scholarly journals Evidence of Adaptive Evolution in Wolbachia-Regulated Gene DNMT2 and Its Role in the Dipteran Immune Response and Pathogen Blocking

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1464
Author(s):  
Tamanash Bhattacharya ◽  
Danny W. Rice ◽  
John M. Crawford ◽  
Richard W. Hardy ◽  
Irene L. G. Newton
Keyword(s):  
Immune Response ◽  
Positive Selection ◽  
Mosquito Species ◽  
Fruit Fly ◽  
Host Protein ◽  
Wide Range ◽  
Regulation Function ◽  
Specific Factors ◽  
And Function

Eukaryotic nucleic acid methyltransferase (MTase) proteins are essential mediators of epigenetic and epitranscriptomic regulation. DNMT2 belongs to a large, conserved family of DNA MTases found in many organisms, including holometabolous insects such as fruit flies and mosquitoes, where it is the lone MTase. Interestingly, despite its nomenclature, DNMT2 is not a DNA MTase, but instead targets and methylates RNA species. A growing body of literature suggests that DNMT2 mediates the host immune response against a wide range of pathogens, including RNA viruses. Curiously, although DNMT2 is antiviral in Drosophila, its expression promotes virus replication in mosquito species. We, therefore, sought to understand the divergent regulation, function, and evolution of these orthologs. We describe the role of the Drosophila-specific host protein IPOD in regulating the expression and function of fruit fly DNMT2. Heterologous expression of these orthologs suggests that DNMT2′s role as an antiviral is host-dependent, indicating a requirement for additional host-specific factors. Finally, we identify and describe potential evidence of positive selection at different times throughout DNMT2 evolution within dipteran insects. We identify specific codons within each ortholog that are under positive selection and find that they are restricted to four distinct protein domains, which likely influence substrate binding, target recognition, and adaptation of unique intermolecular interactions. Collectively, our findings highlight the evolution of DNMT2 in Dipteran insects and point to structural, regulatory, and functional differences between mosquito and fruit fly homologs.

scholarly journals Adaptive evolution in DNMT2 supports its role in the dipteran immune response

2020 ◽  
Author(s):  
Tamanash Bhattacharya ◽  
Danny W. Rice ◽  
Richard W. Hardy ◽  
Irene L.G. Newton
Keyword(s):  
Immune Response ◽  
Positive Selection ◽  
Adaptive Evolution ◽  
Fruit Fly ◽  
Fruit Flies ◽  
Host Protein ◽  
Specific Host ◽  
Wide Range ◽  
Specific Factors

AbstractEukaryotic nucleic acid methyltransferase (MTase) proteins are essential mediators of epigenetic and epitranscriptomic regulation. DNMT2 belongs to a large, conserved family of DNA MTases found in many organisms, including holometabolous insects like fruit flies and mosquitoes, where it is the lone MTase. Interestingly, despite its nomenclature, DNMT2 is not a DNA MTase, but instead targets and methylates RNA species. A growing body of literature suggest DNMT2 mediates the host immune response against a wide range of pathogens, including RNA viruses. Evidence of adaptive evolution, in the form of positive selection, can often be found in genes that are engaged in conflict with pathogens like viruses. Here we identify and describe evidence of positive selection that has occurred at different times over the course of DNMT2 evolution within dipteran insects. We identify specific codons within each ortholog that are under positive selection, and find they are restricted to four distinct domains of the protein and likely influence substrate binding, target recognition, and adaptation of unique intermolecular interactions. Additionally, we describe the role of the Drosophila-specific host protein IPOD, in regulating the expression and/or function of fruit fly DNMT2. Finally, heterologous expression of these orthologs suggest that DNMT2’s role as an antiviral is host dependent, indicating a requirement for additional host-specific factors. Collectively, our findings highlight the adaptive evolution of DNMT2 in Dipteran insects, underscoring its role as an important, albeit non-canonical, regulator of host-pathogen interactions in mosquitoes and fruit flies.

scholarly journals Thioester-Containing Protein-4 Regulates the Drosophila Immune Signaling and Function against the Pathogen Photorhabdus

2016 ◽  
Vol 9 (1) ◽  
pp. 83-93 ◽  
Author(s):  
Upasana Shokal ◽  
Ioannis Eleftherianos
Keyword(s):  
Immune Response ◽  
Photorhabdus Luminescens ◽  
Human Pathogen ◽  
Loss Of Function ◽  
Phenoloxidase Activity ◽  
Microbial Infections ◽  
Immune Pathways ◽  
And Function ◽  
Important Progress

