An abstract cell model that describes the self-organization of cell function in living systems

The principal aim of systems biology is to search for general principles that govern living systems. We develop an abstract dynamic model of a cell, rooted in Mesarovi? and Takahara's general systems theory. In this conceptual framework the function of the cell is delineated by the dynamic processes it can realize. We abstract basic cellular processes, i.e., metabolism, signalling, gene expression, into a mapping and consider cell functions, i.e., cell differentiation, proliferation, etc. as processes that determine the basic cellular processes that realize a particular cell function. We then postulate the existence of a 'coordination principle' that determines cell function. These ideas are condensed into a theorem: If basic cellular processes for the control and regulation of cell functions are present, then the coordination of cell functions is realized autonomously from within the system. Inspired by Robert Rosen's notion of closure to efficient causation, introduced as a necessary condition for a natural system to be an organism, we show that for a mathematical model of a self-organizing cell the associated category must be cartesian closed. Although the semantics of our cell model differ from Rosen's (M,R)-systems, the proof of our theorem supports (in parts) Rosen's argument that living cells have non-simulable properties. Whereas models that form cartesian closed categories can capture self-organization (which is a, if not the, fundamental property of living systems), conventional computer simulations of these models (such as virtual cells) cannot. Simulations can mimic living systems, but they are not like living systems.     

Modelling and analysis of gene regulatory networks

Gene regulatory networks have an important role in every process of life, including cell differentiation, metabolism, the cell cycle and signal transduction. By understanding the dynamics of these networks we can shed light on the mechanisms of diseases that occur when these cellular processes are dysregulated. Accurate prediction of the behaviour of regulatory networks will also speed up biotechnological projects, as such predictions are quicker and cheaper than lab experiments. Computational methods, both for supporting the development of network models and for the analysis of their functionality, have already proved to be a valuable research tool.     

Preparation of Highly Coupled Rat Heart Mitochondria

The function of mitochondria in generation of cellular ATP in the process of oxidative phosphorylation is widely recognised. During the past decades there have been significant advances in our understanding of the functions of mitochondria other than the generation of energy. These include their role in apoptosis, acting as signalling organelles, mammalian development and ageing as well as their contribution to the coordination between cell metabolism and cell proliferation. Our understanding of biological processes modulated by mitochondria is based on robust methods for isolation and handling of intact mitochondria from tissues of the laboratory animals. Mitochondria from rat heart is one of the most common preparations for past and current studies of cellular metabolism including studies on knock-out animals.Here we describe a detailed rapid method for isolation of intact mitochondria with a high degree of coupling. Such preparation of rat heart mitochondria is an excellent object for functional and structural research on cellular bioenergetics, transport of biomolecules, proteomic studies and analysis of mitochondrial DNA, proteins and lipids.     

The polyamines and their catabolic products are significant players in the turnover of nitrogenous molecules in plants

Polyamines (PAs) are nitrogenous molecules which play a well-established role in most cellular processes during growth and development under physiological or biotic/abiotic stress conditions. The molecular mode(s) of PA action have only recently started to be unveiled, and comprehensive models for their molecular interactions have been proposed. Their multiple roles are exerted, at least partially, through signalling by hydrogen peroxide (H(2)O(2)), which is generated by the oxidation/back-conversion of PAs by copper amine oxidases and PA oxidases. Accumulating evidence suggests that in plants the cellular titres of PAs are affected by other nitrogenous compounds. Here, we discuss the state of the art on the possible nitrogen flow in PAs, their interconnection with nitrogen metabolism, as well as the signalling roles of PA-derived H(2)O(2) during some developmental processes and stress responses.     

脂质组学研究进展

综述了脂质组学的研究现状和发展趋势.脂质组学是对生物体、组织或细胞中的脂质以及与其相互作用的分子进行系统分析的一门新兴学科.脂质具有多种重要的生物功能,脂质代谢异常可引发诸多人类疾病,包括糖尿病、肥胖症、癌症以及神经退行性疾病等.目前,脂质组学研究已成为一个前景广阔的热门领域,并广泛地应用到包括药物研发、分子生理学、分子病理学、功能基因组学、营养学以及环境与健康等重要领域.     

