A longitudinal person-centered investigation of the multidimensional nature of employees' perceptions of challenge and hindrance demands at work.

BACKGROUND AND OBJECTIVES: This research relies on a combination of variable- and person-centered approaches to help improve our understanding of the dimensionality of job demands by jointly considering employees' global levels of job demands, exposure and their specific levels of exposure to challenge and hindrance demands. DESIGN AND METHODS: We relied on a sample of 442 workers who completed a questionnaire twice over three months. Our analyses sought to identify the nature of the job demands profiles experienced by these workers, to document the stability of these profiles over time, and to assess their associations with theoretically-relevant outcomes (i.e., work engagement, job boredom, problem-solving pondering, work-related rumination, proactive health behaviors, and sleep quality and quantity). Furthermore, we examined whether these profiles and associations differed as a function of working remotely or onsite. RESULTS: Five profiles were identified and found to be highly stable over time: Globally Exposed, Not Exposed, Not Exposed but Challenged, Exposed but Not Challenged, and Mixed. These profiles shared clear associations with all outcomes, with the most adaptive outcomes associated with the Exposed but Not Challenged profile, whereas the most detrimental ones were observed in the Mixed profile. However, none of these results differed across employees working onsite and those working remotely. CONCLUSIONS: These findings have theoretical and practical implications regarding the effects of work characteristics on employees' functioning.

Development of a revised version of the transdiagnostic skills scale (T2S-R).

Introduction: The transdiagnostic approach has been shown to offer promising prospects in psychopathology, based on the observation that common factors may be involved in different psychiatric disorders. The transdiagnostic skills scale (T2S) was developed recently to assess the skills that are disrupted in these disorders. However, studies have shown that the T2S has lower predictive power for externalizing than internalizing disorders. This may be due to the fact that the skills assessed do not include the control of urges and cravings. The aims of the current study are thus to develop a revised version of the T2S (T2S-R) integrating this dimension, and to assess its factor structure and invariance across employment status (workers vs. students) and the level of psychopathology. Method: We recruited 1,298 French participants online through social media. They completed the revised version of the T2S and the symptomatic transdiagnostic test (S2T), which evaluates 11 clusters of psychiatric symptoms. We assessed the factor structure, internal consistency, invariance, and predictive validity of the revised T2S. Results: We found a good fit for a bifactor exploratory structural equation modeling (B-ESEM) approach including a global skills factor and seven specific factors. The results also indicate that the new dimension (i.e., control of urges and cravings) has good predictive value, especially for externalizing problems. We also found total invariance of the scale across employment status and partial invariance across the level of psychopathology. Conclusion: The revised version of the T2S-R has good psychometric properties. It predicts better externalizing problems than the original version. However, the scale remains more correlated with internalizing than externalizing problems. We discuss the implications of the results on the transdiagnostic conceptualization and the interest of using a mixed approach combining transdiagnostic and diagnostic analyses.

A longitudinal investigation of structural empowerment profiles among healthcare employees.

