Classification of Cell Signalling in Tissue Development

Abstract

The traditional classification of signalling in biological systems is insufficient and outdated and novel efforts must take into account advances in systems theory, information theory and linguistics. We present some of the classification systems currently used both within and outside of the biological field and discuss some specific aspects of the nature of signalling in tissue development. The analytical methods used in understanding non-biological networks provide a valuable vocabulary, which requires integration and a system of classification to further facilitate development.     

Error-prone signalling.

The handicap principle of Zahavi is potentially of great importance to the study of biological communication. Existing models of the handicap principle, however, make the unrealistic assumption that communication is error free. It seems possible, therefore, that Zahavi's arguments do not apply to real signalling systems, in which some degree of error is inevitable. Here, we present a general evolutionarily stable strategy (ESS) model of the handicap principle which incorporates perceptual error. We show that, for a wide range of error functions, error-prone signalling systems must be honest at equilibrium. Perceptual error is thus unlikely to threaten the validity of the handicap principle. Our model represents a step towards greater realism, and also opens up new possibilities for biological signalling theory. Concurrent displays, direct perception of quality, and the evolution of 'amplifiers' and 'attenuators' are all probable features of real signalling systems, yet handicap models based on the assumption of error-free communication cannot accommodate these possibilities.     

ARE WARNING COLORS HANDICAPS?

The handicap theory, in which the cost of waste guarantees honest advertising, is being used increasingly in solutions to the problems of biological signal evolution. However, it is usually applied to systems which are insufficiently understood to allow testing against alternative theories. In particular, the ability of the handicap theory to explain the design of signals has never been properly tested. We test its ability to explain signal design features in an unusually well studied area of biological signalling: warning coloration and mimicry. Since a full handicap model proves immediately unrealistic, we modify the model to incorporate realistic assumptions about predator learning. Using this model we explicitly compare the handicap theory with a purely “conventional” signalling model and with a null model. Predictions relating to three key design features (conspicuousness, pattern similarity, and Batesian mimicry) are compared, and tested against available data. Although many predictions remain to be tested adequately, we conclude that: (i) conspicuousness is most plausibly explained by the conventional signalling theory that ascribes the function of conspicuous coloration to signal efficacy rather than waste; (ii) pattern similarity, within and between species, is unlikely to be the result of the need to produce similar degrees of conspicuousness, as predicted by the handicap theory, but is plausibly explained as the result of pattern generalization amongst discriminating predators, as predicted by the conventional signalling theory; and (iii) Batesian mimicry is predicted by the conventional signalling theory, but not the handicap theory. Therefore the handicap theory fails to provide an adequate explanation of the main design features of at least one major signalling system.     

Getting the most out of Shannon information

Shannon information is commonly assumed to be the wrong way in which to conceive of information in most biological contexts. Since the theory deals only in correlations between systems, the argument goes, it can apply to any and all causal interactions that affect a biological outcome. Since informational language is generally confined to only certain kinds of biological process, such as gene expression and hormone signalling, Shannon information is thought to be unable to account for this restriction. It is often concluded that a richer, teleosemantic sense of information is needed. I argue against this view, and show that a coherent and sufficiently restrictive theory of biological information can be constructed with Shannon information at its core. This can be done by paying due attention some crucial distinctions: between information quantity and its fitness value, and between carrying information and having the function of doing so. From this I construct an account of how informational functions arise, and show that the “subject matter” of these functions can easily be seen as the natural information dealt with by Shannon’s theory.     

The manipulation of calcium oscillations by harnessing self-organisation

This paper investigates how self-organisation might be harnessed for the manipulation and control of calcium oscillations. Calcium signalling mechanisms are responsible for a number of important functions within biological systems, such as fertilization, secretion, contraction, neuronal signalling and learning. In this paper, calcium oscillations are investigated as a biological periodic process. Within biological systems such periodic behaviour is one of the outcomes from self-organisation. The understanding of periodic processes in living systems can enable more accurate diagnosis and physiologically suitable clinical therapies to be proposed, for diseases such as cancer, epilepsy, cardiac diseases and other dynamic diseases. In this paper these ideas are investigated by means of the calcium-induced calcium release (CICR) model and a number of representative simulations of intra and inter-cellular calcium oscillations are used to illustrate the manipulation and control of these oscillations in normal and pathological situations.     

