scholarly journals Pathogenesis of the initial stages of severe COVID-19

2021 ◽  
Vol 12 (2) ◽  
pp. 83-102
Author(s):  
A S. Golota ◽  
Tatyana A. Kamilova ◽  
Olga V. Shneider ◽  
Dmitry A. Vologzhanin ◽  
Sergey G. Sherbak
Keyword(s):  
Reproductive Organs ◽  
Body Fluids ◽  
Effective Strategies ◽  
Organ Systems ◽  
Heart Blood ◽  
Viral Components ◽  
Innate Antiviral Immunity ◽  
Different Levels ◽  
Shed Light

Since SARS-CoV-2 first appeared in humans, the scientific community has tried to gather as much information as possible in order to find effective strategies for the containment and treatment this pandemic coronavirus. We reviewed the current published literature on SARS-CoV-2 with an emphasis on the distribution of SARS-CoV-2 in tissues and body fluids, as well as data on the expression of its input receptors on the cell surface. COVID-19 affects many organ systems in many ways. These varied manifestations are associated with viral tropism and immune responses of the infected person, but the exact mechanisms are not yet fully understood. We emphasize the broad organotropism of SARS-CoV-2, as many studies have identified viral components (RNA, proteins) in many organs, including immune cells, pharynx, trachea, lungs, blood, heart, blood vessels, intestines, brain, kidneys, and male reproductive organs. Viral components are present in various body fluids, such as mucus, saliva, urine, cerebrospinal fluid, semen and breast milk. The main SARS-CoV-2 receptor, ACE2, is expressed at different levels in many tissues throughout the human body, but its expression levels do not always correspond to the detection of SARS-CoV-2, indicating a complex interaction between the virus and humans. We also highlight the role of the renin-angiotensin aldosterone system and its inhibitors in the context of COVID-19. In addition, SARS-CoV-2 has various strategies that are widely used in various tissues to evade innate antiviral immunity. Targeting immune evasion mediators of the virus can block its replication in COVID-19 patients. Together, these data shed light on the current understanding of the pathogenesis of SARS-CoV-2 and lay the groundwork for better diagnosis and treatment of patients with COVID-19.

scholarly journals Nucleic acid binding by SAMHD1 contributes to the antiretroviral activity and is enhanced by the GpsN modification

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Corey H. Yu ◽  
Akash Bhattacharya ◽  
Mirjana Persaud ◽  
Alexander B. Taylor ◽  
Zhonghua Wang ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Binding Sites ◽  
Nucleic Acid Binding ◽  
Allosteric Sites ◽  
Protein Dephosphorylation ◽  
Allosteric Binding Sites ◽  
Innate Antiviral Immunity ◽  
Shed Light ◽  
Antiretroviral Activity

AbstractSAMHD1 impedes infection of myeloid cells and resting T lymphocytes by retroviruses, and the enzymatic activity of the protein—dephosphorylation of deoxynucleotide triphosphates (dNTPs)—implicates enzymatic dNTP depletion in innate antiviral immunity. Here we show that the allosteric binding sites of the enzyme are plastic and can accommodate oligonucleotides in place of the allosteric activators, GTP and dNTP. SAMHD1 displays a preference for oligonucleotides containing phosphorothioate bonds in the Rp configuration located 3’ to G nucleotides (GpsN), the modification pattern that occurs in a mechanism of antiviral defense in prokaryotes. In the presence of GTP and dNTPs, binding of GpsN-containing oligonucleotides promotes formation of a distinct tetramer with mixed occupancy of the allosteric sites. Mutations that impair formation of the mixed-occupancy complex abolish the antiretroviral activity of SAMHD1, but not its ability to deplete dNTPs. The findings link nucleic acid binding to the antiretroviral activity of SAMHD1, shed light on the immunomodulatory effects of synthetic phosphorothioated oligonucleotides and raise questions about the role of nucleic acid phosphorothioation in human innate immunity.

scholarly journals Immunoinflammatory, Thrombohaemostatic, and Cardiovascular Mechanisms in COVID-19

2020 ◽  
Vol 120 (12) ◽  
pp. 1629-1641
Author(s):  
Selin Gencer ◽  
Michael Lacy ◽  
Dorothee Atzler ◽  
Emiel P. C. van der Vorst ◽  
Yvonne Döring ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Viral Entry ◽  
Treatment Options ◽  
Microvascular Dysfunction ◽  
Organ Systems ◽  
Number Of Patients ◽  
History Of ◽  
Potential Impact ◽  
Shed Light