PURPOSE: Research on structural empowerment has typically adopted a variable-centered perspective, which is not ideal to study the combined effects of structural empowerment components. This person-centered investigation aims to enhance our knowledge about the configurations, or profiles, of healthcare employees' perceptions of the structural empowerment dimensions present in their workplace (opportunity, information, support, and resources). Furthermore, this study considers the replicability and stability of these profiles over a period of 2 years, and their outcomes (perceived quality of care, and positive and negative affect). DESIGN: Participants completed the same self-reported questionnaires twice, 2 years apart. METHODS: A sample of 633 healthcare employees (including a majority of nurses and nursing assistants) participated. Latent transition analyses were performed. RESULTS: Five profiles were identified: Low Empowerment, High Information, Normative, Moderately High Empowerment, and High Empowerment. Membership into the Normative and Moderately High Empowerment profiles demonstrated a high level of stability over time (79.1% to 83.2%). Membership in the other profiles was either moderately stable (43.5% for the High Empowerment profile) or relatively unstable (19.7% to 20.4% for the Low Empowerment and High Information profiles) over time. More desirable outcomes (i.e., higher positive affect and quality of care, and lower negative affect) were observed in the High Empowerment profile. CONCLUSIONS: These results highlight the benefits of high structural empowerment, in line with prior studies suggesting that structural empowerment can act as a strong organizational resource capable of enhancing the functioning of healthcare professionals. These findings additionally demonstrate that profiles characterized by the highest or lowest levels of structural empowerment were less stable over time than those characterized by more moderate levels. CLINICAL RELEVANCE: From an intervention perspective, organizations and managers should pay special attention to employees perceiving low levels of structural empowerment, as they experience the worst outcomes. In addition, they should try to maintain high levels of structural empowerment within the High Empowerment profile, as this profile is associated with the most desirable consequences. Such attention should be fruitful, considering the instability of the High Empowerment and Low Empowerment profiles over time. REGISTRATION: NCT04010773 on ClinicalTrials.gov (4 July, 2019).

Viral Entry Inhibitors Protect against SARS-CoV-2-Induced Neurite Shortening in Differentiated SH-SY5Y Cells.

The utility of human neuroblastoma cell lines as in vitro model to study neuro-invasiveness and neuro-virulence of SARS-CoV-2 has been demonstrated by our laboratory and others. The aim of this report is to further characterize the associated cellular responses caused by a pre-alpha SARS-CoV-2 strain on differentiated SH-SY5Y and to prevent its cytopathic effect by using a set of entry inhibitors. The susceptibility of SH-SY5Y to SARS-CoV-2 was confirmed at high multiplicity-of-infection, without viral replication or release. Infection caused a reduction in the length of neuritic processes, occurrence of plasma membrane blebs, cell clustering, and changes in lipid droplets electron density. No changes in the expression of cytoskeletal proteins, such as tubulins or tau, could explain neurite shortening. To counteract the toxic effect on neurites, entry inhibitors targeting TMPRSS2, ACE2, NRP1 receptors, and Spike RBD were co-incubated with the viral inoculum. The neurite shortening could be prevented by the highest concentration of camostat mesylate, anti-RBD antibody, and NRP1 inhibitor, but not by soluble ACE2. According to the degree of entry inhibition, the average amount of intracellular viral RNA was negatively correlated to neurite length. This study demonstrated that targeting specific SARS-CoV-2 host receptors could reverse its neurocytopathic effect on SH-SY5Y.

Psychological need satisfaction across work and personal life: an empirical test of a comprehensive typology.

Introduction: A comprehensive typology of the satisfaction of psychological needs at work and in personal life was developed and tested. The typology proposes five scenarios (Enriched, Middling, Impoverished, Work-Fulfilled, and Personal Life-Fulfilled) accounting for various profiles of employees showing distinct configurations of global and specific levels of need satisfaction at work and in personal life. Methods: The scenarios were tested in a sample of 1,024 employees. Results: Using latent profile analysis, five profiles were identified that were consistent with four or the five scenarios, either aligned (Globally Satisfied, Globally Unsatisfied) or misaligned (Globally Satisfied at Work with High Relatedness, Globally Satisfied in Personal Life with High Autonomy, and Globally Satisfied in Personal Life with Low Autonomy) across domains. No profile corresponding to the Middling scenario was observed. Discussion: The results indicate that perceived job and individual characteristics predicted membership in distinct profiles. More importantly, unlike the profile Globally Unsatisfied, the profile Globally Satisfied contributed substantially to higher well-being (vitality and lower psychological distress), and to more favorable job attitudes (job satisfaction and lower turnover intentions) and behaviors (self-rated job performance and lower absenteeism, presenteeism, and work injuries). Furthermore, two of the misaligned profiles were also substantially associated with highly desirable outcome levels.

Specific DMPK-promoter targeting by CRISPRi reverses myotonic dystrophy type 1-associated defects in patient muscle cells.