Despite important progress in identifying the molecules that participate in the immune response of Drosophila melanogaster to microbial infections, the involvement of thioester-containing proteins (TEPs) in the antibacterial immunity of the fly is not fully clarified. Previous studies mostly focused on identifying the function of TEP2, TEP3 and TEP6 molecules in the D. melanogaster immune system. Here, we investigated the role of TEP4 in the regulation and function of D. melanogaster host defense against 2 virulent pathogens from the genus Photorhabdus, i.e. the insect pathogenic bacterium Photorhabdus luminescens and the emerging human pathogen P. asymbiotica. We demonstrate that Tep4 is strongly upregulated in adult flies following the injection of Photorhabdus bacteria. We also show that Tep4 loss-of-function mutants are resistant to P. luminescens but not to P. asymbiotica infection. In addition, we find that inactivation of Tep4 results in the upregulation of the Toll and Imd immune pathways, and the downregulation of the Jak/Stat and Jnk pathways upon Photorhabdus infection. We document that loss of Tep4 promotes melanization and phenoloxidase activity in the mutant flies infected with Photorhabdus. Together, these findings generate novel insights into the immune role of TEP4 as a regulator and effector of the D. melanogaster antibacterial immune response.

A Review on Role of Macro and Micro Banking Environment on Non-Performing Assets Management

2019 ◽  
pp. 281-294
Author(s):  
Biswajit Prasad Chhatoi ◽  
Sharada Prasad Sahoo
Keyword(s):  
Critical Role ◽  
Banking System ◽  
Financial Assets ◽  
Policy Changes ◽  
Public And Private ◽  
Private Banks ◽  
Specific Factors ◽  
And Function ◽  
Asset Creation

In a self-resilient economy, banking system assumes importance in imparting momentum to economic growth and prosperity through mobilization of financial assets. Performance of banks, irrespective of their nature and function, is germane to their asset creation and maintenance capacity. In a neo-liberal regime, radical policy changes have crept into loan mechanism, thereby subjecting the banks to efficiently recover the loans, which is a vital asset for any banking firm. In this context, the authors through intensive review of literature identified micro and macro banking factors responsible for productive NPA management. The macro banking factors refer to the economic environment whereas the micro banking factors refer to the bank and branch-specific factors. The authors identified the critical role of organizational structure, involvement of employees, and organizational efficiency in driving prudent NPA management. The authors have found that the efficiency in managing NPAs differ in public and private banks, which is attributed to involvement of employees.

scholarly journals Cerebrovascular Changes and Neurodegeneration Related to Hyperlipidemia: Characteristics of the Human ApoB-100 Transgenic Mice

2020 ◽  
Vol 26 (13) ◽  
pp. 1486-1494 ◽  
Author(s):  
Melinda E. Tóth ◽  
Brigitta Dukay ◽  
Zsófia Hoyk ◽  
Miklós Sántha
Keyword(s):  
Transgenic Mouse ◽  
Serum Lipid ◽  
Lipoprotein Metabolism ◽  
Transgenic Mouse Models ◽  
Wild Type ◽  
Lipid Levels ◽  
Cerebrovascular Lesions ◽  
Wide Range ◽  
And Function

Serum lipid levels are closely related to the structure and function of blood vessels. Chronic hyperlipidemia may lead to damage in both the cardio- and the cerebrovascular systems. Vascular dysfunctions, including impairments of the blood-brain barrier, are known to be associated with neurodegenerative diseases. A growing number of evidence suggests that cardiovascular risk factors, such as hyperlipidemia, may increase the likelihood of developing dementia. Due to differences in lipoprotein metabolism, wild-type mice are protected against dietinduced hypercholesterolemia, and their serum lipid profile is different from that observed in humans. Therefore, several transgenic mouse models have been established to study the role of different apolipoproteins and their receptors in lipid metabolism, as well as the complications related to pathological lipoprotein levels. This minireview focused on a transgenic mouse model overexpressing an apolipoprotein, the human ApoB-100. We discussed literature data and current advancements on the understanding of ApoB-100 induced cardio- and cerebrovascular lesions in order to demonstrate the involvement of this type of apolipoprotein in a wide range of pathologies, and a link between hyperlipidemia and neurodegeneration.

