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Internal ribosome entry is a key mechanism for viral protein synthesis in a subset of RNA viruses. Cricket paralysis virus (CrPV), a member of Dicistroviridae, has a positive-sense single strand RNA genome that contains two internal ribosome entry sites (IRES), a 51 untranslated region (51UTR) and intergenic region (IGR) IRES, that direct translation of open reading frames (ORF) encoding the viral non-structural and structural proteins, respectively. The regulation of and the significance of the CrPV IRESs during infection are not fully understood. In this study, using a series of biochemical assays including radioactive-pulse labelling, reporter RNA assays and ribosome profiling, we demonstrate that while 51UTR IRES translational activity is constant throughout infection, IGR IRES translation is delayed and then stimulated two to three hours post infection. The delay in IGR IRES translation is not affected by inhibiting global translation prematurely via treatment with Pateamine A. Using a CrPV replicon that uncouples viral translation and replication, we show that the increase in IGR IRES translation is dependent on expression of non-structural proteins and is greatly stimulated when replication is active. Temporal regulation by distinct IRESs within the CrPV genome is an effective viral strategy to ensure optimal timing and expression of viral proteins to facilitate infection. [ABSTRACT FROM AUTHOR]

Internal ribosome entry is a key mechanism for viral protein synthesis in a subset of RNA viruses. Cricket paralysis virus (CrPV), a member of Dicistroviridae, has a positive-sense single strand RNA genome that contains two internal ribosome entry sites (IRES), a 51untranslated region (51UTR) and intergenic region (IGR) IRES, that direct translation of open reading frames (ORF) encoding the viral non-structural and structural proteins, respectively. The regulation of and the significance of the CrPV IRESs during infection are not fully understood. In this study, using a series of biochemical assays including radioactive-pulse labelling, reporter RNA assays and ribosome profiling, we demonstrate that while 51UTR IRES translational activity is constant throughout infection, IGR IRES translation is delayed and then stimulated two to three hours post infection. The delay in IGR IRES translation is not affected by inhibiting global translation prematurely via treatment with Pateamine A. Using a CrPV replicon that uncouples viral translation and replication, we show that the increase in IGR IRES translation is dependent on expression of non-structural proteins and is greatly stimulated when replication is active. Temporal regulation by distinct IRESs within the CrPV genome is an effective viral strategy to ensure optimal timing and expression of viral proteins to facilitate infection. [ABSTRACT FROM AUTHOR]

Introduction: Both hearing loss and dementia are associated with ageing, and it is thought that many individuals living with dementia also live with hearing loss. Despite the large comorbidity between these two disorders, there remains a clear lack of established guidelines in audiological services for assessing and managing patients living with dementia. This scoping review aims to examine whether specialist clinical pathways exist in audiology services for people living with coexisting hearing loss and dementia and to describe the specific components and features of these pathways. This review will provide up-to-date information on clinical practice, identifying any gaps in care and in the literature to inform future research hypotheses and best practice guidelines., Methods and Analysis: The methods are reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. The following electronic databases will be searched: CINAHL, EMBASE, MEDLINE, PsycINFO, PubMed, Scopus and Web of Science. The eligibility criteria are defined according to the domains of the SPIDER (Sample, Phenomenon of Interest, Design, Evaluation and Research type) search strategy tool. Primary research studies and select grey literature sources (eg, practice guidelines) will be eligible if published within the last 15 years. Studies eligible for inclusion must contain adults living with suspected or confirmed dementia, their carers, or clinicians within audiology services. Initial searches were performed on 31 January 2024 and will be updated before completion and submission of the review. Article quality will be appraised using an established tool: the Mixed Methods Appraisal Tool. The results will be synthesised and reported in line with reflexive thematic analysis guidelines., Ethics and Dissemination: No ethical issues are foreseen as the review will collect secondary data only. Findings will be reported by peer-reviewed publication and by national and international academic conferences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ Group.)

This paper describes the program ASSAM, which has been developed to search for patterns of amino acid side-chains in the 3D structures in the Protein Data Bank. ASSAM represents an amino acid by a vector drawn from the main chain towards the functional part of the amino acid and then computes a graph representation of a protein in which the individual side-chain vectors are the nodes and the intervector distances are the edges. The presence of a query pattern in a Protein Data Bank structure can then be searched for by means of a subgraph isomorphism algorithm. Recent enhancements to ASSAM allow searches to include the following: the main-chain structure in addition to the side-chains; the secondary structure and solvent accessibility of side-chains; allowable distances from a known binding-site; disulfide bridges; and improved generic and wild-card queries. The effectiveness of these approaches is demonstrated by extensive searches of the Protein Data Bank for typical 3D query patterns.