scholarly journals NTPase/helicase of Flaviviridae: inhibitors and inhibition of the enzyme.

2002 ◽  
Vol 49 (3) ◽  
pp. 597-614 ◽  
Author(s):  
Peter Borowski ◽  
Andreas Niebuhr ◽  
Herbert Schmitz ◽  
Ramachandra S Hosmane ◽  
Maria Bretner ◽  
...  
Keyword(s):  
Antiviral Agents ◽  
Large Family ◽  
Enzymatic Activities ◽  
Structural Protein ◽  
Knock Out ◽  
Antiviral Therapies ◽  
Wide Range ◽  
Development And Differentiation ◽  
Transcription And Replication

RNA nucleoside triphosphatases (NTPase)/helicases represent a large family of proteins that are ubiquitously distributed over a wide range of organisms. The enzymes play essential role in cell development and differentiation, and some of them are involved in transcription and replication of viral single-stranded RNA genomes. The enzymatic activities of a NTPase/helicase were also detected in the carboxyl-terminal non-structural protein 3 (NS3) of members of the Flaviviridae family. The crucial role of the enzyme for the virus life cycle was demonstrated in knock out experiments and by using NTPase/helicase specific inhibitors. This makes the enzyme an attractive target for development of Flaviviridae-specific antiviral therapies. This review will summarize our knowledge about the function and structure of the enzyme, update the spectrum of inhibitors of the enzymatic activities of the NTPase/helicase and describe the different mechanisms by which the compounds act. Some of the compounds reviewed herein could show potential utility as antiviral agents against Flaviviridae viruses.

scholarly journals Is Autism a Member of a Family of Diseases Resulting from Genetic/Cultural Mismatches? Implications for Treatment and Prevention

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Staci D. Bilbo ◽  
John P. Jones ◽  
William Parker
Keyword(s):  
Large Family ◽  
Modern Medicine ◽  
Entire Family ◽  
Postindustrial Society ◽  
Typical Member ◽  
Treatment And Prevention ◽  
Wide Range ◽  
High Prevalence ◽  
Lines Of Evidence

Several lines of evidence support the view that autism is a typical member of a large family of immune-related, noninfectious, chronic diseases associated with postindustrial society. This family of diseases includes a wide range of inflammatory, allergic, and autoimmune diseases and results from consequences of genetic/culture mismatches which profoundly destabilize the immune system. Principle among these consequences is depletion of important components, particularly helminths, from the ecosystem of the human body, the human biome. Autism shares a wide range of features in common with this family of diseases, including the contribution of genetics/epigenetics, the identification of disease-inducing triggers, the apparent role of immunity in pathogenesis, high prevalence, complex etiologies and manifestations, and potentially some aspects of epidemiology. Fortunately, using available resources and technology, modern medicine has the potential to effectively reconstitute the human biome, thus treating or even avoiding altogether the consequences of genetic/cultural mismatches which underpin this entire family of disease. Thus, if indeed autism is an epidemic of postindustrial society associated with immune hypersensitivity, we can expect that the disease is readily preventable.

scholarly journals The Role of TRP Channels in Migraine

2013 ◽  
Vol 6 (1) ◽  
pp. 37-49 ◽  
Author(s):  
Gerry Stephen Oxford ◽  
Joyce Harts Hurley
Keyword(s):  
Trp Channels ◽  
Large Family ◽  
Trigeminovascular System ◽  
Peripheral Tissues ◽  
Wide Range ◽  
The Family ◽  
The Status ◽  
Physical Stimuli ◽  
Pain Transduction

TRP channels are members of a large family of non-selective cation channels. The family which numbers over 30 is classified into 6 groups based on amino acid sequence homology. TRP channels are distributed in many peripheral tissues as well as central and peripheral nervous system. These channels are important in sensing a wide range of chemical and physical stimuli. Several TRP channels, including TRPV1 and TRPA1 are important in pain transduction pathways. This review will focus on the function of TRP channels in the trigeminovascular system and other anatomical regions which are relevant to migraine. We will discuss the possible role of TRP channels in migraine, including the potential role of TRPV1 in the hypersensitivity and allodynia frequently observed in migraine patients. We will review the status of TRP channel drugs in migraine therapeutics. We will also discuss the possible roles of TRP channels in triggering migraine attacks, a process which is not well-understood.

scholarly journals SIRT5 is a proviral factor that interacts with SARS-CoV-2 Nsp14 protein

