scholarly journals Next-generation pacemakers: from electrical devices to biological pacemakers

2021 ◽  
Vol 102 (6) ◽  
pp. 916-922
Author(s):  
V N Oslopov ◽  
A Kh Mamedova ◽  
D N Nafeeva ◽  
E V Khazova ◽  
Yu V Oslopova
Keyword(s):  
Ion Channels ◽  
Hybrid Approach ◽  
Cardiac Conduction ◽  
High Tech ◽  
Direct Stimulation ◽  
Cardiac Stimulation ◽  
Advantages And Disadvantages ◽  
Small Series ◽  
Genes Encoding ◽  
Biological Pacemaker

The invention of an electric pacemaker in the middle of the 20th century led to a revolution in the treatment of cardiac conduction system diseases. The improvement of pacemakers continued. In 1962, the first small series of external pacemakers for percutaneous and direct stimulation was produced in Kaunas. After a while, electric pacemakers became more reliable, smaller and lighter in weight, but the problem of foreign body associated infection and limited service life remained unresolved. Modern high-tech medicine strives to create less invasive electric pacemakers, but nevertheless, biological pacemakers can expand the therapeutic arsenal for the treatment of cardiac patients, being the most physiological for humans. The concept of an artificial biological pacemaker consists of the creation of an organic structure that generates a spontaneous rhythm from the implantation site in the myocardium. Various gene and cellular approaches were used to create biological pacemakers: a functional reorganization approach (use of adenovirus vectors for hyperexpression of genes encoding ion channels in cardiomyocytes); hybrid approach (use of fibroblasts to deliver genes of ion channels that provide heart automation); somatic reprogramming approach (overexpression of the transcription factor TBX18 using adenoviral vectors, which reprograms cardiomyocytes into induced sinoatrial node cells, creating cardiac stimulatory activity); cellular approach (transplantation of stem cells to a specific place in the heart, thereby creating biological stimulation). Modern methods of electrical cardiac stimulation and the developed concepts of the biological pacemaker clearly show the possibility of eliminating current problems associated with the use of an artificial pacemaker by replacing it with a biological one. Each of the approaches (gene, cellular, hybrid-cellular, somatic reprogramming) has its own advantages and disadvantages, which predisposes to further study and improvement in order to introduce a biological pacemaker into clinical practice.

Extraction of Auditory Information by Modulation of Neuronal Ion Channels

2018 ◽  
pp. 272-300
Author(s):  
Leonard K. Kaczmarek
Keyword(s):  
Ion Channels ◽  
Neuronal Firing ◽  
Auditory Information ◽  
Auditory Neurons ◽  
Complex Sound ◽  
Medial Nucleus ◽  
Rapid Changes ◽  
Genes Encoding ◽  
Kinetics Of ◽  
Trapezoid Body

All neurons express a subset of over seventy genes encoding potassium channel subunits. These channels have been studied in auditory neurons, particularly in the medial nucleus of the trapezoid body. The amplitude and kinetics of various channels in these neurons can be modified by the auditory environment. It has been suggested that such modulation is an adaptation of neuronal firing patterns to specific patterns of auditory inputs. Alternatively, such modulation may allow a group of neurons, all expressing the same set of channels, to represent a variety of responses to the same pattern of incoming stimuli. Such diversity would ensure that a small number of genetically identical neurons could capture and encode many aspects of complex sound, including rapid changes in timing and amplitude. This review covers the modulation of ion channels in the medial nucleus of the trapezoid body and how it may maximize the extraction of auditory information.All neurons express a subset of over seventy genes encoding potassium channel subunits. These channels have been studied in auditory neurons, particularly in the medial nucleus of the trapezoid body. The amplitude and kinetics of various channels in these neurons can be modified by the auditory environment. It has been suggested that such modulation is an adaptation of neuronal firing patterns to specific patterns of auditory inputs. Alternatively, such modulation may allow a group of neurons, all expressing the same set of channels, to represent a variety of responses to the same pattern of incoming stimuli. Such diversity would ensure that a small number of genetically identical neurons could capture and encode many aspects of complex sound, including rapid changes in timing and amplitude. This review covers the modulation of ion channels in the medial nucleus of the trapezoid body and how it may maximize the extraction of auditory information.

