scholarly journals Bidirectional transfer of Engrailed homeoprotein across the plasma membrane requires PIP2

2020 ◽  
Author(s):  
Irène Amblard ◽  
Edmond Dupont ◽  
Isabel Alves ◽  
Julie Miralvès ◽  
Isabelle Queguiner ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Physiological Function ◽  
Deficient Mutant ◽  
Cellular Mechanisms ◽  
Intercellular Trafficking ◽  
Wide Range ◽  
Common Process ◽  
Summary Statement ◽  
Core Role

1.AbstractHomeoproteins are a class of transcription factors sharing the unexpected property of intercellular trafficking. It confers to homeoproteins a paracrine mode of action, shown to exert a wide range of physiological functions, during development and in the adult. Internalization and secretion, the two steps of intercellular transfer, rely on unconventional mechanisms but the cellular mechanisms at stake still need to be fully characterized. Thanks to the design of new quantitative and sensitive assays dedicated to the study of homeoprotein transfer in cell culture, we demonstrate a core role of the phosphoinositides PIP2 together with cholesterol in the translocation of Engrailed2 (EN2) homeoprotein across the plasma membrane. Both secretion and internalization are regulated according to PIP2 levels, challenged by drug or enzymatic treatments. In addition, EN2 specifically interacts with PIP2 and the reduced affinity of a paracrine deficient mutant of EN2 supports a role of PIP2 in homeoprotein physiological function. We propose that the two ways plasma membrane translocation steps accounting for homeoprotein secretion and internalization respectively are parts of a common process.Summary StatementDeciphering the mechanism of homeoprotein intercellular trafficking

The role of exploratory mechanisms in evolution

1995 ◽  
Vol 349 (1329) ◽  
pp. 297-297
Keyword(s):  
Dynamic Instability ◽  
Specific Mechanism ◽  
Cellular Mechanisms ◽  
Selection Processes ◽  
Wide Range ◽  
Rapid Changes ◽  
Neuronal Processes ◽  
History Of ◽  
Variation And Selection

Many cellular mechanisms use a process of variation and selection to generate specific patterns. Among these, dynamic instability of microtubules has been shown to employ a specific mechanism to intentionally generate variation. In many systems the growth of neurons or neuronal processes is excessive, the final connections being established by stabilization of functional interactions. When changes in neuronal networks take place, such as in metamorphosis, use is made of the plasticity of neuronal connectivity. In the immune system, specific responses are generated by variation and selection. Processes that explore a wide range of conditions and a wide range of structures can be called exploratory processes. These are very robust and capable of responding to damage, variability in the environment and ontogenic changes in the organisms. Such robustness would be useful for adapting to changes that occur during phylogenetic changes as well. Given the extensive history of extinction and radiation in evolution, it may be supposed that these mechanisms have themselves been selected for their capacity to survive rapid changes in the organism and for their ability to generate cellular variation.

scholarly journals Natural Function and Structural Modification of Climacostol, a Ciliate Secondary Metabolite

2020 ◽  
Vol 8 (6) ◽  
pp. 809
Author(s):  
Federico Buonanno ◽  
Elisabetta Catalani ◽  
Davide Cervia ◽  
Cristina Cimarelli ◽  
Enrico Marcantoni ◽  
...  
Keyword(s):  
Chemical Defense ◽  
Secondary Metabolite ◽  
Structural Modification ◽  
Anticancer Agent ◽  
Physiological Function ◽  
Pharmacological Properties ◽  
Ciliated Protozoan ◽  
Natural Function ◽  
Wide Range

The review highlights the main results of two decades of research on climacostol (5-[(2Z)-non-2-en-1-yl]benzene-1,3-diol), the resorcinolic lipid produced and used by the ciliated protozoan Climacostomum virens for chemical defense against a wide range of predators, and to assist its carnivorous feeding. After the first studies on the physiological function of climacostol, the compound and some analogues were chemically synthesized, thus allowing us to explore both its effect on different prokaryotic and eukaryotic biological systems, and the role of its relevant structural traits. In particular, the results obtained in the last 10 years indicate climacostol is an effective antimicrobial and anticancer agent, bringing new clues to the attempt to design and synthesize additional novel analogues that can increase or optimize its pharmacological properties.