2022 ◽  
Author(s):  
Marius Walter ◽  
Irene P Chen ◽  
Albert Vallejo-Gracia ◽  
Ik-Jung Kim ◽  
Olga Bielska ◽  
...  
Keyword(s):  
Viral Replication ◽  
Catalytic Domain ◽  
Therapeutic Interventions ◽  
Stable Complex ◽  
Structural Protein ◽  
Knock Out ◽  
Protein Interactome ◽  
Lysine Residues ◽  
Dependent Protein

SARS-CoV-2 non-structural protein Nsp14 is a highly conserved enzyme necessary for viral replication. Nsp14 forms a stable complex with non-structural protein Nsp10 and exhibits exoribonuclease and N7-methyltransferase activities. Protein-interactome studies identified human sirtuin 5 (SIRT5) as a putative binding partner of Nsp14. SIRT5 is an NAD-dependent protein deacylase critical for cellular metabolism that removes succinyl and malonyl groups from lysine residues. Here we investigated the nature of this interaction and the role of SIRT5 during SARS-CoV-2 infection. We showed that SIRT5 stably interacts with Nsp14, but not with Nsp10, suggesting that SIRT5 and Nsp10 are parts of separate complexes. We found that SIRT5 catalytic domain is necessary for the interaction with Nsp14, but that Nsp14 does not appear to be directly deacylated by SIRT5. Furthermore, knock-out of SIRT5 or treatment with specific SIRT5 inhibitors reduced SARS-CoV-2 viral levels in cell-culture experiments. SIRT5 knock-out cells expressed higher basal levels of innate immunity markers and mounted a stronger antiviral response. Our results indicate that SIRT5 is a proviral factor necessary for efficient viral replication, which opens novel avenues for therapeutic interventions.

scholarly journals Antiviral Properties of Flavonoids and Delivery Strategies

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2534 ◽  
Author(s):  
Paolino Ninfali ◽  
Antonella Antonelli ◽  
Mauro Magnani ◽  
Emanuele Salvatore Scarpa
Keyword(s):  
Molecular Mechanisms ◽  
Viral Infections ◽  
Biological Effects ◽  
Antiviral Agents ◽  
Synthetic Drugs ◽  
Antiviral Therapies ◽  
Antiviral Effects ◽  
Wide Range ◽  
Antiviral Activities ◽  
Delivery Strategies

This review summarizes the latest advancements in phytochemicals as functional antiviral agents. We focused on flavonoids, like apigenin, vitexin, quercetin, rutin and naringenin, which have shown a wide range of biological effects including antiviral activities. The molecular mechanisms of their antiviral effects mainly consist in the inhibition of viral neuraminidase, proteases and DNA/RNA polymerases, as well as in the modification of various viral proteins. Mixtures of different flavonoids or combination of flavonoids with antiviral synthetic drugs provide an enhancement of their antiviral effects. Recent strategies in drug delivery significantly contribute to overcoming the low bioavailability of flavonoids. Frequent viral infections worldwide have led to the need for new effective antiviral agents, which can be identified among the various phytochemicals. In this light, screening the antiviral activities of a cocktail of flavonoids would be advantageous in order to prevent viral infections and improve current antiviral therapies.

scholarly journals Identification of Cellular Factors Required for SARS-CoV-2 Replication

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3159
Author(s):  
Aleksandra Synowiec ◽  
Malwina Jedrysik ◽  
Wojciech Branicki ◽  
Adrianna Klajmon ◽  
Jing Lei ◽  
...  
Keyword(s):  
Complex Analysis ◽  
Multiorgan Failure ◽  
Severe Disease ◽  
Antiviral Agents ◽  
Interaction Network ◽  
Knock Out ◽  
Interesting Insight ◽  
A Genome ◽  
Wide Range ◽  
Species Specific

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the recently emerged virus responsible for the COVID-19 pandemic. Clinical presentation can range from asymptomatic disease and mild respiratory tract infection to severe disease with lung injury, multiorgan failure, and death. SARS-CoV-2 is the third animal coronavirus to emerge in humans in the 21st century, and coronaviruses appear to possess a unique ability to cross borders between species and infect a wide range of organisms. This is somewhat surprising as, except for the requirement of host cell receptors, cell–pathogen interactions are usually species-specific. Insights into these host–virus interactions will provide a deeper understanding of the process of SARS-CoV-2 infection and provide a means for the design and development of antiviral agents. In this study, we describe a complex analysis of SARS-CoV-2 infection using a genome-wide CRISPR-Cas9 knock-out system in HeLa cells overexpressing entry receptor angiotensin-converting enzyme 2 (ACE2). This platform allows for the identification of factors required for viral replication. This study was designed to include a high number of replicates (48 replicates; 16 biological repeats with 3 technical replicates each) to prevent data instability, remove sources of bias, and allow multifactorial bioinformatic analyses in order to study the resulting interaction network. The results obtained provide an interesting insight into the replication mechanisms of SARS-CoV-2.