Myotonic dystrophy type 1 (DM1) is a neuromuscular disease that originates from an expansion of CTG microsatellites in the 3' untranslated region of the DMPK gene, thus leading to the expression of transcripts containing expanded CUG repeats (CUGexp). The pathophysiology is explained by a toxic RNA gain of function where CUGexp RNAs form nuclear aggregates that sequester and alter the function of MBNL splicing factors, triggering splicing misregulation linked to the DM1 symptoms. There is currently no cure for DM1, and most therapeutic strategies aim at eliminating CUGexp-DMPK transcripts. Here, we investigate a DMPK-promoter silencing strategy using CRISPR interference as a new alternative approach. Different sgRNAs targeting the DMPK promoter are evaluated in DM1 patient muscle cells. The most effective guides allowed us to reduce the level of DMPK transcripts and CUGexp-RNA aggregates up to 80%. The CUGexp-DMPK repression corrects the overall transcriptome, including spliceopathy, and reverses a physiological parameter in DM1 muscle cells. Its action is specific and restricted to the DMPK gene, as confirmed by genome-wide expression analysis. Altogether, our findings highlight DMPK-promoter silencing by CRISPRi as a promising therapeutic approach for DM1.

The APOBEC3B cytidine deaminase is an adenovirus restriction factor.

Human adenoviruses (HAdVs) are a large family of DNA viruses counting more than a hundred strains divided into seven species (A to G). HAdVs induce respiratory tract infections, gastroenteritis and conjunctivitis. APOBEC3B is a cytidine deaminase that restricts several DNA viruses. APOBEC3B is also implicated in numerous cancers where it is responsible for the introduction of clustered mutations into the cellular genome. In this study, we demonstrate that APOBEC3B is an adenovirus restriction factor acting through a deaminase-dependent mechanism. APOBEC3B introduces C-to-T clustered mutations into the adenovirus genome. APOBEC3B reduces the propagation of adenoviruses by limiting viral genome replication, progression to late phase, and production of infectious virions. APOBEC3B restriction efficiency varies between adenoviral strains, the A12 strain being more sensitive to APOBEC3B than the B3 or C2 strains. In A12-infected cells, APOBEC3B clusters in the viral replication centers. Importantly, we show that adenovirus infection leads to a reduction of the quantity and/or enzymatic activity of the APOBEC3B protein depending on the strains. The A12 strain seems less able to resist APOBEC3B than the B3 or C2 strains, a characteristic which could explain the strong depletion of the APOBEC3-targeted motifs in the A12 genome. These findings suggest that adenoviruses evolved different mechanisms to antagonize APOBEC3B. Elucidating these mechanisms could benefit the design of cancer treatments. This study also identifies adenoviruses as triggers of the APOBEC3B-mediated innate response. The involvement of certain adenoviral strains in the genesis of the APOBEC3 mutational signature observed in tumors deserves further study.

Human papillomavirus E6/E7 oncoproteins promote radiotherapy-mediated tumor suppression by globally hijacking host DNA damage repair.

