A new family of bacterial ribosome hibernation factors.

To conserve energy during starvation and stress, many organisms use hibernation factor proteins to inhibit protein synthesis and protect their ribosomes from damage1,2. In bacteria, two families of hibernation factors have been described, but the low conservation of these proteins and the huge diversity of species, habitats and environmental stressors have confounded their discovery3-6. Here, by combining cryogenic electron microscopy, genetics and biochemistry, we identify Balon, a new hibernation factor in the cold-adapted bacterium Psychrobacter urativorans. We show that Balon is a distant homologue of the archaeo-eukaryotic translation factor aeRF1 and is found in 20% of representative bacteria. During cold shock or stationary phase, Balon occupies the ribosomal A site in both vacant and actively translating ribosomes in complex with EF-Tu, highlighting an unexpected role for EF-Tu in the cellular stress response. Unlike typical A-site substrates, Balon binds to ribosomes in an mRNA-independent manner, initiating a new mode of ribosome hibernation that can commence while ribosomes are still engaged in protein synthesis. Our work suggests that Balon-EF-Tu-regulated ribosome hibernation is a ubiquitous bacterial stress-response mechanism, and we demonstrate that putative Balon homologues in Mycobacteria bind to ribosomes in a similar fashion. This finding calls for a revision of the current model of ribosome hibernation inferred from common model organisms and holds numerous implications for how we understand and study ribosome hibernation.

The effects of communicating uncertainty around statistics, on public trust.

Uncertainty around statistics is inevitable. However, communicators of uncertain statistics, particularly in high-stakes and potentially political circumstances, may be concerned that presenting uncertainties could undermine the perceived trustworthiness of the information or its source. In a large survey experiment (Study 1; N = 10 519), we report that communicating uncertainty around present COVID-19 statistics in the form of a numeric range (versus no uncertainty) may lead to slightly lower perceived trustworthiness of the number presented but has no impact on perceived trustworthiness of the source of the information. We also show that this minimal impact of numeric uncertainty on trustworthiness is also present when communicating future, projected COVID-19 statistics (Study 2; N = 2,309). Conversely, we find statements about the mere existence of uncertainty, without quantification, can reduce both perceived trustworthiness of the numbers and of their source. Our findings add to others suggesting that communicators can be transparent about statistical uncertainty without undermining their credibility as a source but should endeavour to provide a quantification, such as a numeric range, where possible.

The induction of p53 correlates with defects in the production, but not the levels, of the small ribosomal subunit and stalled large ribosomal subunit biogenesis.

Ribosome biogenesis is one of the biggest consumers of cellular energy. More than 20 genetic diseases (ribosomopathies) and multiple cancers arise from defects in the production of the 40S (SSU) and 60S (LSU) ribosomal subunits. Defects in the production of either the SSU or LSU result in p53 induction through the accumulation of the 5S RNP, an LSU assembly intermediate. While the mechanism is understood for the LSU, it is still unclear how SSU production defects induce p53 through the 5S RNP since the production of the two subunits is believed to be uncoupled. Here, we examined the response to SSU production defects to understand how this leads to the activation of p53 via the 5S RNP. We found that p53 activation occurs rapidly after SSU production is blocked, prior to changes in mature ribosomal RNA (rRNA) levels but correlated with early, middle and late SSU pre-rRNA processing defects. Furthermore, both nucleolar/nuclear LSU maturation, in particular late stages in 5.8S rRNA processing, and pre-LSU export were affected by SSU production defects. We have therefore uncovered a novel connection between the SSU and LSU production pathways in human cells, which explains how p53 is induced in response to SSU production defects.

The Misinformation Susceptibility Test (MIST): A psychometrically validated measure of news veracity discernment.

