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On Structure and Organization: An Organizing Principle  [PDF]
Nils A. Baas
Mathematics , 2012,
Abstract: We discuss the nature of structure and organization, and the process of making new Things. Hyperstructures are introduced as binding and organizing principles, and we show how they can transfer from one situation to another. A guiding example is the hyperstructure of higher order Brunnian rings and similarly structured many-body systems.
A Protein Turnover Signaling Motif Controls the Stimulus-Sensitivity of Stress Response Pathways  [PDF]
Paul Michael Loriaux,Alexander Hoffmann
PLOS Computational Biology , 2013, DOI: 10.1371/journal.pcbi.1002932
Abstract: Stimulus-induced perturbations from the steady state are a hallmark of signal transduction. In some signaling modules, the steady state is characterized by rapid synthesis and degradation of signaling proteins. Conspicuous among these are the p53 tumor suppressor, its negative regulator Mdm2, and the negative feedback regulator of NFκB, IκBα. We investigated the physiological importance of this turnover, or flux, using a computational method that allows flux to be systematically altered independently of the steady state protein abundances. Applying our method to a prototypical signaling module, we show that flux can precisely control the dynamic response to perturbation. Next, we applied our method to experimentally validated models of p53 and NFκB signaling. We find that high p53 flux is required for oscillations in response to a saturating dose of ionizing radiation (IR). In contrast, high flux of Mdm2 is not required for oscillations but preserves p53 sensitivity to sub-saturating doses of IR. In the NFκB system, degradation of NFκB-bound IκB by the IκB kinase (IKK) is required for activation in response to TNF, while high IKK-independent degradation prevents spurious activation in response to metabolic stress or low doses of TNF. Our work identifies flux pairs with opposing functional effects as a signaling motif that controls the stimulus-sensitivity of the p53 and NFκB stress-response pathways, and may constitute a general design principle in signaling pathways.
Identification of the RGG Box Motif in Shadoo: RNA-Binding and Signaling Roles?
Susan M. Corley,Jill E. Gready
Bioinformatics and Biology Insights , 2008,
Abstract: Using comparative genomics and in-silico analyses, we previously identified a new member of the prion-protein (PrP) family, the gene SPRN, encoding the protein Shadoo (Sho), and suggested its functions might overlap with those of PrP. Extended bioinformatics and conceptual biology studies to elucidate Sho’s functions now reveal Sho has a conserved RGG-box motif, a well-known RNA-binding motif characterized in proteins such as FragileX Mental Retardation Protein. We report a systematic comparative analysis of RGG-box containing proteins which highlights the motif’s functional versatility and supports the suggestion that Sho plays a dual role in cell signaling and RNA binding in brain. These findings provide a further link to PrP, which has well-characterized RNA-binding properties.
RMOD: A Tool for Regulatory Motif Detection in Signaling Network  [PDF]
Jinki Kim, Gwan-Su Yi
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0068407
Abstract: Regulatory motifs are patterns of activation and inhibition that appear repeatedly in various signaling networks and that show specific regulatory properties. However, the network structures of regulatory motifs are highly diverse and complex, rendering their identification difficult. Here, we present a RMOD, a web-based system for the identification of regulatory motifs and their properties in signaling networks. RMOD finds various network structures of regulatory motifs by compressing the signaling network and detecting the compressed forms of regulatory motifs. To apply it into a large-scale signaling network, it adopts a new subgraph search algorithm using a novel data structure called path-tree, which is a tree structure composed of isomorphic graphs of query regulatory motifs. This algorithm was evaluated using various sizes of signaling networks generated from the integration of various human signaling pathways and it showed that the speed and scalability of this algorithm outperforms those of other algorithms. RMOD includes interactive analysis and auxiliary tools that make it possible to manipulate the whole processes from building signaling network and query regulatory motifs to analyzing regulatory motifs with graphical illustration and summarized descriptions. As a result, RMOD provides an integrated view of the regulatory motifs and mechanism underlying their regulatory motif activities within the signaling network. RMOD is freely accessible online at the following URL: http://pks.kaist.ac.kr/rmod.