Rationale: Whatever the mucosa primary infected, HPV-positive cancers are traditionally associated with a favorable outcome, attributable to a high sensitivity to radiation therapy. However, the direct impact of viral E6/E7 oncoproteins on the intrinsic cellular radiosensitivity (and, globally, on host DNA repair) remains mostly speculative. Methods: Using several isogenic cell models expressing HPV16 E6 and/or E7, the effect of viral oncoproteins on global DNA damage response was first investigated by in vitro/in vivo approaches. The binary interactome of each individual HPV oncoprotein with factors involved in the various host DNA damage/repair mechanisms was then precisely mapped by Gaussia princeps luciferase complementation assay (and validated by co-immunoprecipitation). The stability/half-life of protein targets for HPV E6 and/or E7 as well as their subcellular localizations were determined. At last, the host genome integrity following E6/E7 expression and the synergy between radiotherapy and compounds targeting DNA repair were analyzed. Results: We first showed that the sole expression of one viral oncoprotein from HPV16 was able to significantly increase the sensitivity to irradiation of cells without affecting their basal viability parameters. In total, 10 novel targets (CHEK2, CLK2, CLK2/3, ERCC3, MNAT1, PER1, RMI1, RPA1, UVSSA and XRCC6) for E6 and 11 (ALKBH2, CHEK2, DNA2, DUT, ENDOV, ERCC3, PARP3, PMS1, PNKP, POLDIP2 and RBBP8) for E7 were identified. Importantly, not degraded following their interaction with E6 or E7, these proteins have been shown to be less linked to host DNA and to colocalize with HPV replication foci, denoting their crucial implication in viral life cycle. Finally, we found that E6/E7 oncoproteins globally jeopardize host genome integrity, increase the cellular sensitivity to DNA repair inhibitors and enhance their synergy with radiotherapy. Conclusion: Taken together, our findings provide a molecular insight into the direct hijacking of host DNA damage/repair responses by HPV oncoproteins, demonstrate the significant impact of this phenomenon on both intrinsic cellular radiosensitivity and host DNA integrity and suggest novel connected therapeutic vulnerabilities.

Impact of empowering leadership on emotional exhaustion: A controlled interventional study in a large French university hospital complex.

AIM: The aim of this study is to assess the effect of a systemic intervention on the evolution of empowering leadership and emotional exhaustion in a university hospital sub-centre compared to a control sub-centre, both being part of a large French university hospital complex. BACKGROUND: Empowering leadership is a promising strategy for developing hospital team engagement and performance. However, the bureaucratic functioning of large hospitals, characterized by a managerial culture of control and a stratified organization, can be a barrier to empowering leadership. METHODS: The intervention included empowering leadership training, direct field experimentation of empowering leadership and coaching, involving all the sub-centre hierarchical levels for 12 months. Data were collected before and after the intervention. A total of 441 and 310 participants were, respectively, included in the intervention and control sub-centres. RESULTS: Empowering leadership was decreased, and emotional exhaustion was increased in the control sub-centre, while the scores remained stable in the intervention sub-centre. The increased emotional exhaustion in the control sub-centre could partially be explained by the change in empowering leadership. CONCLUSION: In a context of decreased empowering leadership and increased emotional exhaustion, the intervention had a protective effect. Implications for the design of future interventions were discussed. IMPLICATIONS FOR NURSING MANAGEMENT: This study unequivocally showed the benefit of transforming hospital management towards empowering leadership, to prevent increased emotional exhaustion. REGISTRATION NUMBER: This study is registered on ClinicalTrials.gov on 4 July 2019 (NCT04010773).

Benefits of psychological detachment from work in a digital era: How do job stressors and personal strategies interplay with individual vulnerabilities?

This study examined how individual strategies (boundary creation around information and communication technology; ICT) and job stressors (work-related extended availability) relate to psychological detachment, and how the latter associates with employees' behaviors (presenteeism) and attitudes (family life satisfaction). This research also explored the moderating role of performance-based self-esteem in these relationships. Questionnaire surveys were collected among 321 teachers in Sample 1 and 283 workers in Sample 2. Results from Sample 1 revealed that boundary creation surrounding ICT was positively linked to psychological detachment but only among employees with low performance-based self-esteem. Results from Sample 2 indicated that work-related extended availability negatively related to psychological detachment but only among employees with high performance-based self-esteem. In addition, psychological detachment was associated with lower levels of presenteeism (Samples 1 and 2) and higher levels of family-life satisfaction (Sample 2). More generally, these results confirm performance-based self-esteem to be a maladaptive individual characteristic, adding up to a negative cycle of stressors to decrease psychological detachment, in turn leading to maladaptive functioning.

Satellite magnetic data reveal interannual waves in Earth's core.

