scholarly journals Assembly of infectious enteroviruses depends on multiple, conserved genomic RNA-coat protein contacts

2020 ◽  
Vol 16 (12) ◽  
pp. e1009146
Author(s):  
Rebecca Chandler-Bostock ◽  
Carlos P. Mata ◽  
Richard J. Bingham ◽  
Eric C. Dykeman ◽  
Bo Meng ◽  
...  

Picornaviruses are important viral pathogens, but despite extensive study, the assembly process of their infectious virions is still incompletely understood, preventing the development of anti-viral strategies targeting this essential part of the life cycle. We report the identification, via RNA SELEX and bioinformatics, of multiple RNA sites across the genome of a typical enterovirus, enterovirus-E (EV-E), that each have affinity for the cognate viral capsid protein (CP) capsomer. Many of these sites are evolutionarily conserved across known EV-E variants, suggesting they play essential functional roles. Cryo-electron microscopy was used to reconstruct the EV-E particle at ~2.2 Å resolution, revealing extensive density for the genomic RNA. Relaxing the imposed symmetry within the reconstructed particles reveals multiple RNA-CP contacts, a first for any picornavirus. Conservative mutagenesis of the individual RNA-contacting amino acid side chains in EV-E, many of which are conserved across the enterovirus family including poliovirus, is lethal but does not interfere with replication or translation. Anti-EV-E and anti-poliovirus aptamers share sequence similarities with sites distributed across the poliovirus genome. These data are consistent with the hypothesis that these RNA-CP contacts are RNA Packaging Signals (PSs) that play vital roles in assembly and suggest that the RNA PSs are evolutionarily conserved between pathogens within the family, augmenting the current protein-only assembly paradigm for this family of viruses.

2005 ◽  
Vol 79 (11) ◽  
pp. 7005-7013 ◽  
Author(s):  
Katrin Peters ◽  
Tatiana Wiktorowicz ◽  
Martin Heinkelein ◽  
Axel Rethwilm

ABSTRACT Foamy viruses (FVs) generate their Pol protein precursor molecule independently of the Gag protein from a spliced mRNA. This mode of expression raises the question of the mechanism of Pol protein incorporation into the viral particle (capsid). We previously showed that the packaging of (pre)genomic RNA is essential for Pol encapsidation (M. Heinkelein, C. Leurs, M. Rammling, K. Peters, H. Hanenberg, and A. Rethwilm, J. Virol. 76:10069-10073, 2002). Here, we demonstrate that distinct sequences in the RNA, which we termed Pol encapsidation sequences (PES), are required to incorporate Pol protein into the FV capsid. Two PES were found, which are contained in the previously identified cis-acting sequences necessary to transfer an FV vector. One PES is located in the U5 region of the 5′ long terminal repeat and one at the 3′ end of the pol gene region. Neither element has any significant effect on RNA packaging. However, deletion of either PES resulted in a significant reduction in Pol encapsidation. On the protein level, we show that only the Pol precursor, but not the individual reverse transcriptase (RT) and integrase (IN) subunits, is incorporated into FV particles. However, enzymatic activities of the protease (PR), RT, or IN are not required. Our results strengthen the view that in FVs, (pre)genomic RNA functions as a bridging molecule between Gag and Pol precursor proteins.


2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Jyoti Narayan Patra ◽  
Jayanta Mete

Values are like seeds that sprout, become saplings, grow into trees and spread their branches all around. To be able to think right, to feel the right kind of emotions and to act in the desirable manner are the prime phases of personality development. Building up of values system starts with the individual, moves on to the family and community, reorienting systems, structures and institutions, spreading throughout the land and ultimately embracing the planet as a whole. The culture of inclusivity is particularly relevant and important in the context of our society, nation and making education a right for all children.


2020 ◽  
Vol 1 (10(79)) ◽  
pp. 12-18
Author(s):  
G. Bubyreva

The existing legislation determines the education as "an integral and focused process of teaching and upbringing, which represents a socially important value and shall be implemented so as to meet the interests of the individual, the family, the society and the state". However, even in this part, the meaning of the notion ‘socially significant benefit is not specified and allows for a wide range of interpretation [2]. Yet the more inconcrete is the answer to the question – "who and how should determine the interests of the individual, the family and even the state?" The national doctrine of education in the Russian Federation, which determined the goals of teaching and upbringing, the ways to attain them by means of the state policy regulating the field of education, the target achievements of the development of the educational system for the period up to 2025, approved by the Decree of the Government of the Russian Federation of October 4, 2000 #751, was abrogated by the Decree of the Government of the Russian Federation of March 29, 2014 #245 [7]. The new doctrine has not been developed so far. The RAE Academician A.B. Khutorsky believes that the absence of the national doctrine of education presents a threat to national security and a violation of the right of citizens to quality education. Accordingly, the teacher has to solve the problem of achieving the harmony of interests of the individual, the family, the society and the government on their own, which, however, judging by the officially published results, is the task that exceeds the abilities of the participants of the educational process.  The particular concern about the results of the patriotic upbringing served as a basis for the legislative initiative of the RF President V. V. Putin, who introduced the project of an amendment to the Law of RF "About Education of the Russian Federation" to the State Duma in 2020, regarding the quality of patriotic upbringing [3]. Patriotism, considered by the President of RF V. V. Putin as the only possible idea to unite the nation is "THE FEELING OF LOVE OF THE MOTHERLAND" and the readiness for every sacrifice and heroic deed for the sake of the interests of your Motherland. However, the practicing educators experience shortfalls in efficient methodologies of patriotic upbringing, which should let them bring up citizens, loving their Motherland more than themselves. The article is dedicated to solution to this problem based on the Value-sense paradigm of upbringing educational dynasty of the Kurbatovs [15].