Systems biomedicine: It’s your turn —Recent progress in systems biomedicine

The concept of “systems biology” is raised by Hood in 1999. It means studying all components with a systematic view. Systems biomedicine is the application of systems biology in medicine. It studies all components in a whole system and aims to reveal the patho-physiologic mechanisms of disease. In recent years, with the development of both theory and technology, systems biomedicine has become feasible and popular. In this review, we will talk about applications of some methods of omics in systems biomedicine, including genomics, metabolomics (proteomics, lipidomics, glycomics), and epigenomics. We will particularly talk about microbiomics and omics for common diseases, two fields which are developed rapidly recently. We also give some bioinformatics related methods and databases which are used in the field of systems biomedicine. At last, some examples that illustrate the whole biological system will be given, and development for systems biomedicine in China and the prospect for systems biomedicine will be talked about.“     

G-proteins as transducers in transmembrane signalling

The G-protein-mediated signalling system has evolved as one of the most widely used transmembrane signalling mechanisms in mammalian organisms. All mammalian cells express G-protein-coupled receptors as well as several types of heterotrimeric G-proteins and effectors. G-protein-mediated signalling is involved in many physiological and pathological processes. This review summarizes some general aspects of G-protein-mediated signalling and focusses on recent data especially from studies in mutant mice which have elucidated some of the cellular and biological functions of heterotrimeric G-prtoteins.     

Pattern formation by local self-activation and lateral inhibition

In 1972, we proposed a theory of biological pattern formation in which concentration maxima of pattern forming substances are generated through local self-enhancement in conjunction with long range inhibition. Since then, much evidence in various developmental systems has confirmed the importance of autocatalytic feedback loops combined with inhibitory interaction. Examples are found in the formation of embryonal organizing regions, in segmentation, in the polarization of individual cells, and in gene activation. By computer simulations, we have shown that the theory accounts for much of the regulatory phenomena observed, including signalling to regenerate removed parts. These self-regulatory features contribute to making development robust and error-tolerant. Furthermore, the resulting pattern is, to a large extent, independent of the details provided by initial conditions and inducing signals.     

Combretastatin analogues in cancer biology: A prospective view

The stilbenoid combretastatin and its derivatives are potent inhibitors of angiogenesis and cell proliferation and induce apoptosis. They disrupt cytoskeletal dynamics and modulate cell morphology, motility, and invasion. Hence they have been viewed as potential as anticancer agents. The impediments of poor solubility and bioavailability and the spontaneous geometric isomerisation of combretastatin into an inactive form have led to intensive efforts towards evolving novel analogues to provide more efficacious biological outcome. Importantly, isomerically stable and biologically active cis-restricted analogues have been synthesised and tested. However, very few analogues have been tested in preclinical models to assess their effects on processes relevant to cancer development and progression. Hence the accent here is on the signalling systems operated by the new derivatives and their biological effects with reference to cancer progression. Combretastatins modulate an extensive network of signalling emphasising their varied versatility. Harnessing these systems and accentuating or counteracting aberrant signalling could open potential avenues of approach to the designing of novel derivatives with enhanced performance. The import of mammalian target of rapamycin pathway, which co-ordinates growth factor receptor signalling, epithelial-mesenchymal transition activation and angiogenic signalling, is emphasised. It may be viewed as a prime target for allosteric inhibition in combination with combretastatin analogues to ascertain their potential in cancer control.     

A highly sensitive near‐infrared fluorescent detection method to analyze signalling pathways by reverse‐phase protein array

The comprehensive and quantitative analysis of the protein phosphorylation patterns in different cellular context is of considerable and general interest. The ability to quantify phosphorylation of discrete signalling proteins in large collections of biological samples would greatly favour the development of systems biology in the field of cell signalling. Reverse‐phase protein array (RPPA) potentially represents a very attractive approach to map signal transduction networks with high throughput. In the present report, we describe an improved detection method for RPPA combining near‐infrared with one or two rounds of tyramide‐based signal amplification. The LOQ was lowered from 6.84 attomoles with a direct detection protocol to 0.21 attomole with two amplification steps. We validated this method in the context of intracellular signal transduction triggered by follicle‐stimulating hormone in HEK293 cells. We consistently detected phosphorylated proteins in the sub‐attomole range from less than 1 ng of total cell extracts. Importantly, the method correlated with Western blot analysis of the same samples while displaying excellent intra‐ and inter‐slide reproducibility. We conclude that RPPA combined with amplified near‐infrared detection can be used to capture the subtle regulations intrinsic to signalling network dynamics at an unprecedented throughput, from minute amounts of biological samples.     

Artificial Immune Systems-Based Classification Model for Code-Mixed Social Media Data

The main focus of the paper is to propose an artificial immune systems-based classification model for code-mixed social media data. The artificial immune systems are computational models inspired by the biological immune system. In this paper, artificial immune systems are used to optimize the initial parameters of Long short-term memory (LSTM) model. The proposed artificial immune systems-based LSTM model is then used for the classification of code-mixed data. The classification of Hindi-English code-mixed data into Hindi, English, and ambiguous words is done. Popular word embedding features were used for the representation of each word. The word embedding features and character embedding features have been used. The proposed method helps in identifying the word context by extracting the intent of user for using the ambiguous word in code-mixed sentence. Extensive experiments reveal that the artificial immune systems-based classification model outperforms competitive models especially when there are some ambiguous words in the social media data.     

