scholarly journals Silencing of the Baculovirus Op-iap3 Gene by RNA Interference Reveals that It Is Required for Prevention of Apoptosis during Orgyia pseudotsugata M Nucleopolyhedrovirus Infection of Ld652Y Cells

2003 ◽  
Vol 77 (8) ◽  
pp. 4481-4488 ◽  
Author(s):  
John C. Means ◽  
Israel Muro ◽  
Rollie J. Clem
Keyword(s):  
Rna Interference ◽  
Double Stranded Rna ◽  
Orgyia Pseudotsugata ◽  
Baculovirus Gene ◽  
Wide Range ◽  
Infected Cells ◽  
Rnai Technique ◽  
Almost All ◽  
First Time

ABSTRACT The Op-iap3 gene from the baculovirus Orgyia pseudotsugata M nucleopolyhedrovirus (OpMNPV) inhibits apoptosis induced by a mutant of Autographa californica MNPV (AcMNPV) that lacks the antiapoptotic gene p35, as well as apoptosis induced by a wide range of other stimuli in both mammalian and insect cells. However, the role of Op-iap3 during OpMNPV infection has not been previously examined. To determine the function of the Op-IAP3 protein during OpMNPV infection, we used RNA interference (RNAi) to silence Op-iap3 expression during OpMNPV infection of Ld652Y cells. Infected cells treated with Op-iap3 double-stranded RNA (dsRNA) did not accumulate detectable Op-iap3 mRNA, confirming that the Op-iap3 gene was effectively silenced. Op-IAP3 protein was found to be a component of the budded virion; however, in OpMNPV-infected cells treated with Op-iap3 dsRNA, the Op-IAP3 protein that was introduced by the inoculum virus decreased to almost undetectable levels by 12 h after dsRNA addition. Apoptosis was observed in infected cells treated with Op-iap3 dsRNA beginning at 12 h, and by 48 h, almost all of the cells had undergone apoptosis. These results show for the first time that Op-IAP3 is necessary to prevent apoptosis during OpMNPV infection. In addition, our results demonstrate that the RNAi technique can be an effective tool for studying baculovirus gene function.

scholarly journals Viroids as a Tool to Study RNA-Directed DNA Methylation in Plants

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1187
Author(s):  
Michael Wassenegger ◽  
Athanasios Dalakouras
Keyword(s):  
Dna Methylation ◽  
Rna Interference ◽  
Gene Silencing ◽  
Plant Cells ◽  
Transcriptional Gene Silencing ◽  
Rnai Machinery ◽  
Double Stranded Rna ◽  
Post Transcriptional Gene Silencing ◽  
Cumulative Amount

Viroids are plant pathogenic, circular, non-coding, single-stranded RNAs (ssRNAs). Members of the Pospiviroidae family replicate in the nucleus of plant cells through double-stranded RNA (dsRNA) intermediates, thus triggering the host’s RNA interference (RNAi) machinery. In plants, the two RNAi pillars are Post-Transcriptional Gene Silencing (PTGS) and RNA-directed DNA Methylation (RdDM), and the latter has the potential to trigger Transcriptional Gene Silencing (TGS). Over the last three decades, the employment of viroid-based systems has immensely contributed to our understanding of both of these RNAi facets. In this review, we highlight the role of Pospiviroidae in the discovery of RdDM, expound the gradual elucidation through the years of the diverse array of RdDM’s mechanistic details and propose a revised RdDM model based on the cumulative amount of evidence from viroid and non-viroid systems.

scholarly journals Functional analysis of the putative antiapoptotic genes, p49 and iap4, of Spodoptera litura nucleopolyhedrovirus with RNAi

2008 ◽  
Vol 89 (8) ◽  
pp. 1873-1880 ◽  
Author(s):  
Qian Yu ◽  
Tiehao Lin ◽  
Guozhong Feng ◽  
Kai Yang ◽  
Yi Pang
Keyword(s):  
Spodoptera Litura ◽  
Virus Production ◽  
Host Cells ◽  
Homology Search ◽  
Pcr Analysis ◽  
Viability Analysis ◽  
Infected Cells ◽  
Budded Virus ◽  
Almost All