AbstractThe global coronavirus disease 2019 (COVID-19) pandemic has deranged the recent history of humankind, afflicting more than 27 million individuals to date. While the majority of COVID-19 patients recuperate, a considerable number of patients develop severe complications. Bilateral pneumonia constitutes the hallmark of severe COVID-19 disease but an involvement of other organ systems, namely the cardiovascular system, kidneys, liver, and central nervous system, occurs in at least half of the fatal COVID-19 cases. Besides respiratory failure requiring ventilation, patients with severe COVID-19 often display manifestations of systemic inflammation and thrombosis as well as diffuse microvascular injury observed postmortem. In this review, we survey the mechanisms that may explain how viral entry and activation of endothelial cells by severe acute respiratory syndrome coronavirus 2 can give rise to a series of events including systemic inflammation, thrombosis, and microvascular dysfunction. This pathophysiological scenario may be particularly harmful in patients with overt cardiovascular disease and may drive the fatal aspects of COVID-19. We further shed light on the role of the renin–angiotensin aldosterone system and its inhibitors in the context of COVID-19 and discuss the potential impact of antiviral and anti-inflammatory treatment options. Acknowledging the comorbidities and potential organ injuries throughout the course of severe COVID-19 is crucial in the clinical management of patients affecting treatment approaches and recovery rate.

scholarly journals Advances and challenges in skeletal muscle angiogenesis

2016 ◽  
Vol 310 (3) ◽  
pp. H326-H336 ◽  
Author(s):  
I. Mark Olfert ◽  
Oliver Baum ◽  
Ylva Hellsten ◽  
Stuart Egginton
Keyword(s):  
Skeletal Muscle ◽  
Capillary Density ◽  
Endocrine Function ◽  
Future Research ◽  
Physiological Regulation ◽  
Pathological Angiogenesis ◽  
Organ Systems ◽  
New Findings ◽  
Different Levels

The role of capillaries is to serve as the interface for delivery of oxygen and removal of metabolites to/from tissues. During the past decade there has been a proliferation of studies that have advanced our understanding of angiogenesis, demonstrating that tissue capillary supply is under strict control during health but poorly controlled in disease, resulting in either excessive capillary growth (pathological angiogenesis) or losses in capillarity (rarefaction). Given that skeletal muscle comprises nearly 40% of body mass in humans, skeletal muscle capillary density has a significant impact on metabolism, endocrine function, and locomotion and is tightly regulated at many different levels. Skeletal muscle is also high adaptable and thus one of the few organ systems that can be experimentally manipulated (e.g., by exercise) to study physiological regulation of angiogenesis. This review will focus on the methodological concerns that have arisen in determining skeletal muscle capillarity and highlight the concepts that are reshaping our understanding of the angio-adaptation process. We also summarize selected new findings (physical influences, molecular changes, and ultrastructural rearrangement of capillaries) that identify areas of future research with the greatest potential to expand our understanding of how angiogenesis is normally regulated, and that may also help to better understand conditions of uncontrolled (pathological) angiogenesis.

On Future Directions in Pathology

1982 ◽  
Vol 40 ◽  
pp. 274-277
Author(s):  
Benjamin F. Trump ◽  
Irene K. Berezesky ◽  
Raymond T. Jones
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Clinical Pathology ◽  
Future Directions ◽  
Diagnostic Pathology ◽  
The Past ◽  
Transmission Electron ◽  
Organ Systems ◽  
The Many

The role of electron microscopy and associated techniques is assured in diagnostic pathology. At the present time, most of the progress has been made on tissues examined by transmission electron microscopy (TEM) and correlated with light microscopy (LM) and by cytochemistry using both plastic and paraffin-embedded materials. As mentioned elsewhere in this symposium, this has revolutionized many fields of pathology including diagnostic, anatomic and clinical pathology. It began with the kidney; however, it has now been extended to most other organ systems and to tumor diagnosis in general. The results of the past few years tend to indicate the future directions and needs of this expanding field. Now, in addition to routine EM, pathologists have access to the many newly developed methods and instruments mentioned below which should aid considerably not only in diagnostic pathology but in investigative pathology as well.