SignificanceThe physics responsible for most of the interannual geomagnetic field changes, continually recorded by satellites for 20 years, is a long-standing open issue. By analyzing magnetic data, we detect Magneto-Coriolis waves in the Earth's outer core that account for a significant part of this signal. We further propose theoretical advances in the physical characterization of these waves, enabling a deeper understanding of the dynamics behind the geomagnetic signal. It should allow one to better sketch the heterogeneous magnetic field deep within the core, shedding further light on the mechanisms that sustain the geodynamo. Our interpretation does not require the presence of a stratified layer at the top of the core, with potent consequences regarding the Earth's thermal history.

Bullying, supervisor support, relaxation, and personal and work outcomes: Testing a moderated mediation model.

AIM: To test a mediated moderation model in which bullying and supervisor support interact to predict nurses' personal and work outcomes with relaxation during off-job time mediating these effects. BACKGROUND: Bullying is a pervasive problem in the nursing profession. We integrate and extend past research addressing the question of how bullying and perceived supervisor support affect nurses' functioning. METHOD: Cross-sectional data were collected from a sample of 290 nurses who completed measures of bullying, perceived supervisor support, relaxation, need for recovery, sleeping problems, job satisfaction, emotional exhaustion and work performance. RESULTS: Results revealed that bullying was significantly linked to job satisfaction, sleeping problems, need for recovery and emotional exhaustion through relaxation, but only among nurses who perceived high levels of supervisor support. CONCLUSION: These results revealed that high supervisor support may be detrimental for nurses adding up to a negative cycle of stressors to maladaptive outcomes through lack of relaxation. IMPLICATIONS FOR NURSING MANAGEMENT: Health care organisations and managers should consider addressing work environment factors, such as bullying, in addition to supervisor support in their efforts to facilitate the positive effects of nurses' relaxation during non-work time.

Complementary variable- and person-centered approaches to the dimensionality of burnout among fire station workers.

This research relies on variable- and person-centered approaches to illustrate how each of these approaches may help to improve our understanding of the dimensionality of the burnout construct. Both studies (Study 1: N = 247 administrative and technical employees; Study 2: N = 654 firefighters), showed that employees' burnout ratings simultaneously reflected a global overarching construct co-existing with two specific dimensions (cynicism and emotional exhaustion), with a distinct factor reflecting reduced professional efficacy. In Study 1, perceived supervisor recognition and job satisfaction were associated with lower levels of global burnout levels. In Study 2, we examined the configurations, or profiles, taken by burnout dimensions (global burnout, specific cynicism, specific emotional exhaustion, and reduced professional efficacy), and documented associations between these profiles and four covariates (organizational, supervisor, and colleagues recognition as well as job satisfaction). Five profiles were identified using latent profile analyses: Very Low Burnout Risk, Mentally Distanced, Low Burnout Risk, High Burnout Risk, and Moderately High Burnout Risk. Employees' perceptions of supervisor and colleagues recognition were related to their likelihood of profile membership. Employees' job satisfaction levels also differed as a function of their profile.

Control of APOBEC3B induction and cccDNA decay by NF-κB and miR-138-5p.

