The Experts below are selected from a list of 15207 Experts worldwide ranked by ideXlab platform
Julia L Cook - One of the best experts on this subject based on the ideXlab platform.
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noncanonical intracrine action
Journal of The American Society of Hypertension, 2011Co-Authors: Julia L CookAbstract:Over the past 3 decades it has become clear that a large number of extracellular signaling proteins/peptides also act in the Intracellular Space. These factors are termed intracrines and, although diverse in structure, they share a variety of functional features. In recent years, attention has increasingly turned to identifying the Intracellular mechanisms of intracrine action and their implications for human disorders, such as cancer and cardiovascular disease. Perhaps not surprisingly, some intracrines have been shown to bind to and activate their cognate receptors located on Intracellular membranes, such as the nuclear envelope. Here we discuss known intracrine actions and argue that mechanisms distinct from membrane receptor activation (that is, "noncanonical" actions) are often operative and physiologically relevant. These actions, we argue, expand our understanding of peptide signaling in important ways. Moreover, an appreciation of noncanonical intracrine functionality informs our understanding of the major effector protein of the renin-angiotensin system, angiotensin II, as well as other hormones operative in cardiovascular biology.
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senescence apoptosis and stem cell biology the rationale for an expanded view of intracrine action
American Journal of Physiology-heart and Circulatory Physiology, 2009Co-Authors: Julia L CookAbstract:Some extracellular-signaling peptides also at times function within the Intracellular Space. We have termed these peptides intracrines and have argued that intracrine function is associated with a wide variety of peptides/proteins including hormones, growth factors, cytokines, enzymes, and DNA-binding proteins among others. Here we consider the possibility that intracrines participate in the related phenomena of senescence, apoptosis, and stem cell regulation of tissue biology. Based on this analysis, we also suggest that the concept of intracrine action be expanded to include possible regulatory peptide transfer via exosomes/microvesicles and possibly by nanotubes. Moreover, the process of microvesicular and nanotube transfer of peptides and other biologically relevant molecules, which we inclusively term laterality, is explored. These notions have potentially important therapeutic implications, including implications for the therapy of cardiovascular disease.
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the basis of an intracrine pharmacology
The Journal of Clinical Pharmacology, 2008Co-Authors: Julia L CookAbstract:Intracrines are extracellular signaling peptide factors that can act in the Intracellular Space after either internalization or retention in the cells that synthesize them. They are structurally diverse and include hormones, growth factors, enzymes, DNA-binding proteins, and other peptide moieties. We have suggested principles of intracrine action and have applied those principles to forms of cellular and tissue differentiation, hormonal responsiveness, and memory. Moreover, recent findings make clear that some currently available pharmaceuticals act via the alteration of intracrine function. Thus, the beginnings of an intracrine pharmacology are at hand and we here review principles applicable to the design of such agents. The intracrine pharmacology of the renin-angiotensin system, angiogenesis, and stem cell development is discussed.
Vladimir N Uversky - One of the best experts on this subject based on the ideXlab platform.
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liquid liquid phase separation as a common organizing principle of Intracellular Space and biomembranes providing dynamic adaptive responses
Biochimica et Biophysica Acta, 2021Co-Authors: Semen V Nesterov, Nikolay S Ilyinsky, Vladimir N UverskyAbstract:Abstract This work is devoted to the phenomenon of liquid-liquid phase separation (LLPS), which has come to be recognized as fundamental organizing principle of living cells. We distinguish separation processes with different dimensions. Well-known 3D-condensation occurs in aqueous solution and leads to membraneless organelle (MLOs) formation. 2D-films may be formed near membrane surfaces and lateral phase separation (membrane rafts) occurs within the membranes themselves. LLPS may also occur on 1D structures like DNA and the cyto- and nucleoskeleton. Phase separation provides efficient transport and sorting of proteins and metabolites, accelerates the assembly of metabolic and signaling complexes, and mediates stress responses. In this work, we propose a model in which the processes of polymerization (1D structures), phase separation in membranes (2D structures), and LLPS in the volume (3D structures) influence each other. Disordered proteins and whole condensates may provide membrane raft separation or polymerization of specific proteins. On the other hand, 1D and 2D structures with special composition or embedded IDRs can nucleate condensates. We hypothesized that environmental change may trigger a LLPS which can propagate within the cell interior moving along the cytoskeleton or as an autowave. New phase propagation quickly and using a low amount of energy adjusts cell signaling and metabolic systems to new demands. Cumulatively, the interconnected phase separation phenomena in different dimensions represent a previously unexplored system of Intracellular communication and regulation which cannot be ignored when considering both physiological and pathological cell processes.
Werner Streicher - One of the best experts on this subject based on the ideXlab platform.