The Role of Zinc in Thyroid Hormones Metabolism

2019 ◽  
Vol 89 (1-2) ◽  
pp. 80-88 ◽  
Author(s):  
Juliana Soares Severo ◽  
Jennifer Beatriz Silva Morais ◽  
Taynáh Emannuelle Coelho de Freitas ◽  
Ana Letícia Pereira Andrade ◽  
Mayara Monte Feitosa ◽  
...  
Keyword(s):  
Thyroid Hormones ◽  
Scientific Evidence ◽  
Thyroid Stimulating Hormone ◽  
Zinc Transporters ◽  
Serum Concentrations ◽  
Metabolic Adaptations ◽  
Serum T3 ◽  
Regulatory Effects ◽  
Shed Light

Abstract. Thyroid hormones play an important role in body homeostasis by facilitating metabolism of lipids and glucose, regulating metabolic adaptations, responding to changes in energy intake, and controlling thermogenesis. Proper metabolism and action of these hormones requires the participation of various nutrients. Among them is zinc, whose interaction with thyroid hormones is complex. It is known to regulate both the synthesis and mechanism of action of these hormones. In the present review, we aim to shed light on the regulatory effects of zinc on thyroid hormones. Scientific evidence shows that zinc plays a key role in the metabolism of thyroid hormones, specifically by regulating deiodinases enzymes activity, thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH) synthesis, as well as by modulating the structures of essential transcription factors involved in the synthesis of thyroid hormones. Serum concentrations of zinc also appear to influence the levels of serum T3, T4 and TSH. In addition, studies have shown that Zinc transporters (ZnTs) are present in the hypothalamus, pituitary and thyroid, but their functions remain unknown. Therefore, it is important to further investigate the roles of zinc in regulation of thyroid hormones metabolism, and their importance in the treatment of several diseases associated with thyroid gland dysfunction.

The Adult as Foe or Friend?: Childism in Guus Kuijer's Criticism and Fiction

2013 ◽  
Vol 6 (2) ◽  
pp. 205-217 ◽  
Author(s):  
Vanessa Joosen
Keyword(s):  
Children's Literature ◽  
Children’S Literature ◽  
Age Groups ◽  
Children's Books ◽  
Children’S Books ◽  
Memorial Award ◽  
Adult Reader ◽  
Shed Light ◽  
Selection Of

Compared to the attention that children's literature scholars have paid to the construction of childhood in children's literature and the role of adults as authors, mediators and readers of children's books, few researchers have made a systematic study of adults as characters in children's books. This article analyses the construction of adulthood in a selection of texts by the Dutch author and Astrid Lindgren Memorial Award winner Guus Kuijer and connects them with Elisabeth Young-Bruehl's recent concept of ‘childism’ – a form of prejudice targeted against children. Whereas Kuijer published a severe critique of adulthood in Het geminachte kind [The despised child] (1980), in his literary works he explores a variety of positions that adults can take towards children, with varying degrees of childist features. Such a systematic and comparative analysis of the way grown-ups are characterised in children's texts helps to shed light on a didactic potential that materialises in different adult subject positions. After all, not only literary and artistic aspects of children's literature may be aimed at the adult reader (as well as the child), but also the didactic aspect of children's books can cross over between different age groups.

Value-driven issues throughout the development of sociological theory

2020 ◽  
pp. 147-160
Author(s):  
Gulbarshyn Chepurko ◽  
Valerii Pylypenko
Keyword(s):  
Social Interactions ◽  
Social System ◽  
Sociological Theory ◽  
Social Scientists ◽  
Social Sphere ◽  
Technological Advances ◽  
The Social ◽  
The Individual ◽  
Different Levels

The paper examines and compares how the major sociological theories treat axiological issues. Value-driven topics are analysed in view of their relevance to society in times of crisis, when both societal life and the very structure of society undergo dramatic change. Nowadays, social scientists around the world are also witnessing such a change due to the emergence of alternative schools of sociological thought (non-classical, interpretive, postmodern, etc.) and, subsequently, the necessity to revise the paradigms that have been existed in sociology so far. Since the above-mentioned approaches are often used to address value-related issues, building a solid theoretical framework for these studies takes on considerable significance. Furthermore, the paradigm revision has been prompted by technological advances changing all areas of people’s lives, especially social interactions. The global human community, integral in nature, is being formed, and production of human values now matters more than production of things; hence the “expansion” of value-focused perspectives in contemporary sociology. The authors give special attention to collectivities which are higher-order units of the social system. These units are described as well-organised action systems where each individual performs his/her specific role. Just as the role of an individual is distinct from that of the collectivity (because the individual and the collectivity are different as units), so too a distinction is drawn between the value and the norm — because they represent different levels of social relationships. Values are the main connecting element between the society’s cultural system and the social sphere while norms, for the most part, belong to the social system. Values serve primarily to maintain the pattern according to which the society is functioning at a given time; norms are essential to social integration. Apart from being the means of regulating social processes and relationships, norms embody the “principles” that can be applied beyond a particular social system. The authors underline that it is important for Ukrainian sociology to keep abreast of the latest developments in the field of axiology and make good use of those ideas because this is a prerequisite for its successful integration into the global sociological community.