scholarly journals Role of Exosomes in Islet Transplantation

2021 ◽  
Vol 12 ◽  
Author(s):  
Jordan Mattke ◽  
Srividya Vasu ◽  
Carly M. Darden ◽  
Kenjiro Kumano ◽  
Michael C. Lawrence ◽  
...  
Keyword(s):  
Islet Transplantation ◽  
Graft Function ◽  
Pancreatic Islet Transplantation ◽  
Complex Molecules ◽  
Wide Range ◽  
And Function ◽  
Antigen Presenting

Exosomes are known for their ability to transport nucleic acid, lipid, and protein molecules, which allows for communication between cells and tissues. The cargo of the exosomes can have a variety of effects on a wide range of targets to mediate biological function. Pancreatic islet transplantation is a minimally invasive cell replacement therapy to prevent or reverse diabetes mellitus and is currently performed in patients with uncontrolled type 1 diabetes or chronic pancreatitis. Exosomes have become a focus in the field of islet transplantation for the study of diagnostic markers of islet cell viability and function. A growing list of miRNAs identified from exosomes collected during the process of isolating islets can be used as diagnostic biomarkers of islet stress and damage, leading to a better understanding of critical steps of the isolation procedure that can be improved to increase islet yield and quality. Exosomes have also been implicated as a possible contributor to islet graft rejection following transplantation, as they carry donor major histocompatibility complex molecules, which are then processed by recipient antigen-presenting cells and sensed by the recipient immune cells. Exosomes may find their way into the therapeutic realm of islet transplantation, as exosomes isolated from mesenchymal stem cells have shown promising results in early studies that have seen increased viability and functionality of isolated and grafted islets in vitro as well as in vivo. With the study of exosomes still in its infancy, continued research on the role of exosomes in islet transplantation will be paramount to understanding beta cell regeneration and improving long-term graft function.

scholarly journals Using technology to connect generations: Some considerations of form and function

Comunicar ◽  
2015 ◽  
Vol 23 (45) ◽  
pp. 95-104 ◽  
Author(s):  
Mariano Sánchez-Martínez ◽  
Matthew Kaplan ◽  
Leah Bradley
Keyword(s):  
Intergenerational Relationships ◽  
Relationship Formation ◽  
Positive Potential ◽  
Technology Learning ◽  
Form And Function ◽  
Wide Range ◽  
Generational Groups ◽  
And Function ◽  
Los Grupos

Nowadays, as ageing increases in Western societies it has become more evident that multiple generations are ageing concurrently at any given time in history. Therefore, ageing must be approached as a multi-generational phenomenon, not just as a question of elders. In this context, situations that engender increased interactions between generations are garnering more attention. There is a growing emphasis on expanding the role of technology in intergenerational programmes, within the field of intergenerational studies. Consequently, this paper is focused on education and learning processes within intergenerational programmes with a strong technology component. Information from a total of 46 intergenerational programmes from 11 countries has been gathered through a survey. Level of impact, status of generational groups, and centrality of technology have been appraised for all programmes in the sample. Technology learning-teaching constitute the main area of intended impact of these programmes. However, the surveyed programmes employ as well a wide range of strategies to facilitate intergenerational communication, cooperation and relationship formation between generations involved. Interest of programmes examined does not just consist of teaching the use technology but of experimenting with technology in different forms and functions and exploring the positive potential for enhancing intergenerational relationships Actualmente, conforme el envejecimiento en las sociedades occidentales aumenta, resulta más evidente que en cualquier momento histórico dado hay varias generaciones envejeciendo simultáneamente. Por tanto, el envejecimiento debe ser estudiado como fenómeno multi-generacional y no solo como un asunto de personas mayores. En este contexto, están suscitando más atención las situaciones que implican más interacciones intergeneracionales. Dentro del campo intergeneracional está aumentando el interés en torno a las posibilidades de expandir el papel de la tecnología en los programas intergeneracionales. En consecuencia, este artículo se centra en los procesos de educación y aprendizaje acaecidos dentro de programas intergeneracionales con un fuerte componente tecnológico. Mediante un sondeo se recogió información sobre un total de 46 de este tipo de programas de 11 países. Todos se han evaluado en la muestra según su nivel de impacto, el estatus de los grupos generacionales y la centralidad de la tecnología. La enseñanza-aprendizaje de la tecnología constituye la principal área de impacto buscada por estos programas, que, no obstante, también utilizan una amplia variedad de estrategias para facilitar la comunicación, la cooperación y la formación de relaciones intergeneracionales entre las generaciones implicadas. El interés de los programas analizados no solo consiste en enseñar a utilizar la tecnología sino en experimentar diferentes formas y funciones con ella, así como en explorar el potencial positivo de la tecnología para mejorar las relaciones intergeneracionales

scholarly journals Email Consultations Between Patients and Doctors in Primary Care: Content Analysis

