scholarly journals The Evolving Roles of Cardiac Macrophages in Homeostasis, Regeneration, and Repair

2021 ◽  
Vol 22 (15) ◽  
pp. 7923
Author(s):  
Santiago Alvarez-Argote ◽  
Caitlin C. O’Meara
Keyword(s):  
Cardiac Injury ◽  
Cardiac Regeneration ◽  
Normal Function ◽  
Cardiac Conduction ◽  
Cell Detection ◽  
Fate Mapping ◽  
The Novel ◽  
Functional Roles ◽  
Macrophage Populations ◽  
And Function

Macrophages were first described as phagocytic immune cells responsible for maintaining tissue homeostasis by the removal of pathogens that disturb normal function. Historically, macrophages have been viewed as terminally differentiated monocyte-derived cells that originated through hematopoiesis and infiltrated multiple tissues in the presence of inflammation or during turnover in normal homeostasis. However, improved cell detection and fate-mapping strategies have elucidated the various lineages of tissue-resident macrophages, which can derive from embryonic origins independent of hematopoiesis and monocyte infiltration. The role of resident macrophages in organs such as the skin, liver, and the lungs have been well characterized, revealing functions well beyond a pure phagocytic and immunological role. In the heart, recent research has begun to decipher the functional roles of various tissue-resident macrophage populations through fate mapping and genetic depletion studies. Several of these studies have elucidated the novel and unexpected roles of cardiac-resident macrophages in homeostasis, including maintaining mitochondrial function, facilitating cardiac conduction, coronary development, and lymphangiogenesis, among others. Additionally, following cardiac injury, cardiac-resident macrophages adopt diverse functions such as the clearance of necrotic and apoptotic cells and debris, a reduction in the inflammatory monocyte infiltration, promotion of angiogenesis, amelioration of inflammation, and hypertrophy in the remaining myocardium, overall limiting damage extension. The present review discusses the origin, development, characterization, and function of cardiac macrophages in homeostasis, cardiac regeneration, and after cardiac injury or stress.

scholarly journals Vertebrate cardiac regeneration: evolutionary and developmental perspectives

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Stephen Cutie ◽  
Guo N. Huang
Keyword(s):  
Cardiac Injury ◽  
Adaptive Immune System ◽  
Cardiac Regeneration ◽  
Heart Regeneration ◽  
Adaptive Immune ◽  
Selective Pressures ◽  
Trade Offs ◽  
Lower Vertebrates ◽  
Complex Adaptive ◽  
And Function

AbstractCardiac regeneration is an ancestral trait in vertebrates that is lost both as more recent vertebrate lineages evolved to adapt to new environments and selective pressures, and as members of certain species developmentally progress towards their adult forms. While higher vertebrates like humans and rodents resolve cardiac injury with permanent fibrosis and loss of cardiac output as adults, neonates of these same species can fully regenerate heart structure and function after injury – as can adult lower vertebrates like many teleost fish and urodele amphibians. Recent research has elucidated several broad factors hypothesized to contribute to this loss of cardiac regenerative potential both evolutionarily and developmentally: an oxygen-rich environment, vertebrate thermogenesis, a complex adaptive immune system, and cancer risk trade-offs. In this review, we discuss the evidence for these hypotheses as well as the cellular participators and molecular regulators by which they act to govern heart regeneration in vertebrates.

Abstract P325: The Role Of Runx1 In Cardiomyocyte Cell Cycle And Ploidy

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Samantha K Swift ◽  
Michaela Patterson
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Heart Development ◽  
Cardiac Injury ◽  
Cardiac Regeneration ◽  
Cardiac Conduction ◽  
Calcium Handling ◽  
Mouse Heart ◽  
Disease States ◽  
Eccentric Hypertrophy