Tax evasion in the medical profession An Empirical Study in the General Tax Authority in Iraq

2019 ◽  
Vol 118 (11) ◽  
pp. 80-88
Author(s):  
Ramyar Rzgar Ahmed ◽  
Hawkar Qasim Birdawod ◽  
S. Rabiyathul Basariya
Keyword(s):  
Tax Evasion ◽  
Income Tax ◽  
Medical Profession ◽  
Great Influence ◽  
Tax Law ◽  
Degree Of Confidence ◽  
Medical Professions ◽  
Shed Light

The study dealt with tax evasion in the medical profession, where the problem was the existence of many cases of tax evasion, especially tax evasion in the income tax of medical professions. The aim of the study is to try to shed light on the phenomenon of tax evasion and the role of the tax authority in the development of controls and means that reduce the phenomenon of tax evasion. The most important results of the low level of tax awareness and lack of knowledge of the tax law and the unwillingness to read it and the sense of taxpayers unfairness of the tax all lead to an increase in cases of tax evasion and in suggested tightening control and follow-up on the offices of auditors, through the investigation and auditing The reports of certified accountants and the use of computers for this purpose in order to raise the degree of confidence in these reports and bring them closer to the required truth and coordination and cooperation with the Union of Accountants and Auditors and inform them about each case of violations of the auditors and accountants N because of its great influence in the rejection of the organization of the accounts and not to ratify fake accounts lead to show taxpayers accounts on a non-truth in order to tax evasion.

РЕГІОНАЛЬНИЙ МИТЕЦЬ В ІНОКУЛЬТУРНОМУ СЕРЕДОВИЩІ: ПРОБЛЕМА ФУНКЦІОНУВАННЯ

2020 ◽  
pp. 152-158
Author(s):  
Admink Admink ◽  
Сергій Виткалов ◽  
Валентина Вігула
Keyword(s):  
Local Government ◽  
Cultural Practices ◽  
Local Population ◽  
Government Reform ◽  
Different Levels

Розглядається організаційно-культурна діяльність одного з помітних у регіональному просторі Західного Полісся фотомитця – Олександра Купчинського, а саме виставковий її вектор, втілений в презентації артефактів світового фотомистецтва; видавничий, розглянутий у  контексті  друку  різноманітних  фотоальбомів  із  творів експонентів, організація творчих зустрічей художньої інтелігенції міста з питань обговорення актуальних питань культурного розвитку, заснування фотоклубу тощо. Доводиться, що втрата зв’язку з Батьківщиною, у якій би формі це не відбувалося, не дозволяє митцю творчо самореалізуватися повною мірою. The importance and problematic range of local government reform in the regions of the country and ways of its solution in the field of culture are analyzed. The most effective steps are proposed for management structures at different levels to change attitudes of both the management and the local population regarding different cultural practices. Emphasis is placed on the role of sectoral methodological services in the implementation of this reform. The experience of other countries in activating the local population in this process is emphasized. An attempt has been made to offer effective, in the authors' opinion, solutions to the reform. Emphasis is placed on the educational factor.

Impact of the Fontan Operation on Organ Systems

2019 ◽  
Vol 19 (3) ◽  
pp. 205-214
Author(s):  
Miriam Michel ◽  
Manuela Zlamy ◽  
Andreas Entenmann ◽  
Karin Pichler ◽  
Sabine Scholl-Bürgi ◽  
...  
Keyword(s):  
Systematic Study ◽  
Fontan Operation ◽  
Gastrointestinal System ◽  
Adjunct Treatment ◽  
Organ Systems ◽  
Fontan Surgery ◽  
Fontan Patients

: In patients having undergone the Fontan operation, besides the well discussed changes in the cardiac, pulmonary and gastrointestinal system, alterations of further organ systems including the hematologic, immunologic, endocrinological and metabolic are reported. As a medical adjunct to Fontan surgery, the systematic study of the central role of the liver as a metabolizing and synthesizing organ should allow for a better understanding of the pathomechanism underlying the typical problems in Fontan patients, and in this context, the profiling of endocrinological and metabolic patterns might offer a tool for the optimization of Fontan follow-up, targeted monitoring and specific adjunct treatment.

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