Interest in the psychology of misinformation has exploded in recent years. Despite ample research, to date there is no validated framework to measure misinformation susceptibility. Therefore, we introduce Verification done, a nuanced interpretation schema and assessment tool that simultaneously considers Veracity discernment, and its distinct, measurable abilities (real/fake news detection), and biases (distrust/naïvité-negative/positive judgment bias). We then conduct three studies with seven independent samples (Ntotal = 8504) to show how to develop, validate, and apply the Misinformation Susceptibility Test (MIST). In Study 1 (N = 409) we use a neural network language model to generate items, and use three psychometric methods-factor analysis, item response theory, and exploratory graph analysis-to create the MIST-20 (20 items; completion time < 2 minutes), the MIST-16 (16 items; < 2 minutes), and the MIST-8 (8 items; < 1 minute). In Study 2 (N = 7674) we confirm the internal and predictive validity of the MIST in five national quota samples (US, UK), across 2 years, from three different sampling platforms-Respondi, CloudResearch, and Prolific. We also explore the MIST's nomological net and generate age-, region-, and country-specific norm tables. In Study 3 (N = 421) we demonstrate how the MIST-in conjunction with Verification done-can provide novel insights on existing psychological interventions, thereby advancing theory development. Finally, we outline the versatile implementations of the MIST as a screening tool, covariate, and intervention evaluation framework. As all methods are transparently reported and detailed, this work will allow other researchers to create similar scales or adapt them for any population of interest.

RPS27a and RPL40, Which Are Produced as Ubiquitin Fusion Proteins, Are Not Essential for p53 Signalling.

Two of the four human ubiquitin-encoding genes express ubiquitin as an N-terminal fusion precursor polypeptide, with either ribosomal protein (RP) RPS27a or RPL40 at the C-terminus. RPS27a and RPL40 have been proposed to be important for the induction of the tumour suppressor p53 in response to defects in ribosome biogenesis, suggesting that they may play a role in the coordination of ribosome production, ubiquitin levels and p53 signalling. Here, we report that RPS27a is cleaved from the ubiquitin-RP precursor in a process that appears independent of ribosome biogenesis. In contrast to other RPs, the knockdown of either RPS27a or RPL40 did not stabilise the tumour suppressor p53 in U2OS cells. Knockdown of neither protein blocked p53 stabilisation following inhibition of ribosome biogenesis by actinomycin D, indicating that they are not needed for p53 signalling in these cells. However, the knockdown of both RPS27a and RPL40 in MCF7 and LNCaP cells robustly induced p53, consistent with observations made with the majority of other RPs. Importantly, RPS27a and RPL40 are needed for rRNA production in all cell lines tested. Our data suggest that the role of RPS27a and RPL40 in p53 signalling, but not their importance in ribosome biogenesis, differs between cell types.

Weight loss associated with low-energy diets with different glycaemic loads does not improve arterial stiffness: a randomised clinical trial.

We evaluated the effects of two low-energy diets with different glycaemic loads on arterial stiffness in adults with excess weight. This was a 45-day parallel-group, randomised clinical trial including seventy-five participants (20-59 years; BMI 32 kg/m2). They were assigned to two similar low-energy diets (reduction of ∼750 kcal.d-1) with macronutrient composition (55 % carbohydrates, 20 % proteins and 25 % lipids) but different glycaemic loads: high-glycaemic load (HGL 171 g.d-1; n 36) or low-glycaemic load (LGL 67 g.d-1; n 39). We evaluated: arterial stiffness (pulse wave velocity, PWV); augmentation index (AIx@75); reflection coefficient; fasting blood glucose; fasting lipid profile; blood pressure and body composition. We found no improvements in PWV (P = 0·690) and AIx@75 (P = 0·083) in both diet groups, but there was a decrease in the reflection coefficient in the LGL group (P = 0·003) compared with baseline. The LGL diet group showed reductions in body weight (Δ -4·9 kg; P = 0·001), BMI (Δ -1·6 kg/m2; P = 0·001), waist circumference (Δ -3·1 cm; P = 0·001), body fat (Δ -1·8 %; P = 0·034), as well as TAG (Δ -14·7 mg/dl; P = 0·016) and VLDL (Δ -2·8 mg/dl; P = 0·020). The HGL diet group showed a reduction in total cholesterol (Δ -14·6 mg/dl; P = 0·001), LDL (Δ -9·3 mg/dl; P = 0·029) but a reduction in HDL (Δ -3·7 mg/dl; P = 0·002). In conclusion, a 45-day intervention with low-energy HGL or LGL diets in adults with excess weight was not effective to improve arterial stiffness. However, the LGL diet intervention was associated with a reduction of reflection coefficient and improvements in body composition, TAG and VLDL levels.

Relationship Between Dual-Energy X-Ray Absorptiometry, Ultrasonography, and Anthropometry Methods to Estimate Muscle Mass and Muscle Quality in Older Adults.

Decreased muscle quality (MQ) may explain functional capacity impairments during aging. Thus, it is essential to verify the interaction between MQ and functional capacity in older adults. We investigated the relationship between MQ and functional capacity in older adults (n = 34; 66.3 ± 4.6 year). MQ was estimated by maximum strength of knee extensors normalized to thigh muscle mass. Maximum strength was assessed on an isokinetic dynamometer (peak torque), while dual-energy X-ray absorptiometry (DXA), ultrasonography, and anthropometry were used to determine thigh muscle mass. Functional capacity was verified by 30-s sit to stand and timed up and go tests. Significant correlations were found between MQ assessed by DXA with 30-s sit to stand (r = .35; p < .05) and timed up and go (r = -.47; p < .05), and MQ assessed by anthropometry with timed up and go (r = -.41; p < .05), but not between MQ assessed by ultrasonography with functional capacity (p > .05). No significant relationship between muscle mass with functional capacity was observed. Thus, MQ assessed by DXA and MQ assessed by anthropometry may partially explain functional capacity in older adults. Interestingly, muscle mass alone did not explain performance in functional tests in this population.

Caught in the act-Visualizing ribonucleases during eukaryotic ribosome assembly.

Ribosomes are essential macromolecular machines responsible for translating the genetic information encoded in mRNAs into proteins. Ribosomes are composed of ribosomal RNAs and proteins (rRNAs and RPs) and the rRNAs fulfill both catalytic and architectural functions. Excision of the mature eukaryotic rRNAs from their precursor transcript is achieved through a complex series of endoribonucleolytic cleavages and exoribonucleolytic processing steps that are precisely coordinated with other aspects of ribosome assembly. Many ribonucleases involved in pre-rRNA processing have been identified and pre-rRNA processing pathways are relatively well defined. However, momentous advances in cryo-electron microscopy have recently enabled structural snapshots of various pre-ribosomal particles from budding yeast (Saccharomyces cerevisiae) and human cells to be captured and, excitingly, these structures not only allow pre-rRNAs to be observed before and after cleavage events, but also enable ribonucleases to be visualized on their target RNAs. These structural views of pre-rRNA processing in action allow a new layer of understanding of rRNA maturation and how it is coordinated with other aspects of ribosome assembly. They illuminate mechanisms of target recognition by the diverse ribonucleases involved and reveal how the cleavage/processing activities of these enzymes are regulated. In this review, we discuss the new insights into pre-rRNA processing gained by structural analyses and the growing understanding of the mechanisms of ribonuclease regulation. This article is categorized under: Translation > Ribosome Biogenesis RNA Processing > rRNA Processing.

COVID-19 risk perception and hoax beliefs in the US immediately before and after the announcement of President Trump's diagnosis.

A notable challenge of the SARS-CoV-2 pandemic has been public scepticism over the severity of the disease, or even its existence. Such scepticism is politically skewed in the USA, with conservatives more likely to downplay or deny the risks of the virus. However, the hospitalization of President Trump with COVID-19 in October 2020 served as a high-profile exemplar of the reality and risks of the virus, and as such may have influenced opinions, particularly for US conservatives. We investigate whether President Trump testing positive was associated with changes in public attitudes towards the virus. In two studies, we surveyed independent representative US samples before and after the announcement of Trump's illness. In Study 1, measuring risk perceptions of the virus, we find that participants surveyed before and after the announcement did not differ in their risk perception regardless of political orientation. In Study 2, measuring belief that the virus is a hoax, we find that among those on the far right of the political spectrum, hoax belief was lower for those surveyed after the announcement, suggesting that Trump's hospitalization may have affected the beliefs of those most receptive to the President's earlier suggestions that the virus might be a hoax.

Early Administration of Anti-SARS-CoV-2 Monoclonal Antibodies Prevents Severe COVID-19 in Kidney Transplant Patients.

Introduction: Kidney transplant recipients (KTRs) are prone to develop severe COVID-19 and are less well protected by vaccine than immunocompetent subjects. Thus, the use of neutralizing anti-SARS-CoV-2 monoclonal antibody (MoAb) to confer a passive immunity appears attractive in KTRs. Methods: We performed a French nationwide study to compare COVID-19-related hospitalization, 30-day admission to intensive care unit (ICU), and 30-day death between KTRs who received an early infusion of MoAb (MoAb group) and KTRs who did not (control group). Controls were identified from the COVID-SFT registry (NCT04360707) using a propensity score matching with the following covariates: age, sex, delay between transplantation and infection, induction and maintenance immunosuppressive therapy, initial symptoms, and comorbidities. Results: A total of 80 KTRs received MoAb between February 2021 and June 2021. They were matched to 155 controls. COVID-19-related hospitalization, 30-day admission to ICU, and 30-day death were less frequently observed in the MoAb group (35.0% vs. 49.7%, P = 0.032; 2.5% vs. 15.5%, P = 0.002; 1.25% vs. 11.6%, P = 0.005, respectively). No patient required mechanical ventilation in the MoAb group. The number of patients to treat to prevent 1 death was 9.7. Conclusion: The early use of MoAb in KTRs with a mild form of COVID-19 largely improved outcomes in KTRs.

Can supplemental protein to low-protein containing meals superimpose on resistance-training muscle adaptations in older adults? A randomized clinical trial.

PURPOSE: To evaluate the effects of supplementing protein to the low-protein containing meals on selected parameters of muscle mass, strength, and functional capacity in older individuals undergoing resistance training. METHODS: Thirty-one male and female older individuals (60 to 80 years) were randomized into either a whey protein/WP (n = 15, 20 g at breakfast + 20 g at dinner) or placebo-maltodextrin/PL (n = 16, 20 g at breakfast + 20 g at dinner) group. Both groups underwent a supervised, progressive resistance training (2×/week) program for 12 weeks. Maximal isometric voluntary contraction (MIVC) of knee extensors, muscle thickness (MT) of knee extensors and elbow flexors, rectus femoris muscle quality (MQ), body composition (as measured by DXA) and functional capacity [as measured by 30-s sit-to-stand (30ss) and timed-up-and-go tests (TUG)] were evaluated at baseline and after the 12-week intervention. RESULTS: Knee extensor MIVC (WP ∆ = 11.9 ± 11.4% and PL ∆ = 12.9 ± 9.9%) was significantly increased over time, with no between-group differences (all p < 0.05 for main effect of time). Upper- and lower-limb MT were significantly increased over time, with no effect of supplementation (WP: ∆ = 7.0 ± 7.3%, PL: ∆ = 9.5 ± 10.3%; and WP: ∆ = 4.5 ± 5.8%, PL: ∆ = 14.7 ± 28.9%, respectively; all p = 0.001 for main effect of time, respectively). Total and upper-limb lean mass were significantly increased, irrespective of the dietary intervention (WP: ∆ = 0.2 ± 6.3%, PL: ∆ = 1.8 ± 2.9%; and WP: ∆ = 0.10 ± 0.03%, PL: ∆ = 0.15 ± 0.02%, respectively; all p < 0.05 for main effect of time). Main effects of time (all p < 0.05) were also found for 30SS and TUG (fast and usual speeds) (WP: ∆ = 18.2 ± 34.4%, PL: ∆ = 10.4 ± 16.9%; WP: ∆ = 5.4 ± 6.7%, PL: ∆ = 0.7 ± 6.0% and WP: ∆ = 3.3 ± 6.1%, PL: ∆ = 2.3 ± 5.2%, respectively). CONCLUSION: Supplementing additional whey protein to the lowest-protein containing meals (i.e., ~20 g at breakfast and ~20 g at dinner, daily) did not further augment resistance training-induced neuromuscular adaptations (i.e. muscle strength and mass) in healthy older individuals.

Transparent communication of evidence does not undermine public trust in evidence.

