Latent profiles of emotion regulation among university students: links to repetitive negative thinking, internet addiction, and subjective wellbeing.

Recent years have seen a deterioration in the mental health of university students and notable surge in the need for psychological support. Due to its links to psychopathology and high-risk behaviors, difficulty in emotion regulation frequently serves as a transdiagnostic dimension. This cross-sectional study used a person-centered analytical approach (latent profile analysis; LPA) to identify groups of Portuguese university students with similar profiles of emotion regulation difficulties (N = 261; Mage = 22.5 ± 1.2 years; n = 213 female) and describe how these groups differ in their presentation of repetitive negative thinking, internet addiction, and subjective wellbeing. The analyses identified four latent profiles: 14.5% of students showed global dysregulation (the Low Emotion Regulation Profile), 23% were moderately dysregulated with elevated problems in goal-directed behavior (the Moderate Emotion Regulation Profile), 8% showed specific difficulties with low emotional awareness and clarity (the Low Insight Profile), and 54.4% showed adaptive emotion regulation (the High Emotion Regulation Profile). As anticipated, the Low Emotion Regulation Profile had the lowest subjective wellbeing and the highest prevalence of repetitive negative thinking and internet addiction. Students with a Low Insight Profile also showed low subjective wellbeing, but less repetitive negative thinking compared to the Low Emotion Regulation Profile. Our findings suggest that interventions aimed at improving health and wellbeing among university students should consider each student's unique set of emotion regulation difficulties, rather than focusing on particular strategies. Further research may help determine whether emotion regulation profiles can serve as predictive indicators of varying mental health trajectories and subjective wellbeing in university students.

Diversity, habitat endemicity and trophic ecology of the fauna of Loki's Castle vent field on the Arctic Mid-Ocean Ridge.

Loki's Castle Vent Field (LCVF, 2300 m) was discovered in 2008 and represents the first black-smoker vent field discovered on the Arctic Mid-Ocean Ridge (AMOR). However, a comprehensive faunal inventory of the LCVF has not yet been published, hindering the inclusion of the Arctic in biogeographic analyses of vent fauna. There is an urgent need to understand the diversity, spatial distribution and ecosystem function of the biological communities along the AMOR, which will inform environmental impact assesments of future deep-sea mining activities in the region. Therefore, our aim with this paper is to provide a comprehensive inventory of the fauna at LCVF and present a first insight into the food web of the vent community. The fauna of LCVF has a high degree of novelty, with five new species previously described and another ten new species awaiting formal description. Most of the new species from LCVF are either hydrothermal vent specialists or have been reported from other chemosynthesis-based ecosystems. The highest taxon richness is found in the diffuse venting areas and may be promoted by the biogenic habitat generated by the foundation species Sclerolinum contortum. The isotopic signatures of the vent community of LCVF show a clear influence of chemosynthetic primary production on the foodweb. Considering the novel and specialised fauna documented in this paper, hydrothermal vents on the AMOR should be regarded as vulnerable marine ecosystems and protective measures must therefore be implemented, especially considering the potential threat from resource exploration and exploitation activities in the near future.

Eating disorders in weight-related therapy (EDIT): Protocol for a systematic review with individual participant data meta-analysis of eating disorder risk in behavioural weight management.

The Eating Disorders In weight-related Therapy (EDIT) Collaboration brings together data from randomised controlled trials of behavioural weight management interventions to identify individual participant risk factors and intervention strategies that contribute to eating disorder risk. We present a protocol for a systematic review and individual participant data (IPD) meta-analysis which aims to identify participants at risk of developing eating disorders, or related symptoms, during or after weight management interventions conducted in adolescents or adults with overweight or obesity. We systematically searched four databases up to March 2022 and clinical trials registries to May 2022 to identify randomised controlled trials of weight management interventions conducted in adolescents or adults with overweight or obesity that measured eating disorder risk at pre- and post-intervention or follow-up. Authors from eligible trials have been invited to share their deidentified IPD. Two IPD meta-analyses will be conducted. The first IPD meta-analysis aims to examine participant level factors associated with a change in eating disorder scores during and following a weight management intervention. To do this we will examine baseline variables that predict change in eating disorder risk within intervention arms. The second IPD meta-analysis aims to assess whether there are participant level factors that predict whether participation in an intervention is more or less likely than no intervention to lead to a change in eating disorder risk. To do this, we will examine if there are differences in predictors of eating disorder risk between intervention and no-treatment control arms. The primary outcome will be a standardised mean difference in global eating disorder score from baseline to immediately post-intervention and at 6- and 12- months follow-up. Identