scholarly journals The positive role of noise for information acquisition in biological signaling pathways

2019 ◽  
Author(s):  
Eugenio Azpeitia ◽  
Andreas Wagner
Keyword(s):  
Signaling Pathways ◽  
Molecular Interactions ◽  
Information Acquisition ◽  
Molecular Mechanisms ◽  
Cellular Level ◽  
Living Systems ◽  
Biological Information ◽  
Necessary Condition ◽  
Positive Role ◽  
Wide Range

AbstractAll living systems acquire information about their environment. At the cellular level, they do so through signaling pathways, which rely on interactions between molecules that detect and transmit the presence of an extracellular cue or signal to the cell’s interior. Such interactions are inherently stochastic and thus noisy. In classical information theory, a noisy communication channel degrades the amount of transmissible information relative to a noise-free channel. For this reason, one would expect that the kinetic parameters that determine a pathway’s operation minimize noise. We show that this is not the case under a wide range of biologically sensible parameter values. Specifically, we perform computational simulations of simple signaling systems, which show that a noisy molecular interaction dynamics is a necessary condition for information acquisition. Moreover, we show that optimal information acquisition, where a system reacts most sensitively to changes in the environment, can be obtained close to the maximal attainable level of noise in the system. Our work highlights the positive role that noise can have in biological information processing.Author summaryThe acquisition of information is fundamental for living systems, because the decisions they take based on such information directly affect survival and reproduction. The molecular mechanisms used by cells to acquire information are signaling pathways. The molecular interactions of signaling pathways, such as the binding of a signal to a receptor, are by nature noisy. This is important, because noise disrupts information. Hence, to maximize the acquisition of information, signaling pathways should minimize the noise of their molecular interactions. Here we show that a noisy dynamic of the molecular interactions can improve the acquisition of information, and that the maximal capacity to acquire information can be obtained with a close-to-maximal level of noise in a signaling pathway. Thus, contrary to expectations, noise can improve the acquisition of information in living systems.

scholarly journals Signaling pathways have an inherent need for noise to acquire information

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Eugenio Azpeitia ◽  
Eugenio P. Balanzario ◽  
Andreas Wagner
Keyword(s):  
Signaling Pathways ◽  
Information Acquisition ◽  
Cellular Level ◽  
Kinetic Properties ◽  
Positive Role ◽  
Binding Interactions ◽  
Reversible Binding ◽  
Wide Range ◽  
The One ◽  
Parameter Values

Abstract Background All living systems acquire information about their environment. At the cellular level, they do so through signaling pathways. Such pathways rely on reversible binding interactions between molecules that detect and transmit the presence of an extracellular cue or signal to the cell’s interior. These interactions are inherently stochastic and thus noisy. On the one hand, noise can cause a signaling pathway to produce the same response for different stimuli, which reduces the amount of information a pathway acquires. On the other hand, in processes such as stochastic resonance, noise can improve the detection of weak stimuli and thus the acquisition of information. It is not clear whether the kinetic parameters that determine a pathway’s operation cause noise to reduce or increase the acquisition of information. Results We analyze how the kinetic properties of the reversible binding interactions used by signaling pathways affect the relationship between noise, the response to a signal, and information acquisition. Our results show that, under a wide range of biologically sensible parameter values, a noisy dynamic of reversible binding interactions is necessary to produce distinct responses to different stimuli. As a consequence, noise is indispensable for the acquisition of information in signaling pathways. Conclusions Our observations go beyond previous work by showing that noise plays a positive role in signaling pathways, demonstrating that noise is essential when such pathways acquire information.

scholarly journals Tim-3 enhances FcεRI-proximal signaling to modulate mast cell activation

2015 ◽  
Vol 212 (13) ◽  
pp. 2289-2304 ◽  
Author(s):  
Binh L. Phong ◽  
Lyndsay Avery ◽  
Tina L. Sumpter ◽  
Jacob V. Gorman ◽  
Simon C. Watkins ◽  
...  
Keyword(s):  
T Cells ◽  
Mast Cell ◽  
Signaling Pathways ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Late Phase ◽  
Cell Types ◽  
Mast Cell Activation ◽  
Positive Role ◽  
Ample Evidence