Does clear and transparent communication of risks, benefits, and uncertainties increase or undermine public trust in scientific information that people use to guide their decision-making? We examined the impact of reframing messages written in traditional persuasive style to align instead with recent "evidence communication" principles, aiming to inform decision-making: communicating a balance of risks and benefits, disclosing uncertainties and evidence quality, and prebunking misperceptions. In two pre-registered experiments, UK participants read either a persuasive message or a balanced and informative message adhering to evidence communication recommendations about COVID-19 vaccines (Study 1) or nuclear power plants (Study 2). We find that balanced messages are either perceived as trustworthy as persuasive messages (Study 1), or more so (Study 2). However, we note a moderating role of prior beliefs such that balanced messages were consistently perceived as more trustworthy among those with negative or neutral prior beliefs about the message content. We furthermore note that participants who had read the persuasive message on nuclear power plants voiced significantly stronger support for nuclear power than those who had read the balanced message, despite rating the information as less trustworthy. There was no difference in vaccination intentions between groups reading the different vaccine messages.

Effects of omega-3 supplementation on muscle damage after resistance exercise in young women: a randomized placebo-controlled trial.

BACKGROUND: Omega-3 is a nutritional strategie that have been used to recover muscles from exercise-induced muscle damage in a preventive perspective. AIM: To verify whether omega-3 (ω-3) supplementation after a session of resistance exercise facilitates muscle recovery in women undergoing a balanced diet. METHODS: This clinical trial was registered under the number NCT02839525. Thirty healthy women (22.2 ± 3.3 years) participated in this double-blinded, placebo-controlled trial. They were randomly distributed into ω-3 (n=15) and placebo (n=15) groups. They ingested ω-3 fish oil (3200 mg/day) or placebo (olive oil) at the dinner after the exercise bout (10 sets of 10 unilateral eccentric contractions in a knee extension chair), as well as at lunch for the three subsequent days. In addition, both groups followed a balanced diet along the four days. Muscle soreness and maximal isometric and isokinetic voluntary contractions were assessed immediately before, and 24, 48, and 72 hours after the resistance exercise. MAIN FINDINGS: There was no significant group-time interaction for any outcome. Participants presented increased levels of muscle soreness and reduced muscle strength capacity along the three days after exercise. There was no difference between placebo and ω-3 groups. CONCLUSION: Supplementation of ω-3 fish oil for three days after resistance exercise provided no additional benefits compared to placebo supplementation on recovery of healthy young women following a balanced diet.

The effects of quality of evidence communication on perception of public health information about COVID-19: Two randomised controlled trials.

BACKGROUND: The quality of evidence about the effectiveness of non-pharmaceutical health interventions is often low, but little is known about the effects of communicating indications of evidence quality to the public. METHODS: In two blinded, randomised, controlled, online experiments, US participants (total n = 2140) were shown one of several versions of an infographic illustrating the effectiveness of eye protection in reducing COVID-19 transmission. Their trust in the information, understanding, feelings of effectiveness of eye protection, and the likelihood of them adopting it were measured. FINDINGS: Compared to those given no quality cues, participants who were told the quality of the evidence on eye protection was 'low', rated the evidence less trustworthy (p = .001, d = 0.25), and rated it as subjectively less effective (p = .018, d = 0.19). The same effects emerged compared to those who were told the quality of the evidence was 'high', and in one of the two studies, those shown 'low' quality of evidence said they were less likely to use eye protection (p = .005, d = 0.18). Participants who were told the quality of the evidence was 'high' showed no statistically significant differences on these measures compared to those given no information about evidence quality. CONCLUSIONS: Without quality of evidence cues, participants responded to the evidence about the public health intervention as if it was high quality and this affected their subjective perceptions of its efficacy and trust in the provided information. This raises the ethical dilemma of weighing the importance of transparently stating when the evidence base is actually low quality against evidence that providing such information can decrease trust, perception of intervention efficacy, and likelihood of adopting it.

Correlates of intended COVID-19 vaccine acceptance across time and countries: results from a series of cross-sectional surveys.