BACKGROUND & AIMS: Immune-mediated induction of cytidine deaminase APOBEC3B (A3B) expression leads to HBV covalently closed circular DNA (cccDNA) decay. Here, we aimed to decipher the signalling pathway(s) and regulatory mechanism(s) involved in A3B induction and related HBV control. METHODS: Differentiated HepaRG cells (dHepaRG) knocked-down for NF-κB signalling components, transfected with siRNA or micro RNAs (miRNA), and primary human hepatocytes ± HBV or HBVΔX or HBV-RFP, were treated with lymphotoxin beta receptor (LTßR)-agonist (BS1). The biological outcomes were analysed by reverse transcriptase-qPCR, immunoblotting, luciferase activity, chromatin immune precipitation, electrophoretic mobility-shift assay, targeted-bisulfite-, miRNA-, RNA-, genome-sequencing, and mass-spectrometry. RESULTS: We found that canonical and non-canonical NF-κB signalling pathways are mandatory for A3B induction and anti-HBV effects. The degree of immune-mediated A3B production is independent of A3B promoter demethylation but is controlled post-transcriptionally by the miRNA 138-5p expression (hsa-miR-138-5p), promoting A3B mRNA decay. Hsa-miR-138-5p over-expression reduced A3B levels and its antiviral effects. Of note, established infection inhibited BS1-induced A3B expression through epigenetic modulation of A3B promoter. Twelve days of treatment with a LTßR-specific agonist BS1 is sufficient to reduce the cccDNA pool by 80% without inducing significant damages to a subset of cancer-related host genes. Interestingly, the A3B-mediated effect on HBV is independent of the transcriptional activity of cccDNA as well as on rcDNA synthesis. CONCLUSIONS: Altogether, A3B represents the only described enzyme to target both transcriptionally active and inactive cccDNA. Thus, inhibiting hsa-miR-138-5p expression should be considered in the combinatorial design of new therapies against HBV, especially in the context of immune-mediated A3B induction. LAY SUMMARY: Immune-mediated induction of cytidine deaminase APOBEC3B is transcriptionally regulated by NF-κB signalling and post-transcriptionally downregulated by hsa-miR-138-5p expression, leading to cccDNA decay. Timely controlled APOBEC3B-mediated cccDNA decay occurs independently of cccDNA transcriptional activity and without damage to a subset of cancer-related genes. Thus, APOBEC3B-mediated cccDNA decay could offer an efficient therapeutic alternative to target hepatitis B virus chronic infection.

Predicting nurses' occupational commitment and turnover intention: The role of autonomous motivation and supervisor and coworker behaviours.

AIM: To examine whether supportive supervisor (transformational leadership) and coworker (autonomy-supportive) behaviours predict occupational commitment and turnover intention over time through autonomous motivation. BACKGROUND: Nurse turnover is a serious issue in several countries, straining the efficiency of the healthcare system and compromising both the quality and accessibility of healthcare. METHOD: Longitudinal data were collected over 12 months from 387 French-Canadian registered nurses. Structural equation modeling was used to test the hypothesized model. RESULTS: The relationships between predictors at Time 1 (supervisor and coworker behaviours) and occupational commitment and turnover intention at Time 2 are mediated by autonomous motivation at Time 1. CONCLUSION: In times of global scarcity, the present findings provide insights into how the healthcare work environment acts on nurses' occupational turnover and commitment. IMPLICATIONS FOR NURSING MANAGEMENT: Healthcare organizations are advised to foster supportive work environments and promote autonomous motivation to sustain the nursing workforce.

The Participatory Approach: A Specific French Organizational Model at the Department Level to Serve the Quality of Work Life of Healthcare Providers and the Quality of Care in Pediatric Oncology.

BACKGROUND: Care providers 'psychological health at work is an important issue because it directly affects the quality of patient care. So far, few studies have studied the psychological health at work of care providers in paediatric oncology. The participatory approach (PA) is an innovative organizational model of department specific to France and previously associated with quality of work life (QWL) and job performance. The aim of the present study was to explore the relationships between the participatory approach, care providers' QWL and quality of care of children in pediatric oncology departments in France. METHODS: A multicentre survey was carried out in pediatric cancer units in France. Care providers completed a questionnaire assessing PA, QWL, consequences of QWL, and their perception of quality of care. The children or their parents completed a questionnaire assessing their perception of quality of care. RESULTS: Five hundred and ten healthcare professionals working in French pediatric oncology centres (more than 40% of the healthcare staff in paediatric oncology in France), 142 children and 298 parents responded to the survey. PA was associated with the care providers' QWL (ß = 0.274; p <0.001), work engagement (ß = 0.167; p<0.001), job satisfaction (ß = 0.166; p<0.001) and perception of quality of care (ß = 0.236; p<0.001). PA was also related to patients' perception of quality of care notably regarding quality of communication (ß = 0.161; p<0.001) and information (ß = 0.226; p<0.001). CONCLUSION: PA is an innovative organizational model that appears to play a role in all aspects of healthcare providers' QWL, and in the quality of care perceived by both care providers and patients.