T cell (or transmembrane) immunoglobulin and mucin domain protein 3 (Tim-3) has attracted significant attention as a novel immune checkpoint receptor (ICR) on chronically stimulated, often dysfunctional, T cells. Antibodies to Tim-3 can enhance antiviral and antitumor immune responses. Tim-3 is also constitutively expressed by mast cells, NK cells and specific subsets of macrophages and dendritic cells. There is ample evidence for a positive role for Tim-3 in these latter cell types, which is at odds with the model of Tim-3 as an inhibitory molecule on T cells. At this point, little is known about the molecular mechanisms by which Tim-3 regulates the function of T cells or other cell types. We have focused on defining the effects of Tim-3 ligation on mast cell activation, as these cells constitutively express Tim-3 and are activated through an ITAM-containing receptor for IgE (FcεRI), using signaling pathways analogous to those in T cells. Using a variety of gain- and loss-of-function approaches, we find that Tim-3 acts at a receptor-proximal point to enhance Lyn kinase-dependent signaling pathways that modulate both immediate-phase degranulation and late-phase cytokine production downstream of FcεRI ligation.

scholarly journals STAT3, a Hub Protein of Cellular Signaling Pathways, Is Triggered by β-Hexaclorocyclohexane

2018 ◽  
Vol 19 (7) ◽  
pp. 2108 ◽  
Author(s):  
Elisabetta Rubini ◽  
Fabio Altieri ◽  
Silvia Chichiarelli ◽  
Flavia Giamogante ◽  
Stefania Carissimi ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Cellular Signaling ◽  
Environmental Pollutants ◽  
Altered Expression ◽  
Exposed Population ◽  
Wide Range ◽  
Hepg2 Cell Lines

Background: Organochlorine pesticides (OCPs) are widely distributed in the environment and their toxicity is mostly associated with the molecular mechanisms of endocrine disruption. Among OCPs, particular attention was focused on the effects of β-hexaclorocyclohexane (β-HCH), a widely common pollutant. A detailed epidemiological study carried out on exposed population in the “Valle del Sacco” found correlations between the incidence of a wide range of diseases and the occurrence of β-HCH contamination. Taking into account the pleiotropic role of the protein signal transducer and activator of transcription 3 (STAT3), its function as a hub protein in cellular signaling pathways triggered by β-HCH was investigated in different cell lines corresponding to tissues that are especially vulnerable to damage by environmental pollutants. Materials and Methods: Human prostate cancer (LNCaP), human breast cancer (MCF-7 and MDA-MB 468), and human hepatoma (HepG2) cell lines were treated with 10 μM β-HCH in the presence or absence of specific inhibitors for different receptors. All samples were subjected to analysis by immunoblotting and RT-qPCR. Results and Conclusions: The preliminary results allow us to hypothesize the involvement of STAT3, through both its canonical and non-canonical pathways, in response to β-HCH. Moreover, we ascertained the role of STAT3 as a master regulator of energy metabolism via the altered expression and localization of HIF-1α and PKM2, respectively, resulting in a Warburg-like effect.

scholarly journals Signaling Pathways in Cervical Cancer Chemoresistance: Are microRNAs and Long-Noncoding RNAs the Main Culprits?

2020 ◽  
Author(s):  
Seyyed Reza Mousavi ◽  
Nima Hemmat ◽  
Hossein Bannazadeh Baghi ◽  
Afshin Derakhshani ◽  
Stefania Tommasi ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Drug Resistance ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Bioinformatic Analysis ◽  
Aberrant Expression ◽  
Recurrent Cervical Cancer ◽  
Response To Chemotherapy ◽  
Wide Range ◽  
Non Coding Rnas