OBJECTIVE: Describe demographical, social and psychological correlates of willingness to receive a COVID-19 vaccine. SETTING: Series of online surveys undertaken between March and October 2020. PARTICIPANTS: A total of 25 separate national samples (matched to country population by age and sex) in 12 different countries were recruited through online panel providers (n=25 334). PRIMARY OUTCOME MEASURES: Reported willingness to receive a COVID-19 vaccination. RESULTS: Reported willingness to receive a vaccine varied widely across samples, ranging from 63% to 88%. Multivariate logistic regression analyses reveal sex (female OR=0.59, 95% CI 0.55 to 0.64), trust in medical and scientific experts (OR=1.28, 95% CI 1.22 to 1.34) and worry about the COVID-19 virus (OR=1.47, 95% CI 1.41 to 1.53) as the strongest correlates of stated vaccine acceptance considering pooled data and the most consistent correlates across countries. In a subset of UK samples, we show that these effects are robust after controlling for attitudes towards vaccination in general. CONCLUSIONS: Our results indicate that the burden of trust largely rests on the shoulders of the scientific and medical community, with implications for how future COVID-19 vaccination information should be communicated to maximise uptake.

Teaching clinical practical and communication skills of the clinical skills lab of the University of Veterinary Medicine Hannover, Foundation, Germany during the COVID-19 pandemic.

Objective: The aim of the project is to teach clinical practical and communication skills in the Clinical Skills Lab (CSL) of the University of Veterinary Medicine Hannover, Foundation (TiHo) during the COVID-19 pandemic. Methodology: As a measure to limit potential SARS-CoV2 infections, the CSL learning stations were digitised and made available on the Moodle learning platform of the TiHo. Online quiz stations were also developed, as well as improvisations that allowed students to practise practical skills at home using everyday materials. Courses for Practical Year (PY) students were digitised and again combined with classroom exercises throughout the year. The teaching formats could be evaluated by the students by means of a questionnaire using a Likert scale (1=agree; 4=disagree). Results: A total of 24.92% of students (n=1272) completed the learning stations with improvisations. The quiz stations were completed with a percentage of 75.08%. Students indicated that the improvisations were easily implementable from home (M=1.33) and assisted in learning the practical skills in question (M=1.89). The quiz stations were considered helpful (M=1.40) and complementary to previous CSL offers (M=1.13). The PY students found the amount of teaching materials adequate (M=1.76) and described communication with the lecturers as problem-free (compulsory electives=1.24). Conclusions: Digital teaching is suitable as a supplement to existing face-to-face courses at the CSL, but cannot replace on-site training under the guidance of trained personnel. The CSL will continue to strive for a combination of online and face-to-face courses for some learning stations in the future.

Communicating personalized risks from COVID-19: guidelines from an empirical study.

As increasing amounts of data accumulate on the effects of the novel coronavirus SARS-CoV-2 and the risk factors that lead to poor outcomes, it is possible to produce personalized estimates of the risks faced by groups of people with different characteristics. The challenge of how to communicate these then becomes apparent. Based on empirical work (total n = 5520, UK) supported by in-person interviews with the public and physicians, we make recommendations on the presentation of such information. These include: using predominantly percentages when communicating the absolute risk, but also providing, for balance, a format which conveys a contrasting (higher) perception of risk (expected frequency out of 10 000); using a visual linear scale cut at an appropriate point to illustrate the maximum risk, explained through an illustrative 'persona' who might face that highest level of risk; and providing context to the absolute risk through presenting a range of other 'personas' illustrating people who would face risks of a wide range of different levels. These 'personas' should have their major risk factors (age, existing health conditions) described. By contrast, giving people absolute likelihoods of other risks they face in an attempt to add context was considered less helpful. We note that observed effect sizes generally were small. However, even small effects are meaningful and relevant when scaled up to population levels.

How do the UK public interpret COVID-19 test results? Comparing the impact of official information about results and reliability used in the UK, USA and New Zealand: a randomised controlled trial.