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liquid demixing of intrinsically disordered proteins is seeded by poly adp ribose
Nature Communications, 2015Co-Authors: Kai John Neelsen, Federico Teloni, Stefania Pellegrino, Merete Grofte, Majbritt Rask, Werner Streicher, Irina Pozdnyakova, Matthias AltmeyerAbstract:Intrinsically disordered proteins can phase separate from the soluble Intracellular Space. Here the authors show that the nucleic acid-mimicking biopolymer poly(ADP-ribose) (PAR) nucleates Intracellular liquid demixing and orchestrates the earliest cellular responses to DNA breakage.
Kazuhisa Ichikawa - One of the best experts on this subject based on the ideXlab platform.
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characterization of cancer Intracellular Space using the k s entropy for images
IEEE Region 10 Conference, 2014Co-Authors: Tuan D Pham, Kazuhisa IchikawaAbstract:Gaining insights into the dynamical mechanisms and information uncertainty underlying complex biological systems has been an exciting and challenging research pursuit in the interplay of theoretical biology, information theory and signal processing. The study is important because such a complex system can be effectively controlled if its dynamical model can be identified. The theory of chaos offers a powerful tool for studying the complexity of nonlinear dynamical systems, and its Kolmogorov-Sinai (K-S) entropy is an important method for distinguishing between different types of data characterizing various behaviors of nonlinear systems. An original model is proposed for estimating K-S entropy of real Intracellular Space. Our findings suggest that the Intracellular Space of the head and neck squamous cell carcinoma SCC61 cell lines is subject to spatial chaos. Such findings can be very useful for the control of spatial parameters involving the modeling and simulation of cancer in spatial cells.
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spatial chaos and complexity in the Intracellular Space of cancer and normal cells
Theoretical Biology and Medical Modelling, 2013Co-Authors: Tuan D Pham, Kazuhisa IchikawaAbstract:One of the most challenging problems in biological image analysis is the quantification of the dynamical mechanism and complexity of the Intracellular Space. This paper investigates potential spatial chaos and complex behavior of the Intracellular Space of typical cancer and normal cell images whose structural details are revealed by the combination of scanning electron microscopy and focused ion beam systems. Such numerical quantifications have important implications for computer modeling and simulation of diseases. Cancer cell lines derived from a human head and neck squamous cell carcinoma (SCC-61) and normal mouse embryonic fibroblast (MEF) cells produced by focused ion beam scanning electron microscopes were used in this study. Spatial distributions of the organelles of cancer and normal cells can be analyzed at both short range and long range of the bounded dynamical system of the image Space, depending on the orientations of the spatial cell. A procedure was designed for calculating the largest Lyapunov exponent, which is an indicator of the potential chaotic behavior in Intracellular images. Furthermore, the sample entropy and regularity dimension were applied to measure the complexity of the Intracellular images. Positive values of the largest Lyapunov exponents (LLEs) of the Intracellular Space of the SCC-61 were obtained in different spatial orientations for both long-range and short-range models, suggesting the chaotic behavior of the cell. The MEF has smaller positive values of LLEs in the long range than those of the SCC-61, and zero vales of the LLEs in the short range analysis, suggesting a non-chaotic behavior. The Intracellular Space of the SCC-61 is found to be more complex than that of the MEF. The degree of complexity measured in the spatial distribution of the Intracellular Space in the diagonal direction was found to be approximately twice larger than the complexity measured in the horizontal and vertical directions. Initial findings are promising for characterizing different types of cells and therefore useful for studying cancer cells in the spatial domain using state-of-the-art imaging technology. The measures of the chaotic behavior and complexity of the spatial cell will help computational biologists gain insights into identifying associations between the oscillation patterns and spatial parameters of cells, and appropriate model for simulating cancer cell signaling networks for cancer treatment and new drug discovery.
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regulation of nf κb oscillation by spatial parameters in true Intracellular Space tics
2013 INTERNATIONAL SYMPOSIUM ON COMPUTATIONAL MODELS FOR LIFE SCIENCES, 2013Co-Authors: Daisuke Ohshima, Hiroshi Sagara, Kazuhisa IchikawaAbstract:Transcription factor NF-κB is activated by cytokine stimulation, viral infection, or hypoxic environment leading to its translocation to the nucleus. The nuclear NF-κB is exported from the nucleus to the cytoplasm again, and by repetitive import and export, NF-κB shows damped oscillation with the period of 1.5-2.0 h. Oscillation pattern of NF-κB is thought to determine the gene expression profile. We published a report on a computational simulation for the oscillation of nuclear NF-κB in a 3D spherical cell, and showed the importance of spatial parameters such as diffusion coefficient and locus of translation for determining the oscillation pattern. Although the value of diffusion coefficient is inherent to protein species, its effective value can be modified by organelle crowding in Intracellular Space. Here we tested this possibility by computer simulation. The results indicate that the effective value of diffusion coefficient is significantly changed by the organelle crowding, and this alters the oscil...