2020 ◽  
Vol 2 (4) ◽  
pp. 126-130
Author(s):  
N. V. SHAMANIN ◽  

The article raises the issue of the relationship of parent-child relationships and professional preferences in pedagogical dynasties. Particular attention is paid to the role of the family in the professional development of the individual. It has been suggested that there is a relationship between parent-child relationships and professional preferences.


Author(s):  
Jon Stewart

This work represents a combination of different genres: cultural history, philosophical anthropology, and textbook. It follows a handful of different but interrelated themes through more than a dozen texts that were written over a period of several millennia. By means of an analysis of these texts, this work presents a theory about the development of Western Civilization from antiquity to the Middle Ages. The main line of argument traces the various self-conceptions of the different cultures as they developed historically. These self-conceptions reflect different views of what it is to be human. The thesis is that in these we can discern the gradual emergence of what we today call inwardness, subjectivity and individual freedom. As human civilization took its first tenuous steps, it had a very limited conception of the individual. Instead, the dominant principle was that of the wider group: the family, clan or people. Only in the course of history did the idea of what we know as individuality begin to emerge. It took millennia for this idea to be fully recognized and developed. The conception of human beings as having a sphere of inwardness and subjectivity subsequently had a sweeping impact on all aspects of culture, such as philosophy, religion, law, and art. Indeed, this conception largely constitutes what is today referred to as modernity. It is easy to lose sight of the fact that this modern conception of human subjectivity was not simply something given but rather the result of a long process of historical and cultural development.


Author(s):  
Karen Bennett

We frequently speak of certain things or phenomena being built out of or based in others. This soda can is made of molecules, which are in turn made of atoms, which are in turn made of subatomic particles. The behavior of a crowd is based in the behaviors of and interactions between individual people—it behaves as it does in virtue of the individual behaviors and interactions. Making Things Up concerns the family of relations that such talk appeals to, which Karen Bennett calls “building relations.” Grounding is one currently popular such relation; so too are composition, property realization, and—controversially—causation. Building relations connect more fundamental things (like atoms) to less fundamental things (like soda cans). But what are we even talking about when we say that something is more fundamental than something else? This book illuminates the ideas of building and fundamentality, as they are deployed in metaphysics and elsewhere in philosophy. Bennett paints a picture of a hierarchically structured world, and makes good sense of otherwise somewhat cryptic talk of “in virtue of” and fundamentality.


2021 ◽  
Vol 22 (11) ◽  
pp. 6000
Author(s):  
Sara Bertuzzi ◽  
Ana Gimeno ◽  
Ane Martinez-Castillo ◽  
Marta G. Lete ◽  
Sandra Delgado ◽  
...  

The interaction of multi-LacNAc (Galβ1-4GlcNAc)-containing N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers with human galectin-1 (Gal-1) and the carbohydrate recognition domain (CRD) of human galectin-3 (Gal-3) was analyzed using NMR methods in addition to cryo-electron-microscopy and dynamic light scattering (DLS) experiments. The interaction with individual LacNAc-containing components of the polymer was studied for comparison purposes. For Gal-3 CRD, the NMR data suggest a canonical interaction of the individual small-molecule bi- and trivalent ligands with the lectin binding site and better affinity for the trivalent arrangement due to statistical effects. For the glycopolymers, the interaction was stronger, although no evidence for forming a large supramolecule was obtained. In contrast, for Gal-1, the results indicate the formation of large cross-linked supramolecules in the presence of multivalent LacNAc entities for both the individual building blocks and the polymers. Interestingly, the bivalent and trivalent presentation of LacNAc in the polymer did not produce such an increase, indicating that the multivalency provided by the polymer is sufficient for triggering an efficient binding between the glycopolymer and Gal-1. This hypothesis was further demonstrated by electron microscopy and DLS methods.


2001 ◽  
Vol 8 (1) ◽  
pp. 31-34
Author(s):  
Allan Macinnes

This paper makes an important, interdisciplinary contribution, to the ongoing debate on the transition from clanship to capitalism. Integral to this contribution is the important distinction between capitalism as an individualist ideology and capitalist societies where individualism is a widespread but not necessarily a universal ideology. His concern is not with the bipolar opposition of landlord and people which tends to dominate debates on the land issue in the Highlands. Instead, he focuses on material culture change in relation to landscape organisation, settlement patterns and morphology in order to examine how social relationships were structured during the critical period of estate re-orientation often depicted progressively as Improvement but regressively as clearance through the removal and relocation of population. His case study on Kintyre is particularly valuable. By scrutinising spatial as well as social relationships Dalglish demonstrates that clanship was based as much on daily practices of living as on an patrimonial ideology of kinship, practices which led the House of Argyll to attempt the reinvention of concepts of occupancy in order to emphasise the importance of the individual over the family through partitioned space.


2021 ◽  
pp. 166923
Author(s):  
Fathima Nuzra Nagoor Pitchai ◽  
Akhil Chameettachal ◽  
Valérie Vivet-Boudou ◽  
Lizna Mohamed Ali ◽  
Vineeta N. Pillai ◽  
...  

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