Microglial Immunoreceptor Tyrosine-Based Activation and Inhibition Motif Signaling in Neuroinflammation  [PDF]
Bettina Linnartz,Yiner Wang,Harald Neumann
International Journal of Alzheimer's Disease , 2010, DOI: 10.4061/2010/587463
Abstract: Elimination of extracellular aggregates and apoptotic neural membranes without inflammation is crucial for brain tissue homeostasis. In the mammalian central nervous system, essential molecules in this process are the Fc receptors and the DAP12-associated receptors which both trigger the microglial immunoreceptor tyrosine-based activation motif- (ITAM-) Syk-signaling cascade. Microglial triggering receptor expressed on myeloid cells-2 (TREM2), signal regulatory protein- 1, and complement receptor-3 (CD11b/CD18) signal via the adaptor protein DAP12 and activate phagocytic activity of microglia. Microglial ITAM-signaling receptors are counter-regulated by immunoreceptor tyrosine-based inhibition motif- (ITIM-) signaling molecules such as sialic acid-binding immunoglobulin superfamily lectins (Siglecs). Siglecs can suppress the proinflammatory and phagocytic activity of microglia via ITIM signaling. Moreover, microglial neurotoxicity is alleviated via interaction of Siglec-11 with sialic acids on the neuronal glycocalyx. Thus, ITAM- and ITIM-signaling receptors modulate microglial phagocytosis and cytokine expression during neuroinflammatory processes. Their dysfunction could lead to impaired phagocytic clearance and neurodegeneration triggered by chronic inflammation. 1. Microglia and Alzheimer’s Disease Microglial cells originate from myeloid cells of the hematopoietic lineage and are the resident immune cells of the central nervous system (CNS). They are involved in the active immune defense by their ability to phagocytose invading bacteria and to release reactive oxygen species acting as microbicides. In the healthy brain, microglia are relative evenly distributed and predominantly found in a so-called “resting” state, displaying a small cell body with many highly branched processes, which are highly motile and continuously monitor the brain parenchyma [1–3]. Microglia are involved in tissue maintenance, execution of innate immunity, and participation in adaptive immune responses [1–3]. They are regarded as active sensors, searching for and reading biochemical signals of pathogenic changes in the brain environment [2]. In response to injury, ischemia and inflammatory stimuli microglia change from an immunologically silent state to an activated state that is reflected in different morphological appearance - amoeboid, rodlike, or phagocytic. They can migrate to the site of disturbance, secrete a wide range of soluble factors including cytokines as well as neurotrophic factors, and phagocytose cellular debris. Thereby, microglia contribute to tissue
The Application of Visual Organization Principle in the Detection of Sleep Spindles  [PDF]
Xuemei Jin, Junzhong Zou, Jian Zhang
Journal of Biomedical Science and Engineering (JBiSE) , 2017, DOI: 10.4236/jbise.2017.105B001
In order to detect the sleep spindles simply and efficiently, a novel time-domain approach to detect sleep spindles based on the principles of visual organization is proposed. The code idea of the visual organization is to organize the primary visual elements according to some rules of organization, and to form a more meaningful object of visual processing, as the input of next process. After the collected EEG is processed with the merging algorithm based on the principle of visual organization, it can extract the time-domain feature frequency and duration time better. Use these features with a simple algorithm to detect spindles achieving sensitivity of 92.5% and specificity of 98.1%, which verifies the validity of this method to detect the sleep spindles.