scholarly journals The Role of Interleukin-37 in the Pathogenesis of Allergic Diseases

Acta Naturae ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 54-64
Author(s):  
I. P. Shilovskiy ◽  
M. E. Dyneva ◽  
O. M. Kurbacheva ◽  
D. A. Kudlay ◽  
M. R. Khaitov
Keyword(s):  
Allergic Rhinitis ◽  
Atopic Dermatitis ◽  
Bronchial Asthma ◽  
Interleukin 1 ◽  
Allergic Diseases ◽  
Biological Properties ◽  
Negative Regulator ◽  
Cellular Mechanisms ◽  
Wide Range

Cytokines of the interleukin-1 (IL-1) family play an important role in the realization of the protective functions of innate immunity and are the key mediators involved in the pathogenesis of a wide range of diseases, including various manifestations of allergy. The IL-1 family includes more than 11 members. However, the functions of many of them remain to be elucidated. Recently, new members of the IL-1 family have been discovered. In 2000, several independent research groups reported the discovery of a new interleukin of this family, which was named IL-37, or IL-1F7 (according to the new nomenclature). IL-37 was assigned to the IL-1 family based on its structural similarity with other members of this family. The study of its biological properties showed that its activity changes in inflammatory diseases, such as rheumatoid arthritis, psoriasis, as well as allergic diseases (allergic rhinitis, bronchial asthma, and atopic dermatitis). However, unlike most members of the IL-1 family, IL-37 acts as a negative regulator of inflammation. Activation of IL-37 suppresses inflammation, resulting in the suppression of inflammatory cytokines and chemokines, which in turn prevents infiltration of pro-inflammatory cells, mainly eosinophils and neutrophils. The exact molecular and cellular mechanisms of the anti-inflammatory effect of IL-37 in the development of allergic diseases (AD) have not been fully studied. This review summarizes and analyzes the accumulated experimental data on the role of IL-37 in the pathogenesis of AD, such as allergic rhinitis, bronchial asthma, and atopic dermatitis.

scholarly journals PIP3 depletion rescues myoblast fusion defects in human rhabdomyosarcoma cells

2020 ◽  
Author(s):  
Yen-Ling Lian ◽  
Kuan-Wei Chen ◽  
Yu-Ting Chou ◽  
Ting-Ling Ke ◽  
Bi-Chang Chen ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Myoblast Fusion ◽  
Myoblast Differentiation ◽  
Differential Distribution ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Rd Cells ◽  
Summary Statement ◽  
Myogenic Program

AbstractMyoblast fusion is required for myotube formation during myogenesis, and defects in myoblast differentiation and fusion have been implicated in a number of diseases, including human rhabdomyosarcoma. While the transcriptional regulation of the myogenic program has been studied extensively, the mechanisms controlling myoblast fusion remain largely unknown. This study identified and characterized the dynamics of a distinct class of blebs, termed bubbling blebs, which are smaller than those that participate in migration. The formation of these bubbling blebs occurred during differentiation and decreased alongside a decline in phosphatidylinositol-(3,4,5)-trisphosphate (PIP3) at the plasma membrane before myoblast fusion. In a human rhabdomyosarcoma-derived (RD) cell line that exhibits strong blebbing dynamics and myoblast fusion defects, PIP3 was constitutively abundant on the membrane during myogenesis. Targeting phosphatase and tensin homolog (PTEN) to the plasma membrane reduced PIP3 levels, inhibited bubbling blebs, and rescued myoblast fusion defects in RD cells. These findings highlight the differential distribution and crucial role of PIP3 during myoblast fusion and reveal a novel mechanism underlying myogenesis defects in human rhabdomyosarcoma.Summary StatementThis study reveals a novel mechanism underlying myogenesis defects in human rhabdomyosarcoma cells involving PIP3, whose depletion with PTEN rescues myoblast fusion defects.

scholarly journals The Role of Antioxidant Enzymes in the Ovaries

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Shan Wang ◽  
Guolin He ◽  
Meng Chen ◽  
Tao Zuo ◽  
Wenming Xu ◽  
...  
Keyword(s):  
Physiological Function ◽  
Antioxidant Systems ◽  
Oxygen Species ◽  
Female Reproductive System ◽  
Cellular Mechanisms ◽  
Antioxidant Genes ◽  
Reproductive Disease ◽  
Or Genes ◽  
By Products

