Branching stochastic processes with immigration in analysis of renewing cell populations

This paper considers the utility of a new class of stochastic branching processes with non-homogeneous immigration in modeling complex renewing cell systems. Such systems typically include the population of stem cells that provides an inexhaustible supply of cells necessary for maintaining the cellular composition of a tissue. A stem cell may be induced to transform (differentiate) into a progenitor cell. Progenitor cells retain the ability to proliferate and their function is believed to provide a quick proliferative response to an increased demand for cells in the population. There may be several sub-types of progenitor cells. Terminally differentiated cells do not divide under normal conditions; they are responsible for maintaining tissue-specific functions. Recent advancements in experimental techniques offer considerable scope for quantitative studies of in vivo cell kinetics based on stochastic modeling of renewing cell populations. However, no ready-made theory is currently available to take full advantage of these advancements. This paper introduces such a theory with a special focus on its feasibility in biological applications.     

The use of glycylhistidyllysine in culture systems

Summary Glycylhistidyllysine (GHL), a tripeptide isolated from plasma, has been shown to alter the growth rate of many cell types and organisms in culture systems. The tripeptide is optimally active at concentrations between 10 and 200 ng/ml. Some of the more interesting uses of GHL are highlighted in this paper. Present information suggests that GHL functions as a transporter of transition metals, in particular copper, to the cell surface for up-take into the cell. This work was supported by USPHS Grants CA 28858 and RR 05588.     

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.     

Evolutionary plasticity and functional versatility of CRISPR systems

The principal biological function of bacterial and archaeal CRISPR systems is RNA-guided adaptive immunity against viruses and other mobile genetic elements (MGEs). These systems show remarkable evolutionary plasticity and functional versatility at multiple levels, including both the defense mechanisms that lead to direct, specific elimination of the target DNA or RNA and those that cause programmed cell death (PCD) or induction of dormancy. This flexibility is also evident in the recruitment of CRISPR systems for nondefense functions. Defective CRISPR systems or individual CRISPR components have been recruited by transposons for RNA-guided transposition, by plasmids for interplasmid competition, and by viruses for antidefense and interviral conflicts. Additionally, multiple highly derived CRISPR variants of yet unknown functions have been discovered. A major route of innovation in CRISPR evolution is the repurposing of diverged repeat variants encoded outside CRISPR arrays for various structural and regulatory functions. The evolutionary plasticity and functional versatility of CRISPR systems are striking manifestations of the ubiquitous interplay between defense and “normal” cellular functions.

The CRISPR systems show remarkable functional versatility beyond their principal function as an adaptive immune mechanism. This Essay discusses how derived CRISPR systems have been recruited by transposons on multiple occasions and mediate RNA-guided transposition; derived CRISPR RNAs are frequently recruited for regulatory functions.     

Extracellular small RNAs: what, where, why?

miRNAs (microRNAs) are a class of small RNA that regulate gene expression by binding to mRNAs and modulating the precise amount of proteins that get expressed in a cell at a given time. This form of gene regulation plays an important role in developmental systems and is critical for the proper function of numerous biological pathways. Although miRNAs exert their functions inside the cell, these and other classes of RNA are found in body fluids in a cell-free form that is resistant to degradation by RNases. A broad range of cell types have also been shown to secrete miRNAs in association with components of the RISC (RNA-induced silencing complex) and/or encapsulation within vesicles, which can be taken up by other cells. In the present paper, we provide an overview of the properties of extracellular miRNAs in relation to their capacity as biomarkers, stability against degradation and mediators of cell-cell communication.     

Causes and Consequences of Eukaryotization Through Mutualistic Endosymbiosis and Compartmentalization

This paper reviews and extends ideas of eukaryotization by endosymbiosis. These ideas are put within an historical context of processes that may have led up to eukaryotization and those that seem to have resulted from this process. Our starting point for considering the emergence and development of life as an organized system of chemical reactions should in the first place be in accordance with thermodynamic principles and hence should, as far as possible, be derived from these principles. One trend to be observed is the ever-increasing complexity resulting in several layers of compartmentalization of the reaction system, either spatial (of which the eukaryotic cell is an example), or functional (as in the gradually deepening distinction between metabolic, enzymatic and information-storing functions within the cell). One of the causes of this complexification of living systems will have been the changes in environmental conditions, particularly the geochemical impoverishment of the biosphere during geological history, partly brought about by living systems themselves, and partly by the trend towards increasing efficiency and specificity of the reactions that occur.     