Workaholism, presenteeism, work-family conflicts and personal and work outcomes: Testing a moderated mediation model.

AIMS AND OBJECTIVES: While research suggests that nurses who experience work-family conflicts (WFC) are less satisfied and perform less well, these negative outcomes may be more important for some nurses. This study proposes a mediated moderation model wherein the interaction between two individual characteristics, workaholism and presenteeism, relates to family life satisfaction and work performance with WFC mediating these relationships. BACKGROUND: Because a limited number of nursing studies have examined the potential outcomes of workaholism and presenteeism, we extend past research to address the question of how workaholism and presenteeism affect nurses' functioning. DESIGN: We used a cross-sectional questionnaire survey design to test our hypotheses. STROBE guidelines for cross-sectional research were followed in designing and reporting this study. METHODS: A total of 419 nurses completed measures of workaholism, presenteeism, WFC, family life satisfaction and work performance. RESULTS: Results revealed that the relationships between workaholism and outcomes (family life satisfaction and work performance) through WFC were stronger among nurses characterised by high levels of presenteeism. CONCLUSIONS: These results revealed that high presenteeism may exacerbate the negative relationships of workaholism to family life satisfaction and work performance through WFC. RELEVANCE TO CLINICAL PRACTICE: Healthcare organisations and managers should consider addressing work environment factors in their efforts to reduce the negative outcomes (e.g., low family satisfaction and work performance) of nurses' workaholism, presenteeism and WFC.

Infection of Bronchial Epithelial Cells by the Human Adenoviruses A12, B3, and C2 Differently Regulates the Innate Antiviral Effector APOBEC3B.

Human adenoviruses (HAdVs) are a large family of DNA viruses that include more than 100 genotypes divided into seven species (A to G) and induce respiratory tract infections, gastroenteritis, and conjunctivitis. Genetically modified adenoviruses are also used as vaccines, gene therapies, and anticancer treatments. The APOBEC3s are a family of cytidine deaminases that restrict viruses by introducing mutations in their genomes. Viruses developed different strategies to cope with the APOBEC3 selection pressure, but nothing is known on the interplay between the APOBEC3s and the HAdVs. In this study, we focused on three HAdV strains: the B3 and C2 strains, as they are very frequent, and the A12 strain, which is less common but is oncogenic in animal models. We demonstrated that the three HAdV strains induce a similar APOBEC3B upregulation at the transcriptional level. At the protein level, however, APOBEC3B is abundantly expressed during HAdV-A12 and -C2 infection and shows a nuclear distribution. On the contrary, APOBEC3B is barely detectable in HAdV-B3-infected cells. APOBEC3B deaminase activity is detected in total protein extracts upon HAdV-A12 and -C2 infection. Bioinformatic analysis demonstrates that the HAdV-A12 genome bears a stronger APOBEC3 evolutionary footprint than that of the HAdV-C2 and HAdV-B3 genomes. Our results show that HAdV infection triggers the transcriptional upregulation of the antiviral innate effector APOBEC3B. The discrepancies between the APOBEC3B mRNA and protein levels might reflect the ability of some HAdV strains to antagonize the APOBEC3B protein. These findings point toward an involvement of APOBEC3B in HAdV restriction and evolution. IMPORTANCE The APOBEC3 family of cytosine deaminases has important roles in antiviral innate immunity and cancer. Notably, APOBEC3A and APOBEC3B are actively upregulated by several DNA tumor viruses and contribute to transformation by introducing mutations in the cellular genome. Human adenoviruses (HAdVs) are a large family of DNA viruses that cause generally asymptomatic infections in immunocompetent adults. HAdVs encode several oncogenes, and some HAdV strains, like HAdV-A12, induce tumors in hamsters and mice. Here, we show that HAdV infection specifically promotes the expression of the APOBEC3B gene. We report that infection with the A12 strain induces a strong expression of an enzymatically active APOBEC3B protein in bronchial epithelial cells. We provide bioinformatic evidence that HAdVs' genomes and notably the A12 genome are under APOBEC3 selection pressure. Thus, APOBEC3B might contribute to adenoviral restriction, diversification, and oncogenic potential of particular strains.