Acute O2 sensing through HIF2α-dependent expression of atypical cytochrome oxidase subunits in arterial chemoreceptors

2019 ◽  
Vol 13 (615) ◽  
pp. eaay9452 ◽  
Author(s):  
Alejandro Moreno-Domínguez ◽  
Patricia Ortega-Sáenz ◽  
Lin Gao ◽  
Olalla Colinas ◽  
Paula García-Flores ◽  
...  
Keyword(s):  
Ion Channels ◽  
Carotid Body ◽  
Acute Hypoxia ◽  
Mechanistic Explanation ◽  
Nerve Fibers ◽  
Adaptive Responses ◽  
Glomus Cells ◽  
Adult Mice ◽  
Genes Encoding ◽  
Regulation Of Breathing

Acute cardiorespiratory responses to O2 deficiency are essential for physiological homeostasis. The prototypical acute O2-sensing organ is the carotid body, which contains glomus cells expressing K+ channels whose inhibition by hypoxia leads to transmitter release and activation of nerve fibers terminating in the brainstem respiratory center. The mechanism by which changes in O2 tension modulate ion channels has remained elusive. Glomus cells express genes encoding HIF2α (Epas1) and atypical mitochondrial subunits at high levels, and mitochondrial NADH and reactive oxygen species (ROS) accumulation during hypoxia provides the signal that regulates ion channels. We report that inactivation of Epas1 in adult mice resulted in selective abolition of glomus cell responsiveness to acute hypoxia and the hypoxic ventilatory response. Epas1 deficiency led to the decreased expression of atypical mitochondrial subunits in the carotid body, and genetic deletion of Cox4i2 mimicked the defective hypoxic responses of Epas1-null mice. These findings provide a mechanistic explanation for the acute O2 regulation of breathing, reveal an unanticipated role of HIF2α, and link acute and chronic adaptive responses to hypoxia.

scholarly journals Regulation of Cardiac Conduction and Arrhythmias by Ankyrin/Spectrin-Based Macromolecular Complexes

2021 ◽  
Vol 8 (5) ◽  
pp. 48
Author(s):  
Drew Nassal ◽  
Jane Yu ◽  
Dennison Min ◽  
Cemantha Lane ◽  
Rebecca Shaheen ◽  
...  
Keyword(s):  
Ion Channels ◽  
Cardiac Disease ◽  
Conduction System ◽  
Cytoskeletal Proteins ◽  
Cardiac Conduction ◽  
Proper Function ◽  
Cardiac Conduction System ◽  
Loss Of Function ◽  
Macromolecular Complexes ◽  
Conduction Disturbances

The cardiac conduction system is an extended network of excitable tissue tasked with generation and propagation of electrical impulses to signal coordinated contraction of the heart. The fidelity of this system depends on the proper spatio-temporal regulation of ion channels in myocytes throughout the conduction system. Importantly, inherited or acquired defects in a wide class of ion channels has been linked to dysfunction at various stages of the conduction system resulting in life-threatening cardiac arrhythmia. There is growing appreciation of the role that adapter and cytoskeletal proteins play in organizing ion channel macromolecular complexes critical for proper function of the cardiac conduction system. In particular, members of the ankyrin and spectrin families have emerged as important nodes for normal expression and regulation of ion channels in myocytes throughout the conduction system. Human variants impacting ankyrin/spectrin function give rise to a broad constellation of cardiac arrhythmias. Furthermore, chronic neurohumoral and biomechanical stress promotes ankyrin/spectrin loss of function that likely contributes to conduction disturbances in the setting of acquired cardiac disease. Collectively, this review seeks to bring attention to the significance of these cytoskeletal players and emphasize the potential therapeutic role they represent in a myriad of cardiac disease states.

Public-Private Partnership for the Development of Space Sector in the United States and Great Britain

2022 ◽  
pp. 76-87
Author(s):  
V. P. Zavarukhin ◽  
N. D. Frolova ◽  
D. V. Baibulatova
Keyword(s):  
Great Britain ◽  
Space Exploration ◽  
The United States ◽  
Public Private Partnership ◽  
Direct Application ◽  
High Tech ◽  
Private Partnership ◽  
Advantages And Disadvantages ◽  
Space Industry ◽  
Space Activities

The article provides an analysis of modern trends in building public-private partnership (PPP), gives an overview of key studies devoted to this subject in general and PPPs in the field of space activities in particular. The authors analyze the practice of public-private partnerships in the U. S. and Great Britain on the examples of specific mechanisms, their key features, advantages and disadvantages that determine the possibility of their application in different areas of government-business cooperation in the field of space exploration. In order to find possible ways for direct application or adaptation of this experience in Russia for organizing space exploration PPPs the researchers concluded that the level of high-tech production in this country is insufficient and significant administrative barriers for attracting private sector into the space industry are still present.

scholarly journals Exploring R&D Influences on Financial Performance for Business Sustainability Considering Dual Profitability Objectives