Adult mammalian cardiomyocytes (CMs) are thought to be post-mitotic and therefore unable to regenerate the myocardium after injury. In recent years various studies have shown that the adult mammalian CM is capable of a small amount of proliferation, potentially restricted to a subset of CMs. One such study demonstrated that having greater percentages of the rare mononuclear diploid cardiomyocyte (MNDCM) is associated with improved outcomes after myocardial infarction (MI). An accompanying genome-wide association analysis identified genetic loci associated with the frequency of the MNDCM population. One candidate to come out of this screen was Runx1. Concurrently, RUNX1 captured the attention of cardiac regeneration researchers due to its increased presence in disease states, with some suggesting it may be a marker for dedifferentiation (fetal gene induction). One recent study demonstrated improved calcium handling and decreased eccentric hypertrophy following RUNX1 ablation after injury, perhaps corroborating the idea that RUNX1 is involved with CM dedifferentiation. We hypothesize that Runx1 influences dedifferentiation in CMs, impacting ploidy, as well as CM cell cycle activity and post-MI outcomes. We found that CM-specific overexpression (OE) of Runx1 results in a doubling of the MNDCM population, thereby validating its influence on the population. Via multiple contexts including postnatal development and adult injury, knocking out Runx1 decreases DNA synthesis while Runx1 OE increases DNA synthesis. Furthermore, an initial analysis of RNAseq data demonstrates that RUNX1 OE in a neonatal mouse hearts demonstrated differential expression in genes related to cardiac conduction, contraction, heart development, regeneration, and regulation of cell differentiation . After MI in the adult mouse heart, the effects of Runx1 OE resulted in transient benefits which included increased cell cycle activity and preservation of function. These data suggest that Runx1 is not simply a marker of CM dedifferentiation, but also a regulator of the process including cell cycle activation. Ongoing work will tease apart this role in more detail and could establish RUNX1 as a prominent therapeutic target for mitigating effects of cardiac injury.

Computational Approaches to Predict the Non-canonical DNAs

2019 ◽  
Vol 14 (6) ◽  
pp. 470-479 ◽  
Author(s):  
Nazia Parveen ◽  
Amen Shamim ◽  
Seunghee Cho ◽  
Kyeong Kyu Kim
Keyword(s):  
Computational Methods ◽  
Genetic Instability ◽  
Computational Prediction ◽  
Structure And Function ◽  
Sequence Motifs ◽  
Computational Approaches ◽  
Functional Roles ◽  
And Function ◽  
Genetic Events ◽  
Insight Into

Background: Although most nucleotides in the genome form canonical double-stranded B-DNA, many repeated sequences transiently present as non-canonical conformations (non-B DNA) such as triplexes, quadruplexes, Z-DNA, cruciforms, and slipped/hairpins. Those noncanonical DNAs (ncDNAs) are not only associated with many genetic events such as replication, transcription, and recombination, but are also related to the genetic instability that results in the predisposition to disease. Due to the crucial roles of ncDNAs in cellular and genetic functions, various computational methods have been implemented to predict sequence motifs that generate ncDNA. Objective: Here, we review strategies for the identification of ncDNA motifs across the whole genome, which is necessary for further understanding and investigation of the structure and function of ncDNAs. Conclusion: There is a great demand for computational prediction of non-canonical DNAs that play key functional roles in gene expression and genome biology. In this study, we review the currently available computational methods for predicting the non-canonical DNAs in the genome. Current studies not only provide an insight into the computational methods for predicting the secondary structures of DNA but also increase our understanding of the roles of non-canonical DNA in the genome.

Functional Roles of Chelated Magnesium Ions in RNA Folding and Function

Biochemistry ◽  
2021 ◽  
Author(s):  
Ryota Yamagami ◽  
Jacob P. Sieg ◽  
Philip C. Bevilacqua
Keyword(s):  
Rna Folding ◽  
Magnesium Ions ◽  
Functional Roles ◽  
And Function

scholarly journals Roles of the novel coiled-coil protein Rng10 in septum formation during fission yeast cytokinesis

2016 ◽  
Vol 27 (16) ◽  
pp. 2528-2541 ◽  
Author(s):  
Yajun Liu ◽  
I-Ju Lee ◽  
Mingzhai Sun ◽  
Casey A. Lower ◽  
Kurt W. Runge ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Rho Gtpases ◽  
Cellular Localization ◽  
Affinity Purification ◽  
Coiled Coil ◽  
The Novel ◽  
Septum Formation ◽  
Division Site ◽  
And Function

Rho GAPs are important regulators of Rho GTPases, which are involved in various steps of cytokinesis and other processes. However, regulation of Rho-GAP cellular localization and function is not fully understood. Here we report the characterization of a novel coiled-coil protein Rng10 and its relationship with the Rho-GAP Rga7 in fission yeast. Both rng10Δ and rga7Δ result in defective septum and cell lysis during cytokinesis. Rng10 and Rga7 colocalize on the plasma membrane at the cell tips during interphase and at the division site during cell division. Rng10 physically interacts with Rga7 in affinity purification and coimmunoprecipitation. Of interest, Rga7 localization is nearly abolished without Rng10. Moreover, Rng10 and Rga7 work together to regulate the accumulation and dynamics of glucan synthases for successful septum formation in cytokinesis. Our results show that cellular localization and function of the Rho-GAP Rga7 are regulated by a novel protein, Rng10, during cytokinesis in fission yeast.