Cervical cancer is known as one of the most important cancers in women worldwide. Chemotherapy is a standard treatment for advanced/recurrent cervical cancer in which the prognosis of the disease is really poor and the 1-year survival chance in these patients is maximally 20%. However, resistance to anticancer drugs is a major problem in treating cancer. Cervical cancer stem cells are considered as a fundamental cause of chemo and radio-resistance and also relapse after primary successful treatment. Signaling pathways include a wide range of molecular mechanisms contribute to drug resistance. Recently, microRNAs (miRNAs) are announced as a group of molecular biomarkers involving in response to chemotherapy in cancer patients. As the miRNAs, there are some long non-coding RNAs (LncRNAs) which their aberrant expression is considered as a biomarker for monitoring chemoresistance. In this review, we summarized current reports about the involvement of signaling pathways during chemoresistance in cervical cancer. Then, genes that have been demonstrated their involvement during drug resistance in cervical cancer were tabulated. Further, miRNAs that have been reported as biomarkers during treatment are listed. By bioinformatic analysis, we predictedmiR-335-5p and miR-16-5p as the most potential biomarkers for monitoring resistance to chemotherapy. Finally, long non-coding RNAs that have been introduced in recent studies as novel biomarkers during the response to chemotherapy were mentioned.

scholarly journals From the Ocean to the Lab—Assessing Iron Limitation in Cyanobacteria: An Interface Paper

2020 ◽  
Vol 8 (12) ◽  
pp. 1889
Author(s):  
Annie Vera Hunnestad ◽  
Anne Ilse Maria Vogel ◽  
Evelyn Armstrong ◽  
Maria Guadalupe Digernes ◽  
Murat Van Ardelan ◽  
...  
Keyword(s):  
Inductively Coupled Plasma ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Fluorescence Emission ◽  
Cellular Level ◽  
Iron Limitation ◽  
Inductively Coupled ◽  
Wide Range ◽  
Plasma Mass Spectrometry ◽  
Set Up

Iron is an essential, yet scarce, nutrient in marine environments. Phytoplankton, and especially cyanobacteria, have developed a wide range of mechanisms to acquire iron and maintain their iron-rich photosynthetic machinery. Iron limitation studies often utilize either oceanographic methods to understand large scale processes, or laboratory-based, molecular experiments to identify underlying molecular mechanisms on a cellular level. Here, we aim to highlight the benefits of both approaches to encourage interdisciplinary understanding of the effects of iron limitation on cyanobacteria with a focus on avoiding pitfalls in the initial phases of collaboration. In particular, we discuss the use of trace metal clean methods in combination with sterile techniques, and the challenges faced when a new collaboration is set up to combine interdisciplinary techniques. Methods necessary for producing reliable data, such as High Resolution Inductively Coupled Plasma Mass Spectrometry (HR-ICP-MS), Flow Injection Analysis Chemiluminescence (FIA-CL), and 77K fluorescence emission spectroscopy are discussed and evaluated and a technical manual, including the preparation of the artificial seawater medium Aquil, cleaning procedures, and a sampling scheme for an iron limitation experiment is included. This paper provides a reference point for researchers to implement different techniques into interdisciplinary iron studies that span cyanobacteria physiology, molecular biology, and biogeochemistry.

scholarly journals Molecular mechanisms of cross-talk between growth factors and nuclear receptor signaling

2003 ◽  
Vol 75 (11-12) ◽  
pp. 1743-1756 ◽  
Author(s):  
D. Picard
Keyword(s):  
Growth Factors ◽  
Signaling Pathways ◽  
Nuclear Receptor ◽  
Molecular Mechanisms ◽  
Steroid Receptors ◽  
Reciprocal Relationship ◽  
Signaling Crosstalk ◽  
Intracellular Signals ◽  
Wide Range ◽  
The One

Signaling pathways can be linear, but more complex patterns are common. Growth factors and many other extracellular signals cannot directly enter cells and transduce their information via membrane-bound receptors. In contrast, steroid receptors are members of the nuclear receptor superfamily and await their cognate hormones inside the cells. These two types of signaling pathways are extensively intertwined and crosstalk at many different levels. A wide range of extra- and intracellular signals, including a variety of growth factors, can activate the transcriptional activity of steroid receptors in the absence of their cognate hormones. Conversely, steroid receptors lead a double life. By coupling to signaling molecules that mediate signal transduction of extracellular factors, they can elicit very rapid nongenomic responses. The signaling pathways of steroid-independent activation of steroid receptors, on the one hand, and of nongenomic signaling by steroid receptors, on the other, display a remarkable reciprocal relationship suggesting that these two modes of signaling crosstalk may be two faces of the same coin.