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.

Short Films from a Small Nation

2018 ◽  
Author(s):  
C. Claire Thomson
Keyword(s):  
Public Information ◽  
Industrial Process ◽  
Actor Network Theory ◽  
Documentary Films ◽  
Wide Range ◽  
Short Films ◽  
Post War ◽  
The 1960S ◽  
Art And Architecture

The first book-length study in English of a national corpus of state-sponsored informational film, this book traces how Danish shorts on topics including social welfare, industry, art and architecture were commissioned, funded, produced and reviewed from the inter-war period to the 1960s. For three decades, state-sponsored short filmmaking educated Danish citizens, promoted Denmark to the world, and shaped the careers of renowned directors like Carl Th. Dreyer. Examining the life cycle of a representative selection of films, and discussing their preservation and mediation in the digital age, this book presents a detailed case study of how informational cinema is shaped by, and indeed shapes, its cultural, political and technological contexts.The book combines close textual analysis of a broad range of films with detailed accounts of their commissioning, production, distribution and reception in Denmark and abroad, drawing on Actor-Network Theory to emphasise the role of a wide range of entities in these processes. It considers a broad range of genres and sub-genres, including industrial process films, public information films, art films, the city symphony, the essay film, and many more. It also maps international networks of informational and documentary films in the post-war period, and explores the role of informational film in Danish cultural and political history.

Quantitative and Qualitative Methods of Studying the Processes of Socialization of a Modern Teenager

2020 ◽  
pp. 102-109
Author(s):  
Svetlana Alekseevna Raschetina ◽  
Keyword(s):  
Research Methods ◽  
Interpersonal Relations ◽  
Internet Communication ◽  
Socialization Process ◽  
Wide Range ◽  
The Family ◽  
Modern Family ◽  
Making Friends ◽  
Main Support

Relevance and problem statement. Modern unstable society is characterized by narrowing the boundaries of controlled socialization and expanding the boundaries of spontaneous socialization of a teenager based on his immersion in the question arises about the importance of the family in the process of socialization of a teenager in the conditions of expanding the space of socialization. There is a need to study the role of the family in this process, to search, develop and test research methods that allow us to reveal the phenomenon of socialization from the side of its value characteristics. The purpose and methodology of the study: to identify the possibilities of a systematic and anthropological methodology for studying the role of the family in the process of socialization of adolescents in modern conditions, testing research methods: photo research on the topic “Ego – I” (author of the German sociologist H. Abels), profile update reflexive processes (by S. A. Raschetina). Materials and results of the study. The study showed that for all the problems that exist in the family of the perestroika era and in the modern family, it acts for a teenager as a value and the first (main) support in the processes of socialization. The positions well known in psychology about the importance of interpersonal relations in adolescence for the formation of attitudes towards oneself as the basis of socialization are confirmed. Today, the frontiers of making friends have expanded enormously on the basis of Internet communication. The types of activities of interest to a teenager (traditional and new ones related to digitalization) are the third pillar of socialization. Conclusion. The “Ego – I” method of photo research has a wide range of possibilities for quantitative and qualitative analysis of the socialization process to identify the value Pillars of this process.

Victorian Culture and Classical Antiquity

2011 ◽  
Author(s):  
Simon Goldhill
Keyword(s):  
Nineteenth Century ◽  
Roman Empire ◽  
Classical Antiquity ◽  
Victorian Culture ◽  
Wide Range ◽  
Victorian Art ◽  
Victorian Science ◽  
Role Of Religion ◽  
Nineteenth Century Novels

How did the Victorians engage with the ancient world? This book is an exploration of how ancient Greece and Rome influenced Victorian culture. Through Victorian art, opera, and novels, the book examines how sexuality and desire, the politics of culture, and the role of religion in society were considered and debated through the Victorian obsession with antiquity. Looking at Victorian art, it demonstrates how desire and sexuality, particularly anxieties about male desire, were represented and communicated through classical imagery. Probing into operas of the period, the book addresses ideas of citizenship, nationalism, and cultural politics. And through fiction—specifically nineteenth-century novels about the Roman Empire—it discusses religion and the fierce battles over the church as Christianity began to lose dominance over the progressive stance of Victorian science and investigation. Rediscovering some great forgotten works and reframing some more familiar ones, the book offers extraordinary insights into how the Victorian sense of antiquity and our sense of the Victorians came into being. With a wide range of examples and stories, it demonstrates how interest in the classical past shaped nineteenth-century self-expression, giving antiquity a unique place in Victorian culture.

Sign in / Sign up

Export Citation Format

Share Document