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characterization of cancer and normal Intracellular images by the power law of a fuzzy partition functional
International Conference on Image Analysis and Recognition, 2013Co-Authors: Tuan D Pham, Kazuhisa IchikawaAbstract:The discovery of detailed structures of spatial organelles within a single cell obtained by state-of-the-art molecular imaging technology has provided essential biological information for gaining insights into the study of complex human diseases. In particular, such information is helpful for cancer modeling and simulation. This paper presents a novel concept for characterizing the Intracellular Space of cancer and normal cells using the mathematical principle of power laws applied to a fuzzy partition functional for cluster validity. Experimental results and comparison with image texture analysis suggest the promising application of the proposed method.
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localized activation of proteins in a free Intracellular Space dependence of cellular morphologies and reaction schemes
BioSystems, 2011Co-Authors: Kazuhisa IchikawaAbstract:Localized activation of proteins in a cell is crucial for the segregation of cellular functions leading, for example, to the development of polarized cells and chemotaxis. If there is a physical diffusion barrier, localized activation of proteins will emerge. In case of no physical barrier, however, it is not clear to what extent the protein activation is localized within a three dimensional Intracellular Space. In the previous report we showed a simulation result of localized activation of Ca(2+)/calmodulin-dependent kinase II (CaMKII) within a dendritic spine of a neuron, and this localization was enhanced by the diffusion of calmodulin. However, a dendritic spine will act as a physical diffusion barrier. Here, we report that the localization of activated proteins is seen in more simplified morphology with no diffusion barrier. Furthermore, this localization was seen with a simple reaction scheme. In case that a Ca(2+) source was located at the center of the spherical cell with diameter of 20μm, which is the extreme case without any physical diffusion barrier, the simulation results showed localized activation of a protein around the Ca(2+) source. This localized activation was also enhanced by the diffusion of calmodulin. These localizations were not blurred with time within the tested time range. The reason for the increase in the localization by the diffusion of calmodulin was the replenishment of free calmodulin from surrounding regions. These simulation results indicate that the localized activation of proteins emerges in biological cells without any physical diffusion barrier, and the replenishment of proteins by diffusion can act as an enhancer of localized activation of downstream proteins.
William Margolin - One of the best experts on this subject based on the ideXlab platform.
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bacterial ftsz protein forms phase separated condensates with its nucleoid associated inhibitor slma
EMBO Reports, 2019Co-Authors: Begoña Monterroso, William Margolin, Silvia Zorrilla, Marta Sobrinossanguino, Miguel Angel Roblesramos, Marina Lopezalvarez, Christine D Keating, Germán RivasAbstract:Macromolecular condensation resulting from biologically regulated liquid-liquid phase separation is emerging as a mechanism to organize Intracellular Space in eukaryotes, with broad implications for cell physiology and pathology. Despite their small size, bacterial cells are also organized by proteins such as FtsZ, a tubulin homolog that assembles into a ring structure precisely at the cell midpoint and is required for cytokinesis. Here, we demonstrate that FtsZ can form crowding-induced condensates, reminiscent of those observed for eukaryotic proteins. Formation of these FtsZ-rich droplets occurs when FtsZ is bound to SlmA, a spatial regulator of FtsZ that antagonizes polymerization, while also binding to specific sites on chromosomal DNA. The resulting condensates are dynamic, allowing FtsZ to undergo GTP-driven assembly to form protein fibers. They are sensitive to compartmentalization and to the presence of a membrane boundary in cell mimetic systems. This is a novel example of a bacterial nucleoprotein complex exhibiting condensation into liquid droplets, suggesting that phase separation may also play a functional role in the spatiotemporal organization of essential bacterial processes.
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exploring Intracellular Space function of the min system in round shaped escherichia coli
The EMBO Journal, 2002Co-Authors: Brian D Corbin, William MargolinAbstract:The MinCDE proteins help to select cell division sites in normal cylindrical Escherichia coli by oscillating along the long axis, preventing unwanted polar divisions. To determine how the Min system might function in cells with multiple potential division planes, we investigated its role in a round‐cell rodA mutant. Round cells lacking MinCDE were viable, but growth, morphology and positioning of cell division sites were abnormal relative to Min + cells. In round cells with a long axis, such as those undergoing cell division, green fluorescent protein (GFP) fusions to MinD almost always oscillated parallel to the long axis. However, perfect spheres or irregularly shaped cells exhibited MinD movement to and from multiple sites on the cell surface. A MinE–GFP fusion exhibited similar behavior. These results indicate that the Min proteins can potentially localize anywhere in the cell but tend to move a certain maximum distance from their previous assembly site, thus favoring movement along the cell9s long axis. A new model for the spatial control of division planes by the Min system in round cells is proposed.
