sephadex G- 2 0 0柱层析进一步纯化 ,得到一种纯白色粉末状多糖 ,糖含量为 97% ,平均分子量为 2 .6× 10 5,熔点为 2 70℃。经完全酸水解、薄层层析、红外光谱分析 ,证明为葡聚糖。     

Assessing the suitability of genetic diversity of Chironomus riparius (Meigen) as an indicator of environmental pollution

Reliable and cost-effective indicators are needed to reduce uncertainty in ecological risk assessments of chemicals so that their long-term and evolutionary impacts in the dynamics of stressed biological communities can be accounted for.In the present study we investigate the suitability of genetic diversity as an indicator of ecological disturbance of freshwater ecosystems. For that, we selected three freshwater systems with well-known histories of metal contamination and three nearby reference sites located in Northern Portugal and the effects of metal contamination were assessed both in the levels of genetic diversity of the non-biting midge Chironomus riparius Meigen (at microsatellite markers) and in the diversity and composition of the benthic macroinvertebrate communities.Results showed a remarkable impoverishment in the abundance and diversity of macroinvertebrate communities of metal polluted sites in which most sensitive taxa were eliminated and replaced by more opportunistic ones belonging mainly to Oligochaeta and Diptera. In contrast, no evidence for pollution-induced genetic erosion was found in C. riparius populations in the studied area, with genetic diversity of the species being indeed higher in sites with impoverished macroinvertebrate communities and poor habitat quality.Our findings suggest that there are important limitations to the use of measures of genetic diversity of C. riparius per se to unravel ecological disturbance. Field studies aiming at quantifying pollutant-driven genetic erosion need to carefully consider the ecological and demographic aspects of potential target species.     

线性双滞量NDDE振动性的代数判据

本文给出一阶双滞量NDDE对所有参数振动与非振动的充要条件，这些条件用系统诸参数的若干代数式表达，方便于应用验证．     

Understanding how biodiversity unfolds through time under neutral theory

Theoretical predictions for biodiversity patterns are typically derived under the assumption that ecological systems have reached a dynamic equilibrium. Yet, there is increasing evidence that various aspects of ecological systems, including (but not limited to) species richness, are not at equilibrium. Here, we use simulations to analyse how biodiversity patterns unfold through time. In particular, we focus on the relative time required for various biodiversity patterns (macroecological or phylogenetic) to reach equilibrium. We simulate spatially explicit metacommunities according to the Neutral Theory of Biodiversity (NTB) under three modes of speciation, which differ in how evenly a parent species is split between its two daughter species. We find that species richness stabilizes first, followed by species area relationships (SAR) and finally species abundance distributions (SAD). The difference in timing of equilibrium between these different macroecological patterns is the largest when the split of individuals between sibling species at speciation is the most uneven. Phylogenetic patterns of biodiversity take even longer to stabilize (tens to hundreds of times longer than species richness) so that equilibrium predictions from neutral theory for these patterns are unlikely to be relevant. Our results suggest that it may be unwise to assume that biodiversity patterns are at equilibrium and provide a first step in studying how these patterns unfold through time.     

Molecular Weight of Human Brain Neutral Sphingomyelinase Determined In Situ by the Radiation Inactivation Method

The radiation inactivation method was used to determine the molecular weight of membrane-bound neutral sphingomyelinase from normal human brain. Inactivation curves showed a molecular mass of 167,000 +/- 32,000. Molecular weights of two control enzymes, beta-N-acetylglucosaminidase and nonspecific beta-glucosidase, determined by the same procedure, were consistent with previous reports.     

Compositional patterns in vertebrate genomes: Conservation and change in evolution

Summary The evolution of vertebrate genomes can be investigated by analyzing their regional compositional patterns, namely the compositional distributions of large DNA fragments (in the 30–100-kb size range), of coding sequences, and of their different codon positions. This approach has shown the existence of two evolutionary modes. In the conservative mode, compositional patterns are maintained over long times (many million years), in spite of the accumulation of enormous numbers of base substitutions. In the transitional, or shifting, mode, compositional patterns change into new ones over much shorter times.The conservation of compositional patterns, which has been investigated in mammalian genomes, appears to be due in part to some measure of compositional conservation in the base substitution process, and in part to negative selection acting at regional (isochore) levels in the genome and eliminating deviations from a narrow range of values, presumably corresponding to optimal functional properties. On the other hand, shifts of compositional patterns, such as those that occurred between cold-blooded and warm-blooded vertebrates, appear to be due essentially to both negative and positive selection again operating at the isochore level, largely under the influence of changes in environmental conditions, and possibly taking advantage of mutational biases in the replication/repair enzymes and/or in the enzyme make-up of nucleotide precursor pools. Other events (like translocations and changes in chromosomal structure) also play a role in the transitional mode of genome evolution.The present findings (1) indicate that isochores, which correspond to the DNA segments of individual or contiguous chromatin domains, represent selection units in the vertebrate genome; and (2) shed new light on the selectionist-neutralist controversy.This work was presented at the EMBO Workshop on Evolution (Cambridge, UK, 4–6 July 1988) and at the 16th International Congress of Genetics (Toronto, Canada, 20–27 August 1988)     

Influence of follower load application on moment-rotation parameters and intradiscal pressure in the cervical spine

The objective of this study was to implement a follower load (FL) device within a robotic (universal force-moment sensor) testing system and utilize the system to explore the effect of FL on multi-segment cervical spine moment-rotation parameters and intradiscal pressure (IDP) at C45 and C56. Twelve fresh-frozen human cervical specimens (C3-C7) were biomechanically tested in a robotic testing system to a pure moment target of 2.0 Nm for flexion and extension (FE) with no compression and with 100 N of FL. Application of FL was accomplished by loading the specimens with bilateral cables passing through cable guides inserted into the vertebral bodies and attached to load controlled linear actuators. FL significantly increased neutral zone (NZ) stiffness and NZ width but resulted in no change in the range of motion (ROM) or elastic zone stiffness. C45 and C56 IDP measured in the neutral position were significantly increased with application of FL. The change in IDP with increasing flexion rotation was not significantly affected by the application of FL, whereas the change in IDP with increasing extension rotation was significantly reduced by the application of FL. Application of FL did not appear to affect the specimen’s quantity of motion (ROM) but did affect the quality (the shape of the curve). Regarding IDP, the effects of adding FL compression approximates the effect of the patient going from supine to a seated position (FL compression increased the IDP in the neutral position). The change in IDP with increasing flexion rotation was not affected by the application of FL, but the change in IDP with increasing extension rotation was, however, significantly reduced by the application of FL.