2017 ◽  
Author(s):  
Kao-Yi Shen ◽  
Min-Ren Yan ◽  
Gwo-Hshiung Tzeng
Keyword(s):  
Financial Performance ◽  
Soft Computing ◽  
Evaluation Model ◽  
Hybrid Approach ◽  
Multiple Criteria Decision Making ◽  
High Tech ◽  
Computing Technique ◽  
Business Sustainability ◽  
Soft Computing Technique ◽  
Dual Objectives

The influence and importance of research and development (R&D) for business sustainability have gained increasing interests, especially in the high-tech sector. However, the efforts of R&D might cause complex and mixed impacts on the financial results considering the associated expenses. Thus, this study aims to examine how R&D efforts may influence business to improve its financial performance considering the dual objectives: the gross and the net profitability. This research integrated a rough-set-based soft computing technique and multiple criteria decision-making (MCDM) methods to explore this complex and yet valuable issue. A group of public listed companies from Taiwan, all in the semiconductor sector, was analyzed as a case study. Initially, more than 30 variables were considered, and the adopted soft computing technique retrieved 14 core attributes—for the dual profitability objectives—to form the evaluation model. The importance of R&D for pursuing superior financial prospects is confirmed, and the empirical case demonstrates how to guide an individual company to plan for improvements to achieve its long-term sustainability by this hybrid approach.

Congenital atrioventricular block: clinical presentation, clinical evaluation, and management

ESC CardioMed ◽  
2018 ◽  
pp. 1966-1968
Author(s):  
Drago Fabrizio ◽  
Battipaglia Irma
Keyword(s):  
Heart Disease ◽  
Atrioventricular Block ◽  
Pacemaker Implantation ◽  
Cardiac Conduction ◽  
Ventricular Rate ◽  
Postnatal Life ◽  
Av Block ◽  
Cardiac Stimulation ◽  
Immune Mediated ◽  
Congenital Atrioventricular Block

Congenital atrioventricular block (CAVB) is a cardiac conduction disorder that is diagnosed in utero, at birth, or within the first month of life. When it is diagnosed between the first month and the 18th year of life, it is defined as childhood atrioventricular (AV) block. CAVB may occur in association with concomitant congenital heart disease, or be isolated, in a structurally normal heart (e.g. immune-mediated, inherited, or idiopathic CAVB). The majority of isolated CAVB is an immune-mediated AV block, due to transplacental passage of maternal autoantibodies, damaging the fetal cardiac conduction system. Only in a third of infants with immune-mediated CAVB is a well-defined autoimmune disease known in the mother. During fetal life, fetal echocardiography still represents the gold standard for the diagnosis of CAVB. Two major negative prognostic markers are low ventricular rate and the appearance of foetal hydrops. As regards prognosis, a risk for heart failure, syncope, and sudden death is present both during fetal and postnatal life. Dilated cardiomyopathy represents another complication in CAVB history, with different possible aetiologies (right ventricular permanent pacing, reactivation of autoimmune myocarditis). The indications for pacemaker implantation in patients with CAVB are similar to those for acquired heart disease, with some special technical considerations due to young age (epicardial versus endocardial systems, pacing site, etc.). As a future perspective, leadless cardiac stimulation in children with CAVB may represent a definitive solution and an answer to many questions.

Interplay between P2Y1, P2Y12, and P2X1 receptors in the activation of megakaryocyte cation influx currents by ADP: evidence that the primary megakaryocyte represents a fully functional model of platelet P2 receptor signaling

Blood ◽  
2005 ◽  
Vol 106 (5) ◽  
pp. 1644-1651 ◽  
Author(s):  
Gwen Tolhurst ◽  
Catherine Vial ◽  
Catherine Léon ◽  
Christian Gachet ◽  
Richard J. Evans ◽  
...  
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Functional Model ◽  
Receptor Potential ◽  
Adenosine Diphosphate ◽  
Receptor Signaling ◽  
P2 Receptor ◽  
Direct Stimulation ◽  
Initial Current ◽  
P2x1 Receptor

Abstract The difficulty of conducting electrophysiologic recordings from the platelet has restricted investigations into the role of ion channels in thrombosis and hemostasis. We now demonstrate that the well-established synergy between P2Y1 and P2Y12 receptors during adenosine diphosphate (ADP)–dependent activation of the platelet αIIbβ3 integrin also exists in murine marrow megakaryocytes, further supporting the progenitor cell as a bona fide model of platelet P2 receptor signaling. In patch clamp recordings, ADP (30 μM) stimulated a transient inward current at –70 mV, which was carried by Na+ and Ca2+ and was amplified by phenylarsine oxide, a potentiator of certain transient receptor potential (TRP) ion channels by phosphatidylinositol 4,5-bisphosphate depletion. This initial current decayed to a sustained phase, upon which repetitive transient inward cation currents with pre-dominantly P2X1-like kinetics were super-imposed. Abolishing P2X1-receptor activity prevented most of the repetitive currents, consistent with their activation by secreted adenosine triphosphate (ATP). Recordings in P2Y1-receptor–deficient megakaryocytes demonstrated an essential requirement of this receptor for activation of all ADP-evoked inward currents. However, P2Y12 receptors, through the activation of PI3-kinase, played a synergistic role in both P2Y1 and P2X1-receptor–dependent currents. Thus, direct stimulation of P2Y1 and P2Y12 receptors, together with autocrine P2X1 activation, is responsible for the activation of nonselective cation currents by the platelet agonistADP.