Bioerodible Polypyrrole

2001 ◽  
Vol 711 ◽  
Author(s):  
Alexander Zelikin ◽  
Venkatram Shastri ◽  
David Lynn ◽  
Jian Farhadi ◽  
Ivan Martin ◽  
...  
Keyword(s):  
Erosion Rate ◽  
Acid Group ◽  
The Novel ◽  
Carboxylic Acid Group ◽  
Polymer Backbone ◽  
Cellular Processes ◽  
Novel Approach ◽  
Efficient Control ◽  
And Function ◽  
Substrate Independent

ABSTRACTConductive polymers such as polypyrrole (Ppy) are potentially useful as an active interface for altering cellular processes and function. Their utilization in medically related applications however have been substantially held back by their non-degradable nature. Herein we report a novel approach to creation of bioerodible polypyrroles via modification of pyrrole beta-carbon with an ionizable moiety. It has been shown that the erosion rate of acid-bearing derivative of polypyrrole increases with pH, which is consistent with the pH dependent ionization of carboxylic acid group. The novel paradigm proposed for the creation of bioerodible polypyrroles allows for simple and efficient control over the erosion rate of the substrate independent of the polymer chain length, via the choice of the terminal ionizable group and its concentration along the polymer backbone.

Poetics of literary dream in Sigizmund Krzhizhanovsky’s novel “Sideline”

2021 ◽  
pp. 132-143
Author(s):  
M. A. Lipina ◽  
Keyword(s):  
Literary Criticism ◽  
Structural Model ◽  
Sudden Change ◽  
The Novel ◽  
Psychological Function ◽  
Symbolic Function ◽  
Original Idea ◽  
Falling Asleep ◽  
And Function ◽  
The City

The paper is dedicated to studying the oneiric text of S. Krzhizhanovsky’s novel “Sideline.” The topicality of the research is due to modern literary criticism interest in examining various aspects of artistic hypnology of Russian writers, as well as studying the works of “returned” authors, including S. Krzhizhanovsky. The realization specifics of the structural model of the literary dream in question can be presented as the following scheme: unconscious falling asleep – dream-journey – awakening by falling down. Different variants of artistic implementation of the main metaphors connected with dreaming are analyzed: “dream-life” in the image of briefcase-cushion and the image of “million-brained” dream of equality and brotherhood; “dream-death” in the image of the leader of a dream world, with the prevalence of thanatological vocabulary in the description of the city of dreams. The ways of imitating the space of real dreaming in the oneiric text of the novel are studied: awakening by falling, sudden muteness of characters, sudden change of location, etc. Also, the specifics of using the plot device of an unannounced dream is considered contributing to the illusion of “reality” of everything that happens to the character in the city of dreams. An attempt is made to consider the oneirotop of the novel in terms of classification by genre and function, plot and composition, images and esthetics and characters, as well as artistic functions of dreams in the literature (plot function, psychological function, idea, and symbolic function). The oneiric text of Krzhizhanosky’s novel “Sideline” is viewed as an artistic realization of the author’s original idea of the subconscious, dreamy origin of a communist utopia.

scholarly journals Anisotropic Cardiac Conduction

2020 ◽  
Vol 9 (4) ◽  
pp. 202-210
Author(s):  
Irum Kotadia ◽  
John Whitaker ◽  
Caroline Roney ◽  
Steven Niederer ◽  
Mark O’Neill ◽  
...  
Keyword(s):  
Gap Junction ◽  
Cardiac Tissue ◽  
Diffusion Tensor ◽  
Interstitial Fibrosis ◽  
Cardiac Conduction ◽  
Principal Mechanism ◽  
Disease States ◽  
And Function ◽  
Anisotropic Conduction

Anisotropy is the property of directional dependence. In cardiac tissue, conduction velocity is anisotropic and its orientation is determined by myocyte direction. Cell shape and size, excitability, myocardial fibrosis, gap junction distribution and function are all considered to contribute to anisotropic conduction. In disease states, anisotropic conduction may be enhanced, and is implicated, in the genesis of pathological arrhythmias. The principal mechanism responsible for enhanced anisotropy in disease remains uncertain. Possible contributors include changes in cellular excitability, changes in gap junction distribution or function and cellular uncoupling through interstitial fibrosis. It has recently been demonstrated that myocyte orientation may be identified using diffusion tensor magnetic resonance imaging in explanted hearts, and multisite pacing protocols have been proposed to estimate myocyte orientation and anisotropic conduction in vivo. These tools have the potential to contribute to the understanding of the role of myocyte disarray and anisotropic conduction in arrhythmic states.