Vertex Models of Epithelial Morphogenesis

The dynamic behavior of epithelial cell sheets plays a central role during numerous developmental processes. Genetic and imaging studies of epithelial morphogenesis in a wide range of organisms have led to increasingly detailed mechanisms of cell sheet dynamics. Computational models offer a useful means by which to investigate and test these mechanisms, and have played a key role in the study of cell-cell interactions. A variety of modeling approaches can be used to simulate the balance of forces within an epithelial sheet. Vertex models are a class of such models that consider cells as individual objects, approximated by two-dimensional polygons representing cellular interfaces, in which each vertex moves in response to forces due to growth, interfacial tension, and pressure within each cell. Vertex models are used to study cellular processes within epithelia, including cell motility, adhesion, mitosis, and delamination. This review summarizes how vertex models have been used to provide insight into developmental processes and highlights current challenges in this area, including progressing these models from two to three dimensions and developing new tools for model validation.     

Vertex Models of Epithelial Morphogenesis

The dynamic behavior of epithelial cell sheets plays a central role during numerous developmental processes. Genetic and imaging studies of epithelial morphogenesis in a wide range of organisms have led to increasingly detailed mechanisms of cell sheet dynamics. Computational models offer a useful means by which to investigate and test these mechanisms, and have played a key role in the study of cell-cell interactions. A variety of modeling approaches can be used to simulate the balance of forces within an epithelial sheet. Vertex models are a class of such models that consider cells as individual objects, approximated by two-dimensional polygons representing cellular interfaces, in which each vertex moves in response to forces due to growth, interfacial tension, and pressure within each cell. Vertex models are used to study cellular processes within epithelia, including cell motility, adhesion, mitosis, and delamination. This review summarizes how vertex models have been used to provide insight into developmental processes and highlights current challenges in this area, including progressing these models from two to three dimensions and developing new tools for model validation.     

Mitochondria and the dynamic control of stem cell homeostasis

The maintenance of cellular identity requires continuous adaptation to environmental changes. This process is particularly critical for stem cells, which need to preserve their differentiation potential over time. Among the mechanisms responsible for regulating cellular homeostatic responses, mitochondria are emerging as key players. Given their dynamic and multifaceted role in energy metabolism, redox, and calcium balance, as well as cell death, mitochondria appear at the interface between environmental cues and the control of epigenetic identity. In this review, we describe how mitochondria have been implicated in the processes of acquisition and loss of stemness, with a specific focus on pluripotency. Dissecting the biological functions of mitochondria in stem cell homeostasis and differentiation will provide essential knowledge to understand the dynamics of cell fate modulation, and to establish improved stem cell‐based medical applications.     

Class III peroxidases and ascorbate metabolism in plants

Class III peroxidases (PODs) have many functions in plant metabolism mainly dependent on their various physiological reducing substrates. Their involvement in plant differentiation and in the response against environmental stress is well known. Several evidences underline that ascorbate (ASC) levels affect POD reactions and, as a consequence, interfere with the metabolic pathways controlled by these isoenzymes. Ascorbate peroxidases (APXs), enzymes belonging to a different class of peroxidases (class I), are often present in the same cellular compartments in which PODs are also active. Since both APXs and PODs specifically utilise hydrogen peroxide as oxidising substrate they can compete, when co-present, for the same substrate. In this review, attention focuses on some of the physiological processes in which both ASC metabolism and PODs are involved. In particular, the scavenging of reactive oxygen species (ROS) during photosynthesis, cell elongation and wall stiffening as well as programmed cell death have been considered thoroughly. The relations between PODs and ASC metabolism have been discussed also in the attempt to outline their relevance for the correct plant development as well as for the perception/response of external stimuli allowing plants to cope with unfavourable conditions.     

