A theory of optimal differential gene expression

We investigate a model of optimal regulation, intended to describe large-scale differential gene expression. Relations between the optimal expression patterns and the function of genes are deduced from an optimality principle: the regulators have to maximise a fitness function which they influence directly via a cost term, and indirectly via their control on important cell variables, such as metabolic fluxes. According to the model, the optimal linear response to small perturbations reflects the regulators' functions, namely their linear influences on the cell variables. The optimal behaviour can be realised by a linear feedback mechanism. Known or assumed properties of response coefficients lead to predictions about regulation patterns. A symmetry relation predicted for deletion experiments is verified with gene expression data. Where the optimality assumption is valid, our results justify the use of expression data for functional annotation and for pathway reconstruction and suggest the use of linear factor models for the analysis of gene expression data.     

The coded functions of noncoding RNAs for gene regulation

For eukaryotes, fine tuning of gene expression is necessary to coordinate complex genetic information. Recent studies have shown that noncoding RNAs (ncRNAs) play central roles in this process. For example, ncRNAs participate in multiple diverse functions such as mRNA degradation, epigenetic regulation and alternative splicing. The findings regarding this new player in gene regulation suggest that the mechanism of gene regulation is much more complicated and subtle than previously thought. In this review, new findings concerning the role of ncRNAs in gene regulation are discussed.     

RASSF tumor suppressor gene family: Biological functions and regulation

Genetic changes through allelic loss and nucleic acid or protein modifications are the main contributors to loss of function of tumor suppressor proteins. In particular, epigenetic silencing of genes by promoter hypermethylation is associated with increased tumor severity and poor survival. The RASSF (Ras association domain family) family of proteins consists of 10 members, many of which are tumor suppressor proteins that undergo loss of expression through promoter methylation in numerous types of cancers such as leukemia, melanoma, breast, prostate, neck, lung, brain, colorectal and kidney cancers. In addition to their tumor suppressor function, RASSF proteins act as scaffolding agents in microtubule stability, regulate mitotic cell division, modulate apoptosis, control cell migration and cell adhesion, and modulate NFκB activity and the duration of inflammation. The ubiquitous functions of these proteins highlight their importance in numerous physiological pathways. In this review, we will focus on the biological roles of the RASSF family members and their regulation.     

Constructing gene co-expression networks and predicting functions of unknown genes by random matrix theory

Background  

Large-scale sequencing of entire genomes has ushered in a new age in biology. One of the next grand challenges is to dissect the cellular networks consisting of many individual functional modules. Defining co-expression networks without ambiguity based on genome-wide microarray data is difficult and current methods are not robust and consistent with different data sets. This is particularly problematic for little understood organisms since not much existing biological knowledge can be exploited for determining the threshold to differentiate true correlation from random noise. Random matrix theory (RMT), which has been widely and successfully used in physics, is a powerful approach to distinguish system-specific, non-random properties embedded in complex systems from random noise. Here, we have hypothesized that the universal predictions of RMT are also applicable to biological systems and the correlation threshold can be determined by characterizing the correlation matrix of microarray profiles using random matrix theory.     

Function-valued adaptive dynamics and optimal control theory

In this article we further develop the theory of adaptive dynamics of function-valued traits. Previous work has concentrated on models for which invasion fitness can be written as an integral in which the integrand for each argument value is a function of the strategy value at that argument value only. For this type of models of direct effect, singular strategies can be found using the calculus of variations, with singular strategies needing to satisfy Euler’s equation with environmental feedback. In a broader, more mechanistically oriented class of models, the function-valued strategy affects a process described by differential equations, and fitness can be expressed as an integral in which the integrand for each argument value depends both on the strategy and on process variables at that argument value. In general, the calculus of variations cannot help analyzing this much broader class of models. Here we explain how to find singular strategies in this class of process-mediated models using optimal control theory. In particular, we show that singular strategies need to satisfy Pontryagin’s maximum principle with environmental feedback. We demonstrate the utility of this approach by studying the evolution of strategies determining seasonal flowering schedules.     

