The relationship between conserved structural motifs and their biological function in the virus replication cycle is the interest of many researchers around the world. RNA structure is closely ...related to RNA function. Therefore, technological progress in high-throughput approaches for RNA structure analysis and the development of new ones are very important. In this mini review, we discuss a few perspectives on the structural elements of viral genomes and some methods used for RNA structure prediction and characterization. Based on the recent literature, we describe several examples of studies concerning the viral genomes, especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV). Herein, we emphasize that a better understanding of viral genome architecture allows for the discovery of the structure-function relationship, and as a result, the discovery of new potential antiviral therapeutics.
The book Approaches to Death and Dying: Bioethical and Cultural Perspectives , edited by Marta Szabat and Jan Piasecki, is part of a still too narrow catalogue of works devoted to end-of-life themes. ...The volume consists of eleven articles arranged in four parts corresponding to a broad range of issues: law, ethics, philosophy, and cultural studies. The arrangement of the book is thus constructed around various perspectives upon which any reflection on death and dying must be based. This is perhaps indicative of how difficult it is to adopt an unambiguous attitude towards death-modernity, which introduces a multitude of possible choices and decisions regarding our own bodies, has enhanced individualism but at the same time done away with the order provided by old customs, cultural arrangements, strategies towards the inevitable and the power exerted by that order.
Influenza A virus (IAV) causes seasonal epidemics and sporadic pandemics, therefore is an important research subject for scientists around the world. Despite the high variability of its genome, the ...structure of viral RNA (vRNA) possesses features that remain constant between strains and are biologically important for virus replication. Therefore, conserved structural motifs of vRNA can represent a novel therapeutic target. Here, we focused on the presence of G-rich sequences within the influenza A/California/07/2009(H1N1) genome and their ability to form RNA G-quadruplex structures (G4s). We identified 12 potential quadruplex-forming sequences (PQS) and determined their conservation among the IAV strains using bioinformatics tools. Then we examined the propensity of PQS to fold into G4s by various biophysical methods. Our results revealed that six PQS oligomers could form RNA G-quadruplexes. However, three of them were confirmed to adopt G4 structures by all utilized methods. Moreover, we showed that these PQS motifs are present within segments encoding polymerase complex proteins indicating their possible role in the virus biology.
This article concerns events of the Old Testament – Yahweh commands Abraham to sacrifice his only son – Isaac – on Mount Moriah. This passage from the Old Testament, from the Book of Genesis, became ...the basis of Søren Kierkegaard’s considerations in Fear and Trembling. In the text I refer to, on the one hand, Kierkegaard’s considerations, while on the other hand I try to identify other possible interpretive tropes that could be useful, for example, during classes on the subject of faith or the status of ethical dilemmas in the modern world.
Abstract
There is increasing interest in the roles of covalently modified nucleotides in RNA. There has been, however, an inability to account for modifications in secondary structure prediction ...because of a lack of software and thermodynamic parameters. We report the solution for these issues for N
6
-methyladenosine (m
6
A), allowing secondary structure prediction for an alphabet of A, C, G, U, and m
6
A. The RNAstructure software now works with user-defined nucleotide alphabets of any size. We also report a set of nearest neighbor parameters for helices and loops containing m
6
A, using experiments. Interestingly, N
6
-methylation decreases folding stability for adenosines in the middle of a helix, has little effect on folding stability for adenosines at the ends of helices, and increases folding stability for unpaired adenosines stacked on a helix. We demonstrate predictions for an N
6
-methylation-activated protein recognition site from MALAT1 and human transcriptome-wide effects of N
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-methylation on the probability of adenosine being buried in a helix.
The occurrence of triplexes in vivo has been well documented and is determined by the presence of long homopurine-homopyrimidine tracts. The formation of these structures is the result of ...conformational changes that occur in the duplex, which allow the binding of a third strand within the major groove of the helix. Formation of these noncanonical forms by introducing synthetic triplex-forming oligonucleotides (TFOs) into the cell may have applications in molecular biology, diagnostics and therapy. This study focused on the formation of RNA triplexes as well as their thermal stability and biological potential in the HeLa cell line. Thermodynamics studies revealed that the incorporation of multiple locked nucleic acid (LNA) and 2-thiouridine (2-thioU) residues increased the stability of RNA triplexes. These data suggest that the number and position of the modified nucleotides within TFOs significantly stabilize the formed structures. Moreover, specificity of the interactions between the modified TFOs and the RNA hairpin was characterized using electrophoretic mobility-shift assay (EMSA), and triplex dissociation constants have been also determined. Finally, through quantitative analysis of GFP expression, the triplex structures were shown to regulate GFP gene silencing. Together, our data provide a first glimpse into the thermodynamic, structural and biological properties of LNA- and 2-thioU modified RNA triplexes.