Proper physiological function of the ovaries is very important for the entire female reproductive system and overall health. Reactive oxygen species (ROS) are generated as by-products during ovarian physiological metabolism, and antioxidants are indicated as factors that can maintain the balance between ROS production and clearance. A disturbance in this balance can induce pathological consequences in oocyte maturation, ovulation, fertilization, implantation, and embryo development, which can ultimately influence pregnancy outcomes. However, our understanding of the molecular and cellular mechanisms underlying these physiological and pathological processes is lacking. This article presents up-to-date findings regarding the effects of antioxidants on the ovaries. An abundance of evidence has confirmed the various significant roles of these antioxidants in the ovaries. Some animal models are discussed in this review to demonstrate the harmful consequences that result from mutation or depletion of antioxidant genes or genes related to antioxidant synthesis. Disruption of antioxidant systems may lead to pathological consequences in women. Antioxidant supplementation is indicated as a possible strategy for treating reproductive disease and infertility by controlling oxidative stress (OS). To confirm this, further investigations are required and more antioxidant therapy in humans has to been performed.

scholarly journals Phototherapy as a Rational Antioxidant Treatment Modality in COVID-19 Management; New Concept and Strategic Approach: Critical Review

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 875
Author(s):  
Reem Hanna ◽  
Snehal Dalvi ◽  
Tudor Sălăgean ◽  
Ioana Roxana Bordea ◽  
Stefano Benedicenti
Keyword(s):  
Critical Review ◽  
Treatment Modality ◽  
Inflammatory Diseases ◽  
Research Question ◽  
Cellular Mechanisms ◽  
Double Blind ◽  
Strategic Approach ◽  
Wide Range ◽  
Promising Treatment

The COVID-19 pandemic has taken the entire globe by storm. The pathogenesis of this virus has shown a cytokine storm release, which contributes to critical or severe multi-organ failure. Currently the ultimate treatment is palliative; however, many modalities have been introduced with effective or minimal outcomes. Meanwhile, enormous efforts are ongoing to produce safe vaccines and therapies. Phototherapy has a wide range of clinical applications against various maladies. This necessitates the exploration of the role of phototherapy, if any, for COVID-19. This critical review was conducted to understand COVID-19 disease and highlights the prevailing facts that link phototherapy utilisation as a potential treatment modality for SARS-CoV-2 viral infection. The results demonstrated phototherapy’s efficacy in regulating cytokines and inflammatory mediators, increasing angiogenesis and enhancing healing in chronic pulmonary inflammatory diseases. In conclusion, this review answered the following research question. Which molecular and cellular mechanisms of action of phototherapy have demonstrated great potential in enhancing the immune response and reducing host–viral interaction in COVID-19 patients? Therefore, phototherapy is a promising treatment modality, which needs to be validated further for COVID-19 by robust and rigorous randomised, double blind, placebo-controlled, clinical trials to evaluate its impartial outcomes and safety.

scholarly journals Tyreoliberin (Trh) – The Regulatory Neuropeptide of Cns Homeostasis

2010 ◽  
Vol 2 (4) ◽  
pp. 139-153 ◽  
Author(s):  
Danuta Jantas
Keyword(s):  
Therapeutic Potential ◽  
Physiological Role ◽  
Cellular Mechanisms ◽  
Current State ◽  
Wide Range ◽  
Locomotive Activity ◽  
Trh Analogues ◽  
Cortical System ◽  
The Brain

SummaryThe physiological role of thyreoliberin (TRH) is the preservation of homeostasis within four systems (i) the hypothalamic-hypophsysiotropic neuroendocrine system, (ii) the brain stem/midbrain/spinal cord system, (iii) the limbic/cortical system, and (iv) the chronobiological system. Thus TRH, via various cellular mechanisms, regulates a wide range of biological processes (arousal, sleep, learning, locomotive activity, mood) and possesses the potential for unique and widespread applications for treatment of human illnesses. Since the therapeutic potential of TRH is limited by its pharmacological profile (enzymatic instability, short half-life, undesirable effects), several synthetic analogues of TRH were constructed and studied in mono- or adjunct therapy of central nervous system (CNS) disturbances. The present article summarizes the current state of understanding of the physiological role of TRH and describes its putative role in clinical indications in CNS maladies with a focus on the action of TRH analogues.