scholarly journals Modelling the molecular mechanisms of aging

2017 ◽  
Vol 37 (1) ◽  
Author(s):  
Mark T. Mc Auley ◽  
Alvaro Martinez Guimera ◽  
David Hodgson ◽  
Neil Mcdonald ◽  
Kathleen M. Mooney ◽  
...  
Keyword(s):  
Aging Process ◽  
Molecular Mechanisms ◽  
Computational Modelling ◽  
Cellular Level ◽  
Wide Range ◽  
Exogenous Factors ◽  
As Stress ◽  
Molecular Damage

The aging process is driven at the cellular level by random molecular damage that slowly accumulates with age. Although cells possess mechanisms to repair or remove damage, they are not 100% efficient and their efficiency declines with age. There are many molecular mechanisms involved and exogenous factors such as stress also contribute to the aging process. The complexity of the aging process has stimulated the use of computational modelling in order to increase our understanding of the system, test hypotheses and make testable predictions. As many different mechanisms are involved, a wide range of models have been developed. This paper gives an overview of the types of models that have been developed, the range of tools used, modelling standards and discusses many specific examples of models that have been grouped according to the main mechanisms that they address. We conclude by discussing the opportunities and challenges for future modelling in this field.

scholarly journals Signaling Pathways That Control Muscle Mass

2020 ◽  
Vol 21 (13) ◽  
pp. 4759 ◽  
Author(s):  
Anna Vainshtein ◽  
Marco Sandri
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathways ◽  
Muscle Mass ◽  
Molecular Mechanisms ◽  
Whole Body ◽  
Control Muscle ◽  
Health And Wellbeing ◽  
Multiple Protein ◽  
Wide Range ◽  
Whole Body Metabolism

The loss of skeletal muscle mass under a wide range of acute and chronic maladies is associated with poor prognosis, reduced quality of life, and increased mortality. Decades of research indicate the importance of skeletal muscle for whole body metabolism, glucose homeostasis, as well as overall health and wellbeing. This tissue’s remarkable ability to rapidly and effectively adapt to changing environmental cues is a double-edged sword. Physiological adaptations that are beneficial throughout life become maladaptive during atrophic conditions. The atrophic program can be activated by mechanical, oxidative, and energetic distress, and is influenced by the availability of nutrients, growth factors, and cytokines. Largely governed by a transcription-dependent mechanism, this program impinges on multiple protein networks including various organelles as well as biosynthetic and quality control systems. Although modulating muscle function to prevent and treat disease is an enticing concept that has intrigued research teams for decades, a lack of thorough understanding of the molecular mechanisms and signaling pathways that control muscle mass, in addition to poor transferability of findings from rodents to humans, has obstructed efforts to develop effective treatments. Here, we review the progress made in unraveling the molecular mechanisms responsible for the regulation of muscle mass, as this continues to be an intensive area of research.

scholarly journals The TGF-β Family: Signaling Pathways, Developmental Roles, and Tumor Suppressor Activities

2002 ◽  
Vol 2 ◽  
pp. 892-925 ◽  
Author(s):  
Aaron N. Johnson ◽  
Stuart J. Newfeld
Keyword(s):  
Tumor Suppressor ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Family Members ◽  
Transforming Growth Factor Β ◽  
Suppressor Activity ◽  
Wide Range ◽  
Tumor Suppressor Activity ◽  
Multicellular Organisms

Intercellular communication is a critical process for all multicellular organisms, and communication among cells is required for proper embryonic development and adult physiology. Members of the Transforming Growth Factor-β (TGF-β) family of secreted proteins communicate information between cells via a complex signaling pathway, and family members are capable of inducing a wide range of cellular responses. The purpose of this review is to provide the reader with a broad introduction to our current understanding of three aspects of the TGF-β family. These are the molecular mechanisms utilized by TGF-β signaling pathways, the developmental roles played by TGF-β family members in a variety of species, and the growing list of cancers in which various TGF-β signaling pathways display tumor suppressor activity.

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