Correspondence to Dr Marta Szabat, Health Sciences, Philosophy and Bioethics, Jagiellonian University Medical College, Krakow, Poland; mszab@poczta.fm The concept of ethical preparedness (EP), ...defined as a set of practices in genomic medicine aimed not only at efficiently managing sensitive issues in the laboratory but also at ensuring adherence to ethical principles,1 has potential benefits for clinical laboratory scientists, contingent on three key conditions. The important thing is to recognise that while laboratory results may possess prospective value for future generations, genomic medicine addresses the clinical needs of present and potentially vulnerable patients. ...when interpreting the clinical relevance of the information provided to patients, the potential risk of harm should be weighed alongside the access to comprehensive explanations, including the possibility that the laboratory may refuse to disclose information to the patient. ...efforts should be made to standardise professional procedures and ethical guidelines in laboratories.
This article examines the compatibility and relevance of Gabriel Marcel’s phenomenology of hope in interdisciplinary research on the role of hope in end-of-life (EOL) care. Our analysis is divided ...into three thematic topics which examine the various shades of hope observed in Marcel’s phenomenology of hope and in the collection of 20 EOL studies on hope as experienced by adult palliative care (PC) patients, health care professionals (HCP) and parents of terminally ill children. The three topics defining the shades of hope are: the meaning of hope in its dynamic aspects, the dialectics of hope and despair, and the transcendent facets of hope. We analyse how Marcel’s understanding of hope is reflected in EOL studies, and how this perception can enrich the philosophy of PC and significantly deepen and broaden HCPs’ understanding of hope. Our findings prove that despite terminological differences between Marcelian phenomenology and the concepts of hope in the 20 EOL studies, hope emerges as a resourceful movement towards being. Implementing Marcelian hope within communication in EOL care could help in HCPs’ interpersonal approach to patients as his concept harbors a holistic perception of the existential situation of a person. Equally, introducing Marcel’s phenomenology of hope into the clinical encounter could play a beneficial role in improving the ability of patients to adapt to the difficult conditions of their disease and PC treatment.
The study discusses a new approach to parental agency in pediatric palliative care based on an active form of caregiving. It also explores the possibility of a positive conceptualization of parental ...agency in its relational context. The paper begins with an illustrative case study based on a clinical situation. This is followed by an analysis of various aspects of parental agency based on empirical studies that disclose the insufficiencies of the traditional approach to parental agency. In the next step, parental agency is analyzed from a reality‐based perspective as an activity focused on relationships and the cognitive capacity of parents vis‐a‐vis their seriously ill children. The paper also considers the importance of the cultural and social contexts in which parental agency and decision‐making take place. This agency is addressed not as individualistic in form, and nor is it exercised in terms of fixed choices. Rather, the focus is on its dynamic and future‐oriented aspects. Consequently, parental agency should be comprehended not only as a form of proxy agency representing the child's best interests but also as a complex decision‐making process in which the parents learn from their child how to become good, compassionate caregivers and at the same time good parents.
This is the first report to provide comprehensive thermodynamic and structural data concerning duplex, hairpin, quadruplex and i-motif structures in β-L-RNA series. Herein we confirm that, within the ...limits of experimental error, the thermodynamic stability of enantiomeric structural motifs is the same as that of naturally occurring D-RNA counterparts. In addition, formation of D-RNA/L-RNA heterochiral duplexes is also observed; however, their thermodynamic stability is significantly reduced in reference to homochiral D-RNA duplexes. The presence of three locked nucleic acid (LNA) residues within the D-RNA strand diminishes the negative effect of the enantiomeric, complementary L-RNA strand in the formation of heterochiral RNA duplexes. Similar behavior is also observed for heterochiral LNA-2'-O-methyl-D-RNA/L-RNA duplexes. The formation of heterochiral duplexes was confirmed by 1H NMR spectroscopy. The CD curves of homochiral L-RNA structural motifs are always reversed, whereas CD curves of heterochiral duplexes present individual features dependent on the composition of chiral strands.
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