Unraveling plant hormone signaling through the use of small molecules  [PDF]
Adeline Rigal,Qian Ma,Stéphanie Robert
Frontiers in Plant Science , 2014, DOI: 10.3389/fpls.2014.00373
Abstract: Plants have acquired the capacity to grow continuously and adjust their morphology in response to endogenous and external signals, leading to a high architectural plasticity. The dynamic and differential distribution of phytohormones is an essential factor in these developmental changes. Phytohormone perception is a fast but complex process modulating specific developmental reprogramming. In recent years, chemical genomics or the use of small molecules to modulate target protein function has emerged as a powerful strategy to study complex biological processes in plants such as hormone signaling. Small molecules can be applied in a conditional, dose-dependent and reversible manner, with the advantage of circumventing the limitations of lethality and functional redundancy inherent to traditional mutant screens. High-throughput screening of diverse chemical libraries has led to the identification of bioactive molecules able to induce plant hormone-related phenotypes. Characterization of the cognate targets and pathways of those molecules has allowed the identification of novel regulatory components, providing new insights into the molecular mechanisms of plant hormone signaling. An extensive structure-activity relationship (SAR) analysis of the natural phytohormones, their designed synthetic analogs and newly identified bioactive molecules has led to the determination of the structural requirements essential for their bioactivity. In this review, we will summarize the so far identified small molecules and their structural variants targeting specific phytohormone signaling pathways. We will highlight how the SAR analyses have enabled better interrogation of the molecular mechanisms of phytohormone responses. Finally, we will discuss how labeled/tagged hormone analogs can be exploited, as compelling tools to better understand hormone signaling and transport mechanisms.
Unraveling the signaling and signal transduction mechanisms controlling arbuscular mycorrhiza development
Lambais, Marcio Rodrigues;
Scientia Agricola , 2006, DOI: 10.1590/S0103-90162006000400013
Abstract: arbuscular mycorrhiza (am) are the most widespread symbiotic associations between plant roots and soil fungi. am can contribute to increasing the survival and fitness of plants to limiting environments mostly due to their ability in improving nutrient uptake from the soil solution. despite their ecological significance, the mechanisms controlling am development and functioning are largely unknown. the obligate mutualistic nature of the arbuscular mycorrhizal fungi (amf) has hampered the advances on the understanding and application of the symbiosis. significant alterations in the genetic programs of both symbionts are required for the successful establishment of an am, and complex signaling and signal transduction mechanisms are likely involved. the analyses of legume mutants affected in the development of nitrogen fixing nodules and am suggest that part of the signal transduction pathways involved in the regulation of both symbioses are conserved. even though the use of genomics of model plants has helped to advance our understanding of the regulatory mechanisms in am, identifying the signal molecules involved in plant-amf communication and determining their transduction pathways is still essential for its biotechnological application in agriculture.
Unraveling the Relationship between Employees’ Perception to Organization and Turnover Intentions: Exploring the Mediating Effects of Trust to Organization  [cached]
Belal Al-Sakarnah,Faleh Abdelgader Alhawary
International Journal of Business and Management , 2009, DOI: 10.5539/ijbm.v4n10p177
Abstract: Staff turnover is a serious issue in the field of human resources management, Organizations of all kind must pay more attention to this phenomenon and must not be overlooked, so it is important to understand their needs and be able to satisfy it in order to reduce or may be strongly control the turnover. This study therefore was conducted to examine the main effects of employees’ perceived organizational support and external prestige on their turnover intentions, with the mediating effects of their trust to organization. Questionnaire was designed and administered to collect data from sample of 402 employees of various levels selected from different insurance companies in Jordan. The study findings show that employees with higher level of perceived organizational support and perceived external prestige may have higher level of trust towards the management of their company, and hence, less likely to leave the firm. Therefore, the key to maintain a stable workforce is to make employees perceive the support from the company, and become proud of their company. The direct and indirect effects of these constructs on turnover intention are analyzed by structural equation modeling (SEM). The findings of this study will assist top management in business organizations to better deal with the phenomena of staff turnover, finally, the limitations of the study, directions for future research, and implications of the results are discussed.
Local PT symmetry violates the no-signaling principle  [PDF]
Yi-Chan Lee,Min-Hsiu Hsieh,Steven T. Flammia,Ray-Kuang Lee
Physics , 2013, DOI: 10.1103/PhysRevLett.112.130404
Abstract: Bender et al. have developed PT-symmetric quantum theory as an extension of quantum theory to non-Hermitian Hamiltonians. We show that when this model has a local PT symmetry acting on composite systems it violates the non-signaling principle of relativity. Since the case of global PT symmetry is known to reduce to standard quantum mechanics, this shows that the PT-symmetric theory is either a trivial extension or likely false as a fundamental theory.
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