Susceptibility of neuroblastoma and glioblastoma cell lines to SARS-CoV-2 infection.

Modelling cell infection in-a-dish can represent a useful tool to understand the susceptibility of different cell types towards severe acute respiratory coronavirus-2 (SARS-CoV-2) and to decipher its neurotropism. In this perspective, retinoic acid (RA)-differentiated neuroblastoma cell lines, SH-SY5Y and SK-N-BE(2) and glioblastoma cell lines, U-87 MG and U-373 MG, were infected with a SARS-CoV-2 strain, at various multiplicity-of-infection (MOI). We first demonstrated that the common entry genes - needed for invading epithelial cells - were expressed. RA-differentiation induced an upregulation of ace2 and tmprss2 gene expression while inducing downregulation of ctsb and ctsl. Using in situ hybridization and confocal analysis, SARS-CoV-2 gene S RNA was detected intracellularly at MOI 5.0, and localized in both soma and neuritic-like or glial-like processes. The infection was confirmed by quantification of viral gene E RNA and showed a dose-dependency, with few infected cells at MOI 0.1. After 24 h of infection, no cytopathic effect was observed in SH-SY5Y abilities to maintain neuritic processes or in U-373 MG for the uptake of glutamate. Unlike the permissive Vero E6 cells, no significant apoptosis death was detected following SARS-CoV-2 infection of neuroblastoma or glioblastoma cells. This study demonstrates the susceptibility of neuronal- and glial-like cell lines towards SARS-CoV-2 infection at high MOIs. Once inside the cells, the virus does not seem to rapidly replicate nor exert major cytopathic effect. Overall, our results strengthen the idea that SARS-CoV-2 has a tropism for nervous cells that express commonly described entry genes.

Assessing the neuroanatomy knowledge and spatial ability of radiotherapy technologist undergraduates using an interactive volumetric simulation tool-the RadioLOG project.

OBJECTIVE: To assess the use of a volumetric image display simulation tool (VDST) for the evaluation of applied radiological neuroanatomy knowledge and spatial understanding of radiotherapy technologist (RTT) undergraduates. METHODS: Ninety-two third-year RTT students from three French RTT schools took an examination using software that allows visualization of multiple volumetric image series. To serve as a reference, 77 first- and second-year undergraduates, as well as ten senior neuroradiologists, took the same examination. The test included 13 very-short-answer questions (VSAQ) and 21 exercises in which examinees positioned markers onto preloaded brain MR images from a healthy volunteer. The response time was limited. Each correct answer scored 100 points, with a maximum possible test score of 3,400 (VSAQ = 1,300; marker exercise = 2,100). Answers were marked automatically for the marker positioning exercise and semi-automatically for the VSAQs against prerecorded expected answers. RESULTS: Overall, the mean test score was 1,787 (150-3,300) and the standard deviation was 781. Scores were highly significantly different between all evaluated groups (p < 0.001). The interoperator reproducibility was 0.90. All the evaluated groups could be discriminated by VSAQ, marker, and overall total scores independently (p ≤ 0.0001 to 0.001). The test was able to discriminate between the three schools either by VSAQ scores (p < 0.001 to 0.02) or by overall total score (p < 0.001 to 0.05). CONCLUSION: This software is a high-quality evaluation tool for the assessment of radiological neuroanatomy knowledge and spatial understanding in RTT undergraduates. KEY POINTS: • This VDST allows volumetric image analysis of MR studies. • A high reliability test could be created with this tool. • Test scores were strongly associated with the examinee expertise level.