Sphingolipid players in the leukemia arena

Sphingolipids function as bioactive mediators of different cellular processes, mostly proliferation, survival, differentiation and apoptosis, besides being structural components of cellular membranes. Involvement of sphingolipid metabolism in cancerogenesis was demonstrated in solid tumors as well as in hematological malignancies. Herein, we describe the main biological and clinical aspects of leukemias and summarize data regarding sphingolipids as mediators of apoptosis triggered in response to anti-leukemic agents and synthetic analogs as inducers of cell death as well. We also report the contribution of molecules that modulate sphingolipid metabolism to development of encouraging strategies for leukemia treatment. Finally we address how deregulation of sphingolipid metabolism is associated to occurrence of therapy resistance both in vitro and in vivo. Sphingolipids can be considered promising therapeutic tools alone or in combination with other compounds, as well as valid targets in the attempt to eradicate leukemia and overcome drug resistance.     

Sphingolipid players in the leukemia arena

Sphingolipids function as bioactive mediators of different cellular processes, mostly proliferation, survival, differentiation and apoptosis, besides being structural components of cellular membranes. Involvement of sphingolipid metabolism in cancerogenesis was demonstrated in solid tumors as well as in hematological malignancies. Herein, we describe the main biological and clinical aspects of leukemias and summarize data regarding sphingolipids as mediators of apoptosis triggered in response to anti-leukemic agents and synthetic analogs as inducers of cell death as well. We also report the contribution of molecules that modulate sphingolipid metabolism to development of encouraging strategies for leukemia treatment. Finally we address how deregulation of sphingolipid metabolism is associated to occurrence of therapy resistance both in vitro and in vivo. Sphingolipids can be considered promising therapeutic tools alone or in combination with other compounds, as well as valid targets in the attempt to eradicate leukemia and overcome drug resistance.     

A scaffold-free in vitro model for osteogenesis of human mesenchymal stem cells

For studying cellular processes three-dimensional (3D) in vitro models are of a high importance. For tissue engineering approaches osseous differentiation is performed on 3D scaffolds, but material depending influences promote cellular processes like adhesion, proliferation and differentiation. To investigate developmental processes of mesenchymal stem cells without cell-substrate interactions, self-contained in vitro models mimicking physiological condition are required. However, with respect to scientific investigations and pharmaceutical tests, it is essential that these tissue models are well characterised and are of a high reproducibility. In order to establish an appropriate in vitro model for bone formation, different protocols are compared and optimised regarding their aggregate formation efficiency, homogeneity of the aggregates, the viability and their ability to induce differentiation into the osteogenic lineage. The protocols for the generation of 3D cell models are based on rotation culture, hanging drop technique, and the cultivation in non adhesive culture vessels (single vessels as well as 96 well plates). To conclude, the cultivation of hMSCs in 96 well non adhesive plates facilitates an easy way to cultivate homogenous cellular aggregates with high performance efficiency in parallel. The size can be controlled by the initial cell density per well and within this spheroids, bone formation has been induced.     

谷氨酰胺代谢与肿瘤

“谷氨酰胺代谢”是肿瘤细胞除Warburg效应外又一重要的能量代谢方式。迅速增殖的肿瘤细胞消耗谷氨酰胺（glutamine,Gin）来提供生长和增殖所需的能量和生物大分子原料,维持细胞内氧化还原稳态和参与细胞内信号通路的转导。肿瘤中原癌基因与抑癌基因的突变会影响Gin代谢。结合先进的诊断技术和研究手段将有利于了解肿瘤中Gln的生化代谢,揭示Gin代谢的关键环节,为依赖Gin的肿瘤提供治疗新策略。     

Solute and macromolecule diffusion in cellular aqueous compartments.

Diffusion of solutes and macromolecules in aqueous cellular compartments is required for numerous cellular processes including metabolism, second messenger signaling and protein-protein interactions. The view of the cell interior has evolved from that of a viscous gel to that of a watery but crowded compartment. Recent measurements of fluorescent probe diffusion using photobleaching, correlation microscopy and time-resolved anisotropy methods, have indicated unexpectedly high mobilities of small solutes and macromolecules. This review evaluates experimental evidence defining the rates and barriers for molecular diffusion in cells. Possible implications of regulated molecular diffusion as a rate-limiting step in cell metabolism, and with respect to the delivery of therapeutic agents, are discussed.