Metabolic regulation of neuron functions

A short analytical review of Soviet and foreign studies devoted to metabolic regulation of neuron functioning is presented. It is shown that the electrical activity of neuron is accompanied by structural changes and an increase in RNA content. It is assumed that these changes are initiated by calcium ions, coming to the neuron during its excitation. The principles of metabolic regulation of functioning of electro- and chemoexcitable neuronal membranes are considered. It is shown that the metabolic reactions can be an intermediate between the activated chemoreceptor and the electrical response of the cell. Evidence is presented that the electroexcitable and chemosensitive structures in the membrane modulate each other. The role of intracellular messengers in regulating the activity of receptors and channels is considered. Possible mechanisms for their modifications under the influence of cellular factors are discussed. It is shown that the work of neuron is controlled by several metabolic regulatory systems simultaneously.     

磷酸二酯酶的心血管功能调节作用

磷酸二酯酶(phosphodiesterase,PDE)是细胞内第二信使cAMP和cGMP降解的关键酶,作为药物研发的靶点受到广泛关注。近年研究发现,PDE在心肌细胞中能与β-肾上腺素受体及一些与兴奋收缩相关的蛋白形成复合物而使细胞内信号传递区室化分布,该现象可能为PDE抑制剂治疗慢性心力衰竭提供新的启示。血管平滑肌功能调节主要为血管张力和表型的调控,PDE5抑制剂舒张血管的作用已成功应用到勃起障碍的治疗。PDE4和PDE1C等在增殖的平滑肌细胞中表达量增高,单独抑制PDE的某一亚型将为治疗与平滑肌增殖有关的疾病(如肺动脉高压、血管成行术后再狭窄)提供新的途径。本文将重点阐述近年来PDE在心血管系统功能调节研究中的主要进展,以及PDE抑制剂在心血管系统疾病治疗中的应用。     

Epididymal functions and their hormonal regulation

The epididymis is a complex organ which maintains a specific intraluminal environment thought to be important for effecting sperm maturation in proximal regions and sperm storage in distal regions of the duct. The composition of the internal milieu is achieved both by transport between blood and lumen (and vice versa) and by synthesis and secretion into the lumen. Several low-molecular weight organic molecules achieve high concentration in the epididymal lumen, but their functions in the events of sperm maturation and storage still remain unclear. Metabolic processes occurring within epididymal tissue and the absorptive and secretory activity of the epididymal epithelium are regulated by androgens. The synthesis of some, but not all, secretory proteins is also androgen-dependent. In addition to androgens, other hormones and local testicular factors may influence epididymal function. There is now increasing evidence that epididymal-specific and androgen-dependent secretory proteins play a fundamental role in modifying the surface characteristics of sperm in preparation for the events of fertilization.     

Modular design of synthetic receptors for programmed gene regulation in cell therapies

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Redox regulation of cellular functions

Maintenance of normal intracellular redox status plays an important role in such processes as DNA synthesis, gene expression, enzymatic activity, and others. In addition, it is clear that changes in the redox status of intracellular content and individual molecules, resulting from stress or intrinsic cellular activity, are involved in the regulation of different processes in cells. Small changes in intracellular levels of reactive oxygen species participate in intracellular signaling. Thiol-containing molecules, such as glutathione, thioredoxins, glutaredoxins, and peroxiredoxins, also play an important role in maintaining redox homeostasis and redox regulation. This review attempts to summarize the current knowledge about redox regulation in different cell types.     

Integrating optimal foraging and optimal oviposition theory in plant–insect research

The current approach for studying host selection by phytophagous insects is mainly based on optimal oviposition theory, i.e. the preference–performance hypothesis. Almost no attention has been given to optimal foraging theory. However, recent papers and additional evidence given in this work illustrate that also optimal foraging may shape host preference patterns of phytophagous insects. Therefore and because optimal foraging and optimal oviposition may oppose conflicting needs to phytophagous insects, we plea for an integration of optimal foraging and optimal oviposition in plant–insect research. We argue how this may improve our understanding of plant–insect interactions.