Functional domains of the influenza A virus PB2 protein:identification of NP- and PB1-binding sites

AbstractInfluenza virus genomic RNA segments are packaged into ribonucleoprotein (RNP) structures by the PB1, PB2, and PA subunits of an RNA polymerase and a single-strand RNA-binding nucleoprotein (NP). Assembly and function of these ribonucleoproteins depend on a complex set of protein–protein and protein–RNA interactions. Here, we identify new functional domains of PB2. We show that PB2 contains two regions that bind NP and also identify a novel PB1 binding site. The regions of PB2 responsible for binding NP and PB1 show considerable overlap, and binding of NP to the PB2 fragments could be outcompeted by PB1. The binding domains of PB2 acted as trans-dominant inhibitors of viral gene expression, and consistent with the in vitro binding data, their inhibitory activity depended on the concentration of wild-type PB2, NP, and PB1. This provides evidence for functionally significant and potentially regulatory interactions between PB2 and NP

Healing the civic body:Forensic investigation and biopolitical strategies in Flemish towns, 1250-1500

Peace procedures, called Zoendingen in Dutch sources or Apaisement in French ones, were procedures of reconciliation, used in the County of Flanders from the thirteenth century onwards. At the urban level, they operated as a law court aimed to mediate conflicts between citizens. Many type of altercations could lead to violence, although actors generally fought to protect their honour and status, and that of their kinship group. Peace procedures represented an honorable alternative to violence, which promoted community well-being and social cohesion, by awarding honorable and financial compensations to citizens. The first chapter describes the legal structure of Ghent and Douai, on which this dissertation is focused, to highlight the interests that led urban governments to deploy such legal infrastructures. The next chapter explores the notion of citizenship, to identify how individuals and groups were perceived by urban authorities. Chapter three investigates how the mechanisms of the court could effectively compensate the loss of honor, and how this notion was linked to health at several levels. The following chapter establishes the court’s reliance on the expertise of medical professionals, which in turn increased medical professional’s prestige. It then shows how Flemish governments integrated notions of labor and communal well-being into their perception of the body, using the knowledge produced medical professionals in court to manage the city’s life forces and promote what they defined as the common good. The final chapter demonstrates that Flemish municipal government partook in biopolitical negotiations, seeking to control, police and monopolize the city’s medical market, and by doing so, were led to rethink political power distribution in their cities

Healing the civic body:Forensic investigation and biopolitical strategies in Flemish towns, 1250-1500

Peace procedures, called Zoendingen in Dutch sources or Apaisement in French ones, were procedures of reconciliation, used in the County of Flanders from the thirteenth century onwards. At the urban level, they operated as a law court aimed to mediate conflicts between citizens. Many type of altercations could lead to violence, although actors generally fought to protect their honour and status, and that of their kinship group. Peace procedures represented an honorable alternative to violence, which promoted community well-being and social cohesion, by awarding honorable and financial compensations to citizens. The first chapter describes the legal structure of Ghent and Douai, on which this dissertation is focused, to highlight the interests that led urban governments to deploy such legal infrastructures. The next chapter explores the notion of citizenship, to identify how individuals and groups were perceived by urban authorities. Chapter three investigates how the mechanisms of the court could effectively compensate the loss of honor, and how this notion was linked to health at several levels. The following chapter establishes the court’s reliance on the expertise of medical professionals, which in turn increased medical professional’s prestige. It then shows how Flemish governments integrated notions of labor and communal well-being into their perception of the body, using the knowledge produced medical professionals in court to manage the city’s life forces and promote what they defined as the common good. The final chapter demonstrates that Flemish municipal government partook in biopolitical negotiations, seeking to control, police and monopolize the city’s medical market, and by doing so, were led to rethink political power distribution in their cities

Compositional biases in RNA viruses::causes, consequences and applications

If each of the four nucleotides were represented equally in the genomes of viruses and the hosts they infect, each base would occur at a frequency of 25%. However, this is not observed in nature. Similarly, the order of nucleotides is not random (e.g., in the human genome, guanine follows cytosine at a frequency of ~0.0125, or a quarter the number of times predicted by random representation). Codon usage and codon order are also nonrandom. Furthermore, nucleotide and codon biases vary between species. Such biases have various drivers, including cellular proteins that recognize specific patterns in nucleic acids, that once triggered, induce mutations or invoke intrinsic or innate immune responses. In this review we examine the types of compositional biases identified in viral genomes and current understanding of the evolutionary mechanisms underpinning these trends. Finally, we consider the potential for large scale synonymous recoding strategies to engineer RNA virus vaccines, including those with pandemic potential, such as influenza A virus and Severe Acute Respiratory Syndrome Coronavirus Virus 2. This article is categorized under: RNA in Disease and Development > RNA in Disease. RNA Evolution and Genomics > Computational Analyses of RNA. RNA Interactions with Proteins and Other Molecules > Protein‐RNA Recognition

Bilingualism in autism:Evidence and recommendations for education practice

This guidance document summarises the latest findings in the field of bilingualism in autism research. This summary focuses on the information needed by educators to provide up-to-date and adapted advice to bilingual families of autistic children and young people

Bilingualism in autism:Evidence and recommendations for clinical practice

This guidance document summarises the latest findings in the field of bilingualism in autism research. This summary focuses on the information needed by clinicians to provide up-to-date and adapted advice to bilingual families of autistic children and young people. This resource has been endorsed by the UK Royal College of Speech and Language Therapists

A functional link between the actin cytoskeleton and lipid rafts during budding of filamentous influenza virions

AbstractMorphogenesis of influenza virus is a poorly understood process that produces two types of enveloped virion: ∼100-nm spheres and similar diameter filaments that reach 20 μm in length. Spherical particles assemble at plasma membrane lipid rafts in a process independent of microfilaments. The budding site of filamentous virions is hitherto uncharacterised but their formation involves the actin cytoskeleton. We confirm microfilament involvement in filamentous budding and show that after disruption of cortical actin by jasplakinolide, HA, NP, and M1 redistributed around β-actin clusters to form novel annular membrane structures. HA in filamentous virions and jasplakinolide-induced annuli was detergent insoluble at 4°C. Furthermore, in both cases HA partitioned into low buoyant density detergent-insoluble glycolipid domains, indicating that filamentous virions and annuli contain reorganised lipid rafts. We propose that the actin cytoskeleton is required to maintain the correct organisation of lipid rafts for incorporation into budding viral filaments

Bringing together autism and bilingualism research:Language matters

Please note this paper has been published ahead of print in Linguistic Approaches to Bilingualism: Digard, B. G., & Sorace, A. (2021). Bringing together autism and bilingualism research: Language matters. Linguistic Approaches to Bilingualism. https://doi.org/10.1075/lab.21071.dig Please do not cite this preprint. - (Commentary to keynote by Philippe Prevost and Laurice Tuller, “Bilingual language development in autism”