Cell-free protein synthesis for proteomics.

The use of cell-free expression systems as an alternative to cell-based methods for protein production is greatly facilitating studies of protein functions. Recent improvements to cell-free systems, and the development of cell-free protein display and microarray technologies, have led to cell-free protein synthesis becoming a powerful tool for large-scale analysis of proteins. This paper reviews the most commonly used cell-free systems and their applications in proteomics.     

Development of a neuronal pressure sensor

Neuronal sensory systems are capable of performing very complex signal processing functions. Reconstruction of such sensory systems in vitro should enable whole-cell biological sensors to be generated that possess inherent signal processing capabilities. In this paper, the results of preliminary investigations to produce a mechanosensory neuronal network are presented. An in vitro network of rat dorsal root ganglion neurons has been produced on a microelectrode plate revealing an interesting rhythmical pattern of spontaneous discharges. This periodic activity has been shown to be disrupted following the application of a static pressure to the cell culture. These results indicate that neuronal networks represent a practical system that may be used for the development of intelligent, whole-cell, biological sensors.     

The Application of Enterprise Modeling for Aerospace Manufacturing System Integration

The objective of enterprise modeling is to develop a repository regarding organizational elements and functions that maps information objectives with business functions. This is accomplished through an exhaustive process that analyzes and models the business to a level of detail sufficient to enable selection of appropriate technologies and the design of specific information systems. In this paper, enterprise modeling is utilized to provide a baseline reference for the successful integration of an FMS in an aerospace electronics manufacturing facility.     

根瘤菌群体感应系统研究进展*

群体感应是指细菌中依赖于细胞密度的基因表达调控过程,参与这种调节的系统被称为群体感应系统。N-酰基高丝氨酸内酯是大多数革兰氏阴性细菌群体感应系统的信号分子。这种系统调节细菌各种生理学反应和某些特定功能。在根瘤菌与宿主豆科植物成功建立共生关系的过程中,起着重要作用。详细的综述了根瘤菌中已发现的群体感应系统,并阐述了这种系统的调节功能和对实际应用的指导意义。     

Evolving cell models for systems and synthetic biology

This paper proposes a new methodology for the automated design of cell models for systems and synthetic biology. Our modelling framework is based on P systems, a discrete, stochastic and modular formal modelling language. The automated design of biological models comprising the optimization of the model structure and its stochastic kinetic constants is performed using an evolutionary algorithm. The evolutionary algorithm evolves model structures by combining different modules taken from a predefined module library and then it fine-tunes the associated stochastic kinetic constants. We investigate four alternative objective functions for the fitness calculation within the evolutionary algorithm: (1) equally weighted sum method, (2) normalization method, (3) randomly weighted sum method, and (4) equally weighted product method. The effectiveness of the methodology is tested on four case studies of increasing complexity including negative and positive autoregulation as well as two gene networks implementing a pulse generator and a bandwidth detector. We provide a systematic analysis of the evolutionary algorithm’s results as well as of the resulting evolved cell models.     

Cell division: control of the chromosomal passenger complex in time and space

The ultimate goal of cell division is equal transmission of the duplicated genome to two new daughter cells. Multiple surveillance systems exist that monitor proper execution of the cell division program and as such ensure stability of our genome. One widely studied protein complex essential for proper chromosome segregation and execution of cytoplasmic division (cytokinesis) is the chromosomal passenger complex (CPC). This highly conserved complex consists of Borealin, Survivin, INCENP, and Aurora B kinase, and has a dynamic localization pattern during mitosis and cytokinesis. Not surprisingly, it also performs various functions during these phases of the cell cycle. In this review, we will give an overview of the latest insights into the regulation of CPC localization and discuss if and how specific localization impacts its diverse functions in the dividing cell.     