OBJECTIVES: To assess the effects of different official information on public interpretation of a personal COVID-19 PCR test result. DESIGN: A 5×2 factorial, randomised, between-subjects experiment, comparing four wordings of information about the test result and a control arm of no additional information; for both positive and negative test results. SETTING: Online experiment using recruitment platform Respondi. PARTICIPANTS: UK participants (n=1744, after a pilot of n=1657) quota-sampled to be proportional to the UK national population on age and sex. INTERVENTIONS: Participants were given a hypothetical COVID-19 PCR test result for 'John' who was presented as having a 50% chance of having COVID-19 based on symptoms alone. Participants were randomised to receive either a positive or negative result for 'John', then randomised again to receive either no more information, or text information on the interpretation of COVID-19 test results copied in September 2020 from the public websites of the UK's National Health Service, the USA's Centers for Disease Control, New Zealand's Ministry of Health or a modified version of the UK's wording. Information identifying the source of the wording was removed. MAIN OUTCOME MEASURES: Participants were asked 'What is your best guess as to the percent chance that John actually had COVID-19 at the time of his test, given his result?'; questions about their feelings of trustworthiness in the result, their perceptions of the quality of the underlying evidence and what action they felt 'John' should take in the light of his result. RESULTS: Of those presented with a positive COVID-19 test result for 'John', the mean estimate of the probability that he had the virus was 73% (71.5%-74.5%); for those presented with a negative result, 38% (36.7%-40.0%). There was no main effect of information (wording) on these means. However, those participants given the official information from the UK website, which did not mention the possibility of false negatives or false positives, were more likely to give a categorical (100% or 0%) answer (UK: 68/343, 19.8% (15.9%-24.4%); control group: 42/356, 11.8% (8.8%-15.6%)); the reverse was true for those viewing the New Zealand (NZ) wording, which highlighted the uncertainties most explicitly (20/345: 5.8% (3.7%-8.8%)). Aggregated across test result (positive/negative), there was a main effect of wording (p<0.001) on beliefs about how 'John' should behave, with those seeing the NZ wording marginally more likely to agree that 'John' should continue to self-isolate than those viewing the control or the UK wording. The proportion of participants who felt that a symptomatic individual who tests negative definitely should not self-isolate was highest among those viewing the UK wording (31/178, 17.4% (12.5%-23.7%)), and lowest among those viewing the NZ wording (6/159, 3.8% (1.6%-8.2%)). Although the NZ wording was rated harder to understand, participants reacted to the uncertainties given in the text in the expected direction: there was a small main effect of wording on trust in the result (p=0.048), with people perceiving the test result as marginally less trustworthy after having read the NZ wording compared with the UK wording. Positive results were generally viewed as more trustworthy and as having higher quality of evidence than negative results (both p<0.001). CONCLUSIONS: The public's default assessment of the face value of both the positive and negative test results (control group) indicate an awareness that test results are not perfectly accurate. Compared with other messaging tested, participants shown the UK's 2020 wording about the interpretation of the test results appeared to interpret the results as more definitive than is warranted. Wording that acknowledges uncertainty can help people to have a more nuanced and realistic understanding of what a COVID-19 test result means, which supports decision making and behavioural response. PREREGISTRATION AND DATA REPOSITORY: Preregistration of pilot at osf.io/8n62f, preregistration of main experiment at osf.io/7rcj4, data and code available online (osf.io/pvhba).

RNA helicase-mediated regulation of snoRNP dynamics on pre-ribosomes and rRNA 2'-O-methylation.

RNA helicases play important roles in diverse aspects of RNA metabolism through their functions in remodelling ribonucleoprotein complexes (RNPs), such as pre-ribosomes. Here, we show that the DEAD box helicase Dbp3 is required for efficient processing of the U18 and U24 intron-encoded snoRNAs and 2'-O-methylation of various sites within the 25S ribosomal RNA (rRNA) sequence. Furthermore, numerous box C/D snoRNPs accumulate on pre-ribosomes in the absence of Dbp3. Many snoRNAs guiding Dbp3-dependent rRNA modifications have overlapping pre-rRNA basepairing sites and therefore form mutually exclusive interactions with pre-ribosomes. Analysis of the distribution of these snoRNAs between pre-ribosome-associated and 'free' pools demonstrated that many are almost exclusively associated with pre-ribosomal complexes. Our data suggest that retention of such snoRNPs on pre-ribosomes when Dbp3 is lacking may impede rRNA 2'-O-methylation by reducing the recycling efficiency of snoRNPs and by inhibiting snoRNP access to proximal target sites. The observation of substoichiometric rRNA modification at adjacent sites suggests that the snoRNPs guiding such modifications likely interact stochastically rather than hierarchically with their pre-rRNA target sites. Together, our data provide new insights into the dynamics of snoRNPs on pre-ribosomal complexes and the remodelling events occurring during the early stages of ribosome assembly.