scholarly journals A developmental biologist’s journey to rediscover the Zen of plant physiology

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 264 ◽  
Author(s):  
José R. Dinneny
Keyword(s):  
Plant Physiology ◽  
Human Population ◽  
Holistic Approach ◽  
Normal Function ◽  
Plant Biology ◽  
Form And Function ◽  
Adaptive Mechanisms ◽  
Basic Concepts ◽  
Living Organisms ◽  
And Function

Physiology, which is often viewed as a field of study distinct from development, is technically defined as the branch of biology that explores the normal function of living organisms and their parts. Because plants normally develop continuously throughout their life, plant physiology actually encompasses all developmental processes. Viewing plant biology from a physiologist’s perspective is an attempt to understand the interconnectedness of development, form, and function in the context of multidimensional complexity in the environment. To meet the needs of an expanding human population and a degrading environment, we must understand the adaptive mechanisms that plants use to acclimate to environmental change, and this will require a more holistic approach than is used by current molecular studies. Grand challenges for studies on plant physiology require a more sophisticated understanding of the environment that plants grow in, which is likely to be at least as complex as the plant itself. Moving the lab to the field and using the field for inspiration in the lab need to be expressly promoted by the community as we work to apply the basic concepts learned through reductionist approaches toward a more integrated and realistic understanding of the plant.

scholarly journals p38δ genetic ablation protects female mice from anthracycline cardiotoxicity

2020 ◽  
Author(s):  
Sharon A George ◽  
Alexi Kiss ◽  
Sofian N Obaid ◽  
Aileen Venegas ◽  
Trisha Talapatra ◽  
...  
Keyword(s):  
Cardiac Injury ◽  
Mapk Signaling ◽  
Anthracycline Cardiotoxicity ◽  
Genetic Ablation ◽  
Female Mice ◽  
Echocardiographic Parameters ◽  
The Individual ◽  
And Function ◽  
First Time ◽  
Dose Dependent

ABSTRACTBACKGROUNDThe efficacy of an anthracycline antibiotic doxorubicin (DOX) as a chemotherapeutic agent is limited by dose-dependent cardiotoxicity. DOX is associated with activation of intracellular stress signaling pathways including p38 MAPKs. While previous studies have implicated p38 MAPK signaling in DOX-induced cardiac injury, the roles of the individual p38 isoforms, specifically, of the alternative isoforms p38γ and p38δ, remain uncharacterized.OBJECTIVESTo determine the potential cardioprotective effects of p38γ and p38δ genetic deletion in mice subjected to acute DOX treatment.METHODSMale and female wild-type (WT), p38γ-/-, p38δ-/- and p38γ-/-δ-/- mice were injected with 30 mg/kg DOX and their survival was tracked for ten days. During this period cardiac function was assessed by echocardiography and electrocardiography and fibrosis by PicroSirius Red staining. Immunoblotting was performed to assess the expression of signaling proteins and markers linked to autophagy.RESULTSSignificantly improved survival was observed in p38δ-/- female mice post-DOX relative to WT females, but not in p38γ-/- or p38γ-/-δ-/- male or female mice. The improved survival in DOX-treated p38δ-/- females was associated with decreased fibrosis, increased cardiac output and LV diameter relative to DOX-treated WT females, and similar to saline-treated controls. Structural and echocardiographic parameters were either unchanged or worsened in all other groups. Increased autophagy, as evidenced by increased LC3-II level, and decreased mTOR activation was also observed in DOX-treated p38δ-/- females.CONCLUSIONSp38δ plays a crucial role in promoting DOX-induced cardiotoxicity in female mice by inhibiting autophagy. Therefore, p38δ targeting could be a potential cardioprotective strategy in anthracycline chemotherapy.NEW AND NOTEWORTHYThis study for the first time identifies the roles of the alternative p38γ and p38δ MAPK isoforms in promoting DOX-cardiotoxicity in a sex-specific manner. While p38γ systemic deletion did not affect DOX-cardiotoxicity, p38δ systemic deletion was cardioprotective in female but not in male mice. Cardiac structure and function were preserved in DOX-treated p38δ-/- females and autophagy was increased.

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