P38MAPK信号传导通路与卵巢癌关系的研究进展

丝裂原活化蛋白激酶（mitogen-activatedproteinkinases,MAPKs）级联反应是细胞内重要的信号传导系统之一,参与细胞生长、发育、分化和凋亡等一系列生理、病理过程．P38MAPK信号传导通路是MAPK通路的分支之一,介导了应激、炎性细胞因子、细菌产物等多种刺激引起的细胞反应,对细胞周期调控具有重要作用．但对不同的卵巢癌细胞系,或者不同的刺激,P38通路的作用不完全相同,甚至可能相反,提示对P38通路的功能仍需进一步的研究,他可能是肿瘤治疗的新靶点．本文就P38MAPK信号传导通路与卵巢癌关系作一综述。     

Initial/boundary-value problems of tumor growth within a host tissue

This paper concerns multiphase models of tumor growth in interaction with a surrounding tissue, taking into account also the interplay with diffusible nutrients feeding the cells. Models specialize in nonlinear systems of possibly degenerate parabolic equations, which include phenomenological terms related to specific cell functions. The paper discusses general modeling guidelines for such terms, as well as for initial and boundary conditions, aiming at both biological consistency and mathematical robustness of the resulting problems. Particularly, it addresses some qualitative properties such as a priori non-negativity, boundedness, and uniqueness of the solutions. Existence of the solutions is studied in the one-dimensional time-independent case.     

P38 MAPK 信号传导通路与卵巢癌关系的研究进展

丝裂原活化蛋白激酶(mitogen-activated proteinkinases,MAPKs)级联反应是细胞内重要的信号传导系统之一,参与细胞生长、发育、分化和凋亡等一系列生理、病理过程.P38 MAPK信号传导通路是MAPK通路的分支之一,介导了应激、炎性细胞因子、细菌产物等多种刺激引起的细胞反应,对细胞周期调控具有重要作用.但对不同的卵巢癌细胞系,或者不同的刺激,P38通路的作用不完全相同,甚至可能相反,提示对P38通路的功能仍需进一步的研究,他可能是肿瘤治疗的新靶点.本文就P38 MAPK信号传导通路与卵巢癌关系作一综述。     

细胞膜仿生修饰纳米粒肿瘤治疗的研究进展

大量研究证明,细胞膜仿生修饰通过将不同细胞膜包被于纳米粒表面,赋予纳米粒新的生物学功能.纳米粒被细胞膜仿生修饰后,获得了细胞膜表面丰富的蛋白质并保留了纳米粒的高载药能力,延长体内循环时间,使纳米粒具有逃避免疫系统,跨越各种生理屏障的能力.本文总结了近年来细胞膜仿生修饰纳米粒用于肿瘤治疗的最新进展,讨论了细胞膜仿生修饰纳...     

Modulation of host signaling and cellular responses by <Emphasis Type="Italic">Chlamydia</Emphasis>

Modulation of host cell signaling and cellular functions is key to intracellular survival of pathogenic bacteria. Intracellular growth has several advantages e.g. escape from the humoral immune response and access to a stable nutrient rich environment. Growth in such a preferred niche comes at the price of an ongoing competition between the bacteria and the host as well as other microbes that compete for the very same host resources. This requires specialization and constant evolution of dedicated systems for adhesion, invasion and accommodation. Interestingly, obligate intracellular bacteria of the order Chlamydiales have evolved an impressive degree of control over several important host cell functions. In this review we summarize how Chlamydia controls its host cell with a special focus on signal transduction and cellular modulation.     

Versatility of peroxisomes: An evolving concept

Research spanning almost 50 years has highlighted unique characteristics and irreplaceable list of diverse functions performed by peroxisomes in various model systems. Peroxisomes are single membrane bound highly dynamic organelles ubiquitous to most eukaryotic cells. Proliferation by division of pre-existing organelles and the role of endoplasmic reticulum in the biogenesis of these organelles is now well established. The earliest identified conserved functions of peroxisomes are β-oxidation of fatty acids and reactive oxygen species metabolism. Several studies over the last few decades have reported the importance of this organelle and its numerous cell type, tissue and environment-dependent functions. Their role in several aspects of human health and disease is now under investigation. Studies related to peroxisome biology and functions are now also extended to diverse model systems like Drosophila melanogaster, trypanosomatids, etc. Peroxisomes also intricately collaborate and carry out these functions together with several other organelles in a cell. In this review, we aim to present an overview of our current knowledge of the repertoire of functions of peroxisomes in various model systems.