10.2196/18218 ◽  
2020 ◽  
Vol 22 (11) ◽  
pp. e18218
Author(s):  
Helen Atherton ◽  
Anne-Marie Boylan ◽  
Abi Eccles ◽  
Joanna Fleming ◽  
Clare R Goyder ◽  
...  
Keyword(s):  
Primary Care ◽  
General Practice ◽  
Content Analysis ◽  
Communication Technologies ◽  
Face To Face ◽  
The United Kingdom ◽  
Wide Range ◽  
The Face ◽  
And Function

Background Increasingly, consultations in health care settings are conducted remotely using a range of communication technologies. Email allows for 2-way text-based communication, occurring asynchronously. Studies have explored the content and nature of email consultations to understand the use, structure, and function of email consultations. Most previous content analyses of email consultations in primary care settings have been conducted in North America, and these have shown that concerns and assumptions about how email consultations work have not been realized. There has not been a UK-based content analysis of email consultations. Objective This study aims to explore and delineate the content of consultations conducted via email in English general practice by conducting a content analysis of email consultations between general practitioners (GPs) and patients. Methods We conducted a content analysis of anonymized email consultations between GPs and patients in 2 general practices in the United Kingdom. We examined the descriptive elements of the correspondence to ascertain when the emails were sent, the number of emails in an email consultation, and the nature of the content. We used a normative approach to analyze the content of the email consultations to explore the use and function of email consultation. Results We obtained 100 email consultations from 85 patients, which totaled 262 individual emails. Most email users were older than 40 years, and over half of the users were male. The email consultations were mostly short and completed in a few days. Emails were mostly sent and received during the day. The emails were mostly clinical in content rather than administrative and covered a wide range of clinical presentations. There were 3 key themes to the use and function of the email consultations: the role of the GP and email consultation, the transactional nature of an email consultation, and the operationalization of an email consultation. Conclusions Most cases where emails are used to have a consultation with a patient in general practice have a shorter consultation, are clinical in nature, and are resolved quickly. GPs approach email consultations using key elements similar to that of the face-to-face consultation; however, using email consultations has the potential to alter the role of the GP, leading them to engage in more administrative tasks than usual. Email consultations were not a replacement for face-to-face consultations.

scholarly journals The Multifarious Role of 14-3-3 Family of Proteins in Viral Replication

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 436 ◽  
Author(s):  
Kavitha Ganesan Nathan ◽  
Sunil K. Lal
Keyword(s):  
Protein Interactions ◽  
Viral Infections ◽  
Pharmaceutical Research ◽  
Host Protein ◽  
Dna Viruses ◽  
Wide Range ◽  
Host Virus Interactions ◽  
Virus Interactions ◽  
Rna And Dna

The 14-3-3 proteins are a family of ubiquitous and exclusively eukaryotic proteins with an astoundingly significant number of binding partners. Their binding alters the activity, stability, localization, and phosphorylation state of a target protein. The association of 14-3-3 proteins with the regulation of a wide range of general and specific signaling pathways suggests their crucial role in health and disease. Recent studies have linked 14-3-3 to several RNA and DNA viruses that may contribute to the pathogenesis and progression of infections. Therefore, comprehensive knowledge of host–virus interactions is vital for understanding the viral life cycle and developing effective therapeutic strategies. Moreover, pharmaceutical research is already moving towards targeting host proteins in the control of virus pathogenesis. As such, targeting the right host protein to interrupt host–virus interactions could be an effective therapeutic strategy. In this review, we generated a 14-3-3 protein interactions roadmap in viruses, using the freely available Virusmentha network, an online virus–virus or virus–host interaction tool. Furthermore, we summarize the role of the 14-3-3 family in RNA and DNA viruses. The participation of 14-3-3 in viral infections underlines its significance as a key regulator for the expression of host and viral proteins.