An evolutionary system using development and artificial Genetic Regulatory Networks for electronic circuit design

Biology presents incomparable, but desirable, characteristics compared to engineered systems. Inspired by biological development, we have devised a multi-layered design architecture that attempts to capture the favourable characteristics of biological mechanisms for application to design problems. We have identified and implemented essential features of Genetic Regulatory Networks (GRNs) and cell signalling which lead to self-organization and cell differentiation. We have applied this to electronic circuit design.     

Long-term (trophic) purinergic signalling: purinoceptors control cell proliferation, differentiation and death

The purinergic signalling system, which uses purines and pyrimidines as chemical transmitters, and purinoceptors as effectors, is deeply rooted in evolution and development and is a pivotal factor in cell communication. The ATP and its derivatives function as a ‘danger signal'' in the most primitive forms of life. Purinoceptors are extraordinarily widely distributed in all cell types and tissues and they are involved in the regulation of an even more extraordinary number of biological processes. In addition to fast purinergic signalling in neurotransmission, neuromodulation and secretion, there is long-term (trophic) purinergic signalling involving cell proliferation, differentiation, motility and death in the development and regeneration of most systems of the body. In this article, we focus on the latter in the immune/defence system, in stratified epithelia in visceral organs and skin, embryological development, bone formation and resorption, as well as in cancer.     

Signalling pathways in the pathogenesis of Cryptococcus

Efficient communication with the environment is critical for all living organisms. Fungi utilize complex signalling systems to sense their environments and control proliferation, development and in some cases virulence. Well-studied signalling pathways include the protein kinase A/cyclic AMP (cAMP), protein kinase C (PKC)/mitogen-activated protein kinase (MAPK), lipid signalling cascades, and the calcium–calcineurin signalling pathway. The human pathogenic basidiomycetous fungus Cryptococcus neoformans deploys sensitive signalling systems to survive in the human host, leading to life-threatening meningoencephalitis. Known virulence traits of this fungus, including the antioxidant melanin production, the antiphagocytic polysaccharide capsule and the ability to grow at 37°C, are orchestrated by complex signalling networks, whose understanding is crucial to better treat, diagnose and prevent cryptococcosis.     

Morphological interpretation of darwinism

The development of evolutionary theory requires the resolution of the problem of relationships between random and regular processes in historical development of biological systems. According to the theory of natural selection, ecological factors play a leading role in evolution. Variations are nondirectional, unpredictable, and provide chaotic diversity of variants, only some of which are potentially useful. However, based on random processes, new variants that are useful for organisms and remain adaptive significance in various ecological situations are infrequent. At the same time, morphology demonstrates certain evolutionary patterns. The morphological approach takes into account the role in evolution of structural features of organism and social systems and evolutionary significance of “constructive technologies,” which distinguish morphological interpretation of evolutionary processes. The constructive and evolutionary patterns revealed in biological systems provide the basis for morphological interpretation of the principle of natural selection: both natural and artificial selection is interaction between social systems (populations, ecosystems, biogeocoenoses) and organisms composing them.     

Ca2+ signalling and Ca2+-activated ion channels in exocrine acinar cells

The development of the calcium signalling field, from its early beginnings some 40 years ago to the present, is described. Calcium signalling in exocrine gland acinar cells and the effects of neurotransmitter- or hormone-elicited rises in the cytosolic calcium ion concentration on ion channel gating are reviewed. The highly polarized arrangement of the organelle systems in living acinar cells is described as well as its importance for the physiologically relevant local and polarized calcium signalling events.     

The continuous Sir Philip Sidney game: a simple model of biological signalling.

An analysis of Maynard Smith's two-player, ESS model of biological signalling, the "Sir Philip Sidney game", is presented. The stable strategies of the players in this game are shown to satisfy the conditions of Zahavi's handicap principle. At equilibrium, signals are honest, costly, and costly in a way that is related to the true quality revealed. Further analysis reveals that the level of cost required to maintain stability is inversely related to the degree of relatedness between the players. It therefore seems likely that stable biological signalling systems will feature lower signalling costs when communication occurs between relatives. A three-player, extended version of the model is investigated, in which signals are passed via an intermediate, or "messenger". It is shown that this destabilizes the signalling system, and leads to increased signalling costs. This result suggests that "kin conflict" theories of the evolution of the endosperm in flowering plants require further refinement. The introduction of a novel resource acquisition tissue, which mediates parent-offspring interaction during development, cannot be assumed to limit parent-offspring conflict simply because it carries an extra copy of the maternally inherited genes. The ability to add such complications to the Sir Philip Sidney game and still obtain solutions makes it a very useful modelling tool.     

浅论性状加权

本文从生物分类学理论的一些基本问题分析入手,论述了性状加权的哲学基础和生物学意义,对不同学派的观点从理论上进行了客观分析,并提出了作者本人的一些新的看法。