A homology search of a public database revealed that Spodoptera litura nucleopolyhedrovirus (SpltNPV) possesses two putative, antiapoptotic genes, p49 and inhibitor of apoptosis 4 (iap4), but their function has not been investigated in its native host cells. In the present study, we used RNA interference (RNAi) to silence the expression of Splt-iap4 and Splt-p49, independently or together, to determine their roles during the SpltNPV life cycle. RT-PCR analysis and Western blot analysis showed the target gene expression had been knocked out in the SpltNPV-infected SpLi-221 cells after treatment with Splt-p49 or Splt-iap4 double-stranded RNA (dsRNA), respectively, confirming that the two genes were effectively silenced. In SpltNPV-infected cells treated with Splt-p49 dsRNA, apoptosis was observed beginning at 14 h, and almost all cells had undergone apoptosis by 48 h. In contrast, budded virus production and polyhedra formation progressed normally in infected cells treated with Splt-iap4 dsRNA. Cell viability analysis showed that Splt-IAP4 had no synergistic effect on the inhibition of apoptosis of SpLi-221 cells induced by SpltNPV infection. Interestingly, after Splt-iap4 dsRNA treatment, cells did not congregate like those infected with SpltNPV in the early infection phase, implying an unknown role of baculovirus iap4. Our results determine that Splt-p49 is necessary to prevent apoptosis; however, Splt-iap4 has no antiapoptotic function during SpltNPV infection.

scholarly journals A functional spleen contributes to afucosylated IgG in humans

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Iwona Wojcik ◽  
David E. Schmidt ◽  
Lisa A. de Neef ◽  
Minke A. E. Rab ◽  
Bob Meek ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Infections ◽  
Immune Cell ◽  
Lymphoid Organ ◽  
Immune Effector ◽  
Adaptive Immune ◽  
Wide Range ◽  
Humoral Responses ◽  
First Time

AbstractAs a lymphoid organ, the spleen hosts a wide range of immune cell populations, which not only remove blood-borne antigens, but also generate and regulate antigen-specific immune responses. In particular, the splenic microenvironment has been demonstrated to play a prominent role in adaptive immune responses to enveloped viral infections and alloantigens. During both types of immunizations, antigen-specific immunoglobulins G (IgGs) have been characterized by the reduced amount of fucose present on N-linked glycans of the fragment crystallizable (Fc) region. These glycans are essential for mediating the induction of immune effector functions. Therefore, we hypothesized that a spleen may modulate humoral responses and serve as a preferential site for afucosylated IgG responses, which potentially play a role in immune thrombocytopenia (ITP) pathogenesis. To determine the role of the spleen in IgG-Fc glycosylation, we performed IgG subclass-specific liquid chromatography–mass spectrometry (LC–MS) analysis of Fc glycosylation in a large cohort of individuals splenectomized due to trauma, due to ITP, or spherocytosis. IgG-Fc fucosylation was consistently increased after splenectomy, while no effects for IgG-Fc galactosylation and sialylation were observed. An increase in IgG1- and IgG2/3-Fc fucosylation level upon splenectomy has been reported here for the first time, suggesting that immune responses occurring in the spleen may be particularly prone to generate afucosylated IgG responses. Surprisingly, the level of total IgG-Fc fucosylation was decreased in ITP patients compared to healthy controls. Overall, our results suggest a yet unrecognized role of the spleen in either the induction or maintenance of afucosylated IgG responses by B cells.

scholarly journals FcγRIIIa receptor polymorphism influences NK cell mediated ADCC activity against HIV

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Sneha Pramod Talathi ◽  
Nawaj Najir Shaikh ◽  
Sudhanshu Shekhar Pandey ◽  
Vandana Ashish Saxena ◽  
Megha Sunil Mamulwar ◽  
...  
Keyword(s):  
Cell Activation ◽  
Nk Cell ◽  
Killer Cell ◽  
Adcc Activity ◽  
Efficient Treatment ◽  
Activation Assay ◽  
Dependent Cell ◽  
Infected Cells ◽  
First Time