scholarly journals Cardiac Emerinopathy

2020 ◽  
Vol 13 (10) ◽  
Author(s):  
Taisuke Ishikawa ◽  
Hiroyuki Mishima ◽  
Julien Barc ◽  
Masanori P. Takahashi ◽  
Keiichi Hirono ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Left Ventricular ◽  
Cardiac Conduction ◽  
Conduction Disturbance ◽  
Ventricular Noncompaction ◽  
Increased Risk ◽  
Genes Encoding ◽  
History Of ◽  
Cardiac Conduction Defect ◽  
Female Carriers

Background: Mutations in the nuclear envelope genes encoding LMNA and EMD are responsible for Emery-Dreifuss muscular dystrophy. However, LMNA mutations often manifest dilated cardiomyopathy with conduction disturbance without obvious skeletal myopathic complications. On the contrary, the phenotypic spectrums of EMD mutations are less clear. Our aims were to determine the prevalence of nonsyndromic forms of emerinopathy, which may underlie genetically undefined isolated cardiac conduction disturbance, and the etiology of thromboembolic complications associated with EMD mutations. Methods: Targeted exon sequencing was performed in 87 probands with familial sick sinus syndrome (n=36) and a progressive cardiac conduction defect (n=51). Results: We identified 3 X-linked recessive EMD mutations (start-loss, splicing, missense) in families with cardiac conduction disease. All 3 probands shared a common clinical phenotype of progressive atrial arrhythmias that ultimately resulted in atrial standstill associated with left ventricular noncompaction (LVNC), but they lacked early contractures and progressive muscle wasting and weakness characteristic of Emery-Dreifuss muscular dystrophy. Because the association of LVNC with EMD has never been reported, we further genetically screened 102 LVNC patients and found a frameshift EMD mutation in a boy with progressive atrial standstill and LVNC without complications of muscular dystrophy. All 6 male EMD mutation carriers of 4 families underwent pacemaker or defibrillator implantation, whereas 2 female carriers were asymptomatic. Notably, a strong family history of stroke observed in these families was probably due to the increased risk of thromboembolism attributable to both atrial standstill and LVNC. Conclusions: Cardiac emerinopathy is a novel nonsyndromic X-linked progressive atrial standstill associated with LVNC and increased risk of thromboembolism.

Meeting Technology: From Low-Tech to High-Tech

1998 ◽  
Vol 61 (2) ◽  
pp. 80-87 ◽  
Author(s):  
Mary Munter
Keyword(s):  
High Tech ◽  
Face To Face ◽  
Advantages And Disadvantages ◽  
Electronic Meetings ◽  
E Mail

This article describes a series of low-tech and high-tech options for use in meeting management and summarizes the advantages and disadvantages of each. These options include (1) face-to-face meetings, with choices of flipcharts, non-electronic boards, electronic boards, handouts, still projectors, and multimedia projectors; and (2) groupware meetings, with choices of audio- and videoteleconferencing, e-mail meetings, and electronic meetings.

scholarly journals Imaging and Documenting Gammarideans

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Carolin Haug ◽  
Gerd Mayer ◽  
Verena Kutschera ◽  
Dieter Waloszek ◽  
Andreas Maas ◽  
...  
Keyword(s):  
Laser Scanning ◽  
Focused Ion Beam ◽  
Ion Beam ◽  
Polarized Light ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
High Tech ◽  
Advantages And Disadvantages ◽  
Computed Microtomography ◽  
Document Structures

We give an overview of available techniques for imaging and documenting applied to gammarideans and discuss their advantages and disadvantages. Although recent techniques, such as confocal laser scanning microscopy (cLSM), focused ion beam scanning electron microscopy (FIB SEM), or computed microtomography (μCT), provide new possibilities to detect and document structures, these high-tech devices are expensive, and access to them is often limited. Alternatively, there are many possibilities to enhance the capabilities of established techniques such as macrophotography and light microscopy. We discuss improvements of the illumination with polarized light and the possibilities of utilizing the autofluorescence of animals such as the gammarideans. In addition, we present software-based enhancing tools such as image fusion and image stitching.

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