Protein partners of the calcium channel β subunit highlight new cellular functions

2016 ◽  
Vol 473 (13) ◽  
pp. 1831-1844 ◽  
Author(s):  
Mohamad Rima ◽  
Marwa Daghsni ◽  
Ziad Fajloun ◽  
Ridha M'rad ◽  
Juan L. Brusés ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cell Signalling ◽  
Β Subunit ◽  
Cellular Functions ◽  
Excitable Cells ◽  
Functional Roles ◽  
Physiological Processes ◽  
Protein Partners ◽  
Wide Range

Calcium plays a key role in cell signalling by its intervention in a wide range of physiological processes. Its entry into cells occurs mainly via voltage-gated calcium channels (VGCC), which are found not only in the plasma membrane of excitable cells but also in cells insensitive to electrical signals. VGCC are composed of different subunits, α1, β, α2δ and γ, among which the cytosolic β subunit (Cavβ) controls the trafficking of the channel to the plasma membrane, its regulation and its gating properties. For many years, these were the main functions associated with Cavβ. However, a growing number of proteins have been found to interact with Cavβ, emphasizing the multifunctional role of this versatile protein. Interestingly, some of the newly assigned functions of Cavβ are independent of its role in the regulation of VGCC, and thus further increase its functional roles. Based on the identity of Cavβ protein partners, this review emphasizes the diverse cellular functions of Cavβ and summarizes both past findings as well as recent progress in the understanding of VGCC.

The Problem of Identifying and Modeling the Relationship between Monetary Factor and Inflation in the Russian Economy

2008 ◽  
pp. 61-76
Author(s):  
A. Porshakov ◽  
A. Ponomarenko
Keyword(s):  
Money Supply ◽  
Money Demand ◽  
Russian Economy ◽  
Long Run ◽  
Complex Approach ◽  
Wide Range ◽  
Long Time ◽  
The Relationship ◽  
Supply Side Factors

The role of monetary factor in generating inflationary processes in Russia has stimulated various debates in social and scientific circles for a relatively long time. The authors show that identification of the specificity of relationship between money and inflation requires a complex approach based on statistical modeling and involving a wide range of indicators relevant for the price changes in the economy. As a result a model of inflation for Russia implying the decomposition of inflation dynamics into demand-side and supply-side factors is suggested. The main conclusion drawn is that during the recent years the volume of inflationary pressures in the Russian economy has been determined by the deviation of money supply from money demand, rather than by money supply alone. At the same time, monetary factor has a long-run spread over time impact on inflation.

Introduction: Emotion, History and the Arts

2018 ◽  
Vol 7 (2) ◽  
pp. 117-128 ◽  
Author(s):  
Erin Sullivan ◽  
Marie Louise Herzfeld-Schild
Keyword(s):  
Historical Change ◽  
Carson Mccullers ◽  
Emotional Life ◽  
Review Section ◽  
The Arts ◽  
Wide Range ◽  
War Correspondents ◽  
History Of ◽  
Johan Huizinga

This introduction surveys the rise of the history of emotions as a field and the role of the arts in such developments. Reflecting on the foundational role of the arts in the early emotion-oriented histories of Johan Huizinga and Jacob Burkhardt, as well as the concerns about methodological impressionism that have sometimes arisen in response to such studies, the introduction considers how intensive engagements with the arts can open up new insights into past emotions while still being historically and theoretically rigorous. Drawing on a wide range of emotionally charged art works from different times and places—including the novels of Carson McCullers and Harriet Beecher-Stowe, the private poetry of neo-Confucian Chinese civil servants, the photojournalism of twentieth-century war correspondents, and music from Igor Stravinsky to the Beatles—the introduction proposes five ways in which art in all its forms contributes to emotional life and consequently to emotional histories: first, by incubating deep emotional experiences that contribute to formations of identity; second, by acting as a place for the expression of private or deviant emotions; third, by functioning as a barometer of wider cultural and attitudinal change; fourth, by serving as an engine of momentous historical change; and fifth, by working as a tool for emotional connection across communities, both within specific time periods but also across them. The introduction finishes by outlining how the special issue's five articles and review section address each of these categories, while also illustrating new methodological possibilities for the field.

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