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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive single-stranded RNA virus, engages in complex interactions with host cell proteins throughout its life cycle. While these interactions enable the host to recognize and inhibit viral replication, they also facilitate essential viral processes such as transcription, translation, and replication. Many aspects of these virus-host interactions remain poorly understood. Here, we employed the catRAPID algorithm and utilized the RNA-protein interaction detection coupled with mass spectrometry technology to predict and validate the host proteins that specifically bind to the highly structured 5′ and 3′ terminal regions of the SARS-CoV-2 RNA. Among the interactions identified, we prioritized pseudouridine synthase PUS7, which binds to both ends of the viral RNA. Using nanopore direct RNA sequencing, we discovered that the viral RNA undergoes extensive post-transcriptional modifications. Modified consensus regions for PUS7 were identified at both terminal regions of the SARS-CoV-2 RNA, including one in the viral transcription regulatory sequence leader. Collectively, our findings offer insights into host protein interactions with the SARS-CoV-2 UTRs and highlight the likely significance of pseudouridine synthases and other post-transcriptional modifications in the viral life cycle. This new knowledge enhances our understanding of virus-host dynamics and could inform the development of targeted therapeutic strategies.

IntroductionHeartburn pathogenesis in GERD remains incompletely understood. We aimed to identify differences in the immune cell signature and sensory mucosal markers between reflux phenotypes and healthy asymptomatic subjects.MethodsThirty-seven patients with heartburn symptoms were phenotyped endoscopically and with objective reflux studies into erosive reflux disease (ERD) (N=10), nonerosive reflux disease (NERD) (N=9), functional heartburn (FH) (N=9), and Barrett’s esophagus (BO) (N=9). Bulk mRNA-sequencing(RNA-seq) was conducted on RNA extracted from endoscopic biopsies, and immune cell deconvolution analysis was performed using CIBERSORT. RNA-seq findings were validated by immunofluorescent staining for CD1a, nerve growth factor (NGF), and mast cell tryptase in corresponding patient biopsies.ResultsTranscriptomic analysis detected higher mast cell abundance in BO, ERD, and NERD compared to healthy controls (p

Abstract Background Patient‐Reported Experience Measures (PREMs) are key in improving healthcare quality, but no PREM exists for inflammatory bowel disease (IBD). This study aimed to co‐produce a PREM with IBD service users for IBD service evaluation and quality improvement programme. Methods A pool of 75 items was drawn from published survey instruments covering interactions with services and aspects of living with IBD. In Stage 1, during two workshops, eight expert service users reduced candidate items through a ranked‐choice voting exercise and suggested further items. During Stage 2, 18 previously uninvolved people with IBD assessed the face and content validity of the candidate items in ‘Think Aloud’ interviews. During two final workshops (Stage 3), the expert service users removed, modified and added items based on the interview findings to produce a final version of the PREM. Results Stage 1 generated a draft working PREM mapped to the following four domains: Patient‐Centred Care; Quality; Accessibility; Communication and Involvement. The PREM included a set of nine items created by the expert group which shifted the emphasis from ‘self‐management’ to ‘living with IBD’. Stage 2 interviews showed that comprehension of the PREM was very good, although there were concerns about the wording, IBD‐relevance and ambiguity of some items. During the final two workshops in Stage 3, the expert service users removed 7 items, modified 15 items and added seven new ones based on the interview findings, resulting in a 38‐item PREM. Conclusions This study demonstrates how extensive service user involvement can inform PREM development. Patient or Public Contribution Patients were involved as active members of the research team and as research participants to co‐produce and validate a PREM for IBD services. In Stage 1, eight expert service users (‘the expert group’) reduced candidate items for the PREM through a voting exercise and suggested new items. During Stage 2, 18 previously uninvolved people with IBD (the ‘think aloud’ participants) assessed the validity of the candidate items in ‘Think Aloud’ interviews as research participants. In Stage 3, the expert group removed, changed and added items based on the interview findings to produce a final version of the 38‐item PREM. This study shows how service user involvement can meaningfully inform PREM development.

Marine protected areas are proposed to protect elasmobranchs (sharks, skates, and rays) but the fishing impact from small-scale fisheries in these areas is unknown. From 1256 fishing operations carried out in partially protected and unprotected areas in six Mediterranean countries, this study shows that catches were higher in partially protected areas than in unprotected areas, indicating poor small-scale fisheries management as a threat for these species.

Holothurians or sea cucumbers are key organisms in marine ecosystems that, by ingesting large quantities of sediments, provide important ecosystem services. Among them, Parastichopus regalis (Cuvier, 1817) is one of the living sea cucumbers in the Mediterranean actively fished for human consumption mainly in Spain, where it is considered a gastronomic delicacy. In the Strait of Sicily (central Mediterranean Sea), this species is not exploited for commercial use even if it is used as bait by longline fishery. P. regalis is frequently caught by bottom trawling and discarded at sea by fishers after catch, and because of its capacity to resist air exposition (at least in cold months), it is reasonable to consider that it is not affected by fishing mortality. Having observed a significant decrease in abundance since 2018, the possible effects of some ecological factors related to current climate change (i.e., temperature and pH) were sought. Generalized additive models (GAMs) were applied to investigate the relationship among the abundance of P. regalis and environmental variables and fishing effort. Long time series of P. regalis densities (2008–2021) were extracted from the MEDITS bottom trawling survey and modeled as function of environmental parameters (i.e., salinity, dissolved oxygen, ammonium, pH, and chlorophyll α) and fishing effort (i.e., total number of fishing days per gross tonnage). Our results showed that this species prefers the soft bottoms (50–200 m) of the Adventure Bank and Malta Plateau, and its distribution changed over time with a slight deepening and a rarefaction of spatial distribution starting from 2011 and 2017, respectively. In addition, a positive relationship with pH concentration in surface waters during the larval dispersal phase (3-year lag before the survey) and nutrient concentration at sea bottom (1-year lag) has been found, suggesting that this species is sensitive to climate change and food availability. This study adds new knowledge about the population dynamics of an unexploited stock of P. regalis under fishing impact and environmental under climate change in fisheries management.

Additive manufacturing technologies have been increasingly applied to the development of radio frequency components in the past few years. Indeed, the free-form capability of these processes allows for the design of novel components, whose actual implementation through conventional machining is rather complex or even not possible. This paper describes a monolithic WR51 component integrating three radio frequency functionalities, namely, bending, twisting, and filtering. Three aluminum prototypes with different bending/twisting radii have been manufactured through the selective laser melting process. They exhibit a measured rejection higher than 60 dB in 17.5 and 21.2 GHz, and a measured return loss better than 20 dB in 12.5 and 15 GHz. Significant mass and envelope reductions (higher than 60% depending on the bending/twisting radius) with respect to the reference subsystem with distinct waveguide components are achieved. These results assess the effectiveness of 3-D metal printing in the miniaturization and integration of waveguide systems. [ABSTRACT FROM PUBLISHER]