scholarly journals Zinc, Vitamin D and Vitamin C: Perspectives for COVID-19 With a Focus on Physical Tissue Barrier Integrity

2020 ◽  
Vol 7 ◽  
Author(s):  
José João Name ◽  
Ana Carolina Remondi Souza ◽  
Andrea Rodrigues Vasconcelos ◽  
Pietra Sacramento Prado ◽  
Carolina Parga Martins Pereira
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Viral Infections ◽  
Adequate Intake ◽  
High Demand ◽  
Comprehensive Overview ◽  
Disease Prognosis ◽  
Mucous Membranes ◽  
And Function

Some nutrients play key roles in maintaining the integrity and function of the immune system, presenting synergistic actions in steps determinant for the immune response. Among these elements, zinc and vitamins C and D stand out for having immunomodulatory functions and for playing roles in preserving physical tissue barriers. Considering the COVID-19 pandemic, nutrients that can optimize the immune system to prevent or lower the risk of severe progression and prognosis of this viral infection become relevant. Thus, the present review aims to provide a comprehensive overview of the roles of zinc and vitamins C and D in the immune response to viral infections, focusing on the synergistic action of these nutrients in the maintenance of physical tissue barriers, such as the skin and mucous membranes. The evidence found in the literature shows that deficiency of one or more of these three elements compromises the immune response, making an individual more vulnerable to viral infections and to a worse disease prognosis. Thus, during the COVID-19 pandemic, the adequate intake of zinc and vitamins C and D may represent a promising pharmacological tool due to the high demand for these nutrients in the case of contact with the virus and onset of the inflammatory process. Ongoing clinical trials will help to clarify the role of these nutrients for COVID-19 management.

scholarly journals Lipophilicity of Bacteriochlorin-Based Photosensitizers as a Determinant for PDT Optimization through the Modulation of the Inflammatory Mediators

2019 ◽  
Vol 9 (1) ◽  
pp. 8 ◽  
Author(s):  
Barbara Pucelik ◽  
Luis G. Arnaut ◽  
Janusz M. Dąbrowski
Keyword(s):  
Immune Response ◽  
Molecular Mechanisms ◽  
Near Infrared ◽  
Antitumor Immune Response ◽  
Infrared Light ◽  
Gm Csf ◽  
Hydrophobic Compound ◽  
Tnf Α ◽  
Wide Range

Photodynamic therapy (PDT) augments the host antitumor immune response, but the role of the PDT effect on the tumor microenvironment in dependence on the type of photosensitizer and/or therapeutic protocols has not been clearly elucidated. We employed three bacteriochlorins (F2BOH, F2BMet and Cl2BHep) of different polarity that absorb near-infrared light (NIR) and generated a large amount of reactive oxygen species (ROS) to compare the PDT efficacy after various drug-to-light intervals: 15 min. (V-PDT), 3h (E-PDT) and 72h (C-PDT). We also performed the analysis of the molecular mechanisms of PDT crucial for the generation of the long-lasting antitumor immune response. PDT-induced damage affected the integrity of the host tissue and developed acute (protocol-dependent) local inflammation, which in turn led to the infiltration of neutrophils and macrophages. In order to further confirm this hypothesis, a number of proteins in the plasma of PDT-treated mice were identified. Among a wide range of cytokines (IL-6, IL-10, IL-13, IL-15, TNF-α, GM-CSF), chemokines (KC, MCP-1, MIP1α, MIP1β, MIP2) and growth factors (VEGF) released after PDT, an important role was assigned to IL-6. PDT protocols optimized for studied bacteriochlorins led to a significant increase in the survival rate of BALB/c mice bearing CT26 tumors, but each photosensitizer (PS) was more or less potent, depending on the applied DLI (15 min, 3 h or 72 h). Hydrophilic (F2BOH) and amphiphilic (F2BMet) PSs were equally effective in V-PDT (>80 cure rate). F2BMet was the most efficient in E-PDT (DLI = 3h), leading to a cure of 65 % of the animals. Finally, the most powerful PS in the C-PDT (DLI = 72 h) regimen turned out to be the most hydrophobic compound (Cl2BHep), allowing 100 % of treated animals to be cured at a light dose of only 45 J/cm2.

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