Abstract Background HIV-specific Antibody Dependent Cell Cytotoxicity (ADCC) has shown to be important in HIV control and resistance. The ADCC is mediated primarily by natural killer cell activated through the binding of FcγRIIIa receptor to the Fc portion of antibody bound to the antigen expressed on the infected cells. However, no data is available on the influence of the polymorphism in FcγRIIIa receptor on HIV-specific ADCC response. Methods The Sanger’s method of sequencing was used to sequence the exon of FcγRIIIa receptor while the ADCC activity was determined using NK cell activation assay. The polymorphism in FcγRIIIa receptor was assessed in HIV-infected Indian individuals with or without HIV-specific ADCC antibodies and its influence on the magnitude of HIV-specific ADCC responses was analyzed. Results Two polymorphisms: V176F (rs396991) and Y158H (rs396716) were observed. The Y158H polymorphism is reported for the first time in Indian population. Both, V176F (V/V genotype) (p = 0.004) and Y158H (Y/H genotype) (p = 0.032) were found to be significantly associated with higher magnitude of HIV-specific ADCC response. Conclusion The study underscores the role of polymorphism in the FcγRIIIa receptor on HIV-specific ADCC response and suggests that the screening of the individuals for FcγRIIIa-V176F and Y158H polymorphisms could be useful for prediction of efficient treatment in monoclonal antibody-based therapies aimed at ADCC in HIV infection.

scholarly journals Lassa Virus, but Not Highly Pathogenic New World Arenaviruses, Restricts Immunostimulatory Double-Stranded RNA Accumulation during Infection

2020 ◽  
Vol 94 (9) ◽  
Author(s):  
Elizabeth J. Mateer ◽  
Junki Maruyama ◽  
Galen E. Card ◽  
Slobodan Paessler ◽  
Cheng Huang
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Lassa Virus ◽  
Innate Immune Responses ◽  
Highly Pathogenic ◽  
Double Stranded Rna ◽  
L Protein ◽  
Biochemical Assays ◽  
Infected Cells ◽  
First Time

ABSTRACT The arenaviruses Lassa virus (LASV), Junín virus (JUNV), and Machupo virus (MACV) can cause severe and fatal diseases in humans. Although these pathogens are closely related, the host immune responses to these virus infections differ remarkably, with direct implications for viral pathogenesis. LASV infection is immunosuppressive, with a very low-level interferon response. In contrast, JUNV and MACV infections stimulate a robust interferon (IFN) response in a retinoic acid-inducible gene I (RIG-I)-dependent manner and readily activate protein kinase R (PKR), a known host double-stranded RNA (dsRNA) sensor. In response to infection with RNA viruses, host nonself RNA sensors recognize virus-derived dsRNA as danger signals and initiate innate immune responses. Arenavirus nucleoproteins (NPs) contain a highly conserved exoribonuclease (ExoN) motif, through which LASV NP has been shown to degrade virus-derived immunostimulatory dsRNA in biochemical assays. In this study, we for the first time present evidence that LASV restricts dsRNA accumulation during infection. Although JUNV and MACV NPs also have the ExoN motif, dsRNA readily accumulated in infected cells and often colocalized with dsRNA sensors. Moreover, LASV coinfection diminished the accumulation of dsRNA and the IFN response in JUNV-infected cells. The disruption of LASV NP ExoN with a mutation led to dsRNA accumulation and impaired LASV replication in minigenome systems. Importantly, both LASV NP and RNA polymerase L protein were required to diminish the accumulation of dsRNA and the IFN response in JUNV infection. For the first time, we discovered a collaboration between LASV NP ExoN and L protein in limiting dsRNA accumulation. Our new findings provide mechanistic insights into the differential host innate immune responses to highly pathogenic arenavirus infections. IMPORTANCE Arenavirus NPs contain a highly conserved DEDDh ExoN motif, through which LASV NP degrades virus-derived, immunostimulatory dsRNA in biochemical assays to eliminate the danger signal and inhibit the innate immune response. Nevertheless, the function of NP ExoN in arenavirus infection remains to be defined. In this study, we discovered that LASV potently restricts dsRNA accumulation during infection and minigenome replication. In contrast, although the NPs of JUNV and MACV also harbor the ExoN motif, dsRNA readily formed during JUNV and MACV infections, accompanied by IFN and PKR responses. Interestingly, LASV NP alone was not sufficient to limit dsRNA accumulation. Instead, both LASV NP and L protein were required to restrict immunostimulatory dsRNA accumulation. Our findings provide novel and important insights into the mechanism for the distinct innate immune response to these highly pathogenic arenaviruses and open new directions for future studies.

scholarly journals THE METHODOLOGY OF ANALYSIS OF J. JOYCE'S NOVEL "ULISSES" (EMPHASES OF DARIA VIKONSKA)

2021 ◽  
pp. 67-75
Author(s):  
M. Moklytsia
Keyword(s):  
Research Work ◽  
The Novel ◽  
Literary Forms ◽  
Literary Process ◽  
Self Knowledge ◽  
Ethical Norms ◽  
Almost All ◽  
First Time ◽  
School Curricula

The relevance of the study is due to the need to include the novel "Ulysses" by J. Joyce in university and, if possible, school curricula in foreign literature, as well as the need for its interpretation, despite the excessive complexity of the text and difficulty of perception. It is also important to return the legacy of D. Vikonska, a writer, critic, art critic and literary critic, to modern Ukrainian culture. Research methodology: a model of analysis of the modernist novel "Ulysses", created on the basis of the research work of D. Vikonska “James Joyce. The secret of his artistic face” (1934). Scientific novelty: for the first time the analysis of the novel "Ulysses" is carried out with the broad involvement of the half-forgotten studio of D. Vikonska, which has not lost its relevance, clearly articulates the modernist nature of the work, including surreal style. The purpose of the study: to draw attention to the outstanding figure of D. Vikonska as the founder of Ukrainian Joyce studies, to include her in the modern literary process, to show with her help the significant role of Joyce's novel "Ulysses". Conclusions. The answer to the question why Joyce's novel Ulysses is considered a landmark work of modernism should be concise but convincing, based on macro- and microanalysis of the text. First of all, it is a unique example of the author's self-expression, extreme subjectivism (the whimsy of Joyce's nature), transformed into universalism. No one is as subjective as Joyce is, no one is as universal as he is. Such can only be a conscious modernist who has passed the difficult path of search outside, in the world of culture, and inside, looking into the irrational depths of his own psyche. This is the most rational, intellectual and at the same time irrational, or visionary, according to K.G. Jung, type of creativity. Second: this is the boldest (revolutionary, in the words of Vikonska) challenge to tradition (or Cultural Canon, according to K.G. Jung), which manifested itself in the ironic parody of almost all known literary forms and narrative means, many moral and ethical norms. Third: it is a brilliant example of the author's style, a variant of surrealism, which grows out of naturalism and turns into neomythologism. Joyce's style is characterized by the following features: associative metaphorical writing, author's dictionary, which includes numerous innovations, narrative reception of the flow of consciousness; use of dreams, delusions, other boundary conditions; a bizarre intertwining of past and present, when dead and living characters are equal in meaning; consistent reflection of the external in the internal and vice versa; a labyrinth of human wanderings in search of pleasures, meaning, cognition and self-knowledge. Joyce modeled the next stage in the development of culture – the transition from modernism to postmodernism, from an ironic re-reading of tradition to playing with it.

scholarly journals Foresight as a tool of public administration in the field of science, technology and innovation

2021 ◽  
Vol 8 (1) ◽  
pp. 90-97
Author(s):  
T. Kvasha ◽  
◽  
L. Musina ◽  
Keyword(s):  
New Technologies ◽  
National Level ◽  
Research And Innovation ◽  
Science Technology ◽  
Wide Range ◽  
Smart Specialization ◽  
High Level ◽  
First Time ◽  
Science Technology And Innovation

Given the growing role of technological foresight as a tool for reconciling visions, goals and ways of STI development in an era of rapid technological change and global challenges, the approach to foresight research to select priorities for science and innovation in Ukraine for 2022–2026 has been improved. It takes into account a wide range of national targets for achieving SDGs by 2030. The developed Methodological recommendations provided a thorough analysis of more than 3,000 potentially acceptable technological and innovative proposals. The approach to setting STI priorities is new for Ukraine and involves a consistent process of selecting the top 30 most acceptable proposals in each of the seven thematic areas through five stages of discussions and evaluations. The result was the formation of a database of technology passports and developments on the experts’ proposals, their selection by practitioners, ranking, evaluation in terms of the potential of Ukrainian science and relevance in terms of world science and new technologies using international databases. They are the basis for decisions by the Expert Councils and the High-Level Working Group on key thematic areas and the preparation of a relevant draft government decision. Despite the conditions of quarantine, for the first time more than 2,500 experts from science, business, state and public organizations took part in the discussions, which is the basis for impartial and public decision-making. To strengthen the role of foresight as a tool for public planning and management in the field of STI, it is proposed to develop a STI roadmap as part of a research and innovation strategy for smart specialization (RIS 3) at the national level.

scholarly journals Study of Oil in the North of Russia by the Geological Committee at the End of the 19th Century – the Beginning of the 20th Century

2021 ◽  
Vol 937 (4) ◽  
pp. 042082
Author(s):  
T P Filippova
Keyword(s):  
Field Studies ◽  
The Arctic ◽  
Russian Science ◽  
The North ◽  
New Information ◽  
Wide Range ◽  
Northern Territories ◽  
The 19Th Century ◽  
First Time

Abstract The article draws attention to the study of the historical experience of Russian science in the development of the Arctic and northern territories of Russia. Based on a wide range of archival and published sources, the role of the Geological Committee in the scientific study of the Ukhta oil-bearing region is analyzed. The chronological framework of the study covers the period of the organization’s activity from 1882 to 1929. The field studies carried out by the Geological Committee which started during this period in the Ukhta region are considered in detail. As a result of this activity, this territory was comprehensively studied for the first time, including a detailed geological survey, the search for oil deposits, and an assessment of its industrial potential. It has been determined that as a result of the surveys of the Geological Committee, new information about the features of the geological and orographic structure of the region was obtained and the oil-bearing potential was proved. It has been concluded that the research of the scientists of the committee laid a fundamental basis for the study of the Ukhta oil-bearing region and predetermined its further development history and great significance for the state.

scholarly journals Host-microbiome coevolution promotes cooperation in a rock-paper-scissor dynamic

2019 ◽  
Author(s):  
Ohad Lewin-Epstein ◽  
Lilach Hadany
Keyword(s):  
Computational Modeling ◽  
Potential Role ◽  
Evolution Of Cooperation ◽  
Host Behavior ◽  
Wide Range ◽  
Forms Of Life ◽  
New Perspective ◽  
Almost All ◽  
And Behavior

AbstractCooperation is a fundamental behavior observed in all forms of life. The evolution of cooperation has been widely studied, but almost all theories focused on the cooperating individual and its genes. We suggest a different approach, taking into account the microbes carried by the interacting individuals. Accumulating evidence reveal that microbes can affect their host wellbeing and behavior, yet hosts can evolve mechanisms to resist the manipulations of their microbes. We thus propose that coevolution of microbes with their hosts may favor microbes that induce their host to cooperate. Using computational modeling, we show that microbe-induced cooperation can evolve and be maintained in a wide range of conditions, including when facing hosts’ resistance to the microbial effect. We find that host-microbe coevolution leads the population to a rock-paper-scissors dynamic, that enables maintenance of cooperation in a polymorphic state. This theory may help explain occurrences of cooperation in a wide variety of organisms, including in cases that are difficult to explain by current theories. In addition, this study provides a new perspective on the coevolution of hosts and their microbiome, emphasizing the potential role of microbes in shaping their host behavior.

scholarly journals Ivermectin the Promising Drug to Stave off the COVID-19 Crisis: A Review

2021 ◽  
Vol 7 (2) ◽  
pp. 95-98
Author(s):  
Zakia Jahan ◽  
Masudul Hassan
Keyword(s):  
Infectious Diseases ◽  
Specific Treatment ◽  
In Vitro Study ◽  
Antiviral Effect ◽  
Viral Particles ◽  
The World ◽  
Infected Cells ◽  
Almost All ◽  
First Time

The Coronavirus disease 2019 (COVID-19) outbreak, forcing us to face unprecedented moments in the world. The huge devastating impact of the world due to the covid-19 attack causes the brink of no return. However, there is no proven and specific treatment for Covid -19. Very few medications have received Emergency Use of Authorization. A recent in vitro study was the first time to find out and to assess the antiviral effect of Ivermectin on COVID-19. The study showed that Ivermectin was active against COVID- 19-infected cells, was able to kill effectively almost all viral particles within 48 h. In these moments of crisis, FDA-approved ivermectin is a ray of hope. Bangladesh Journal of Infectious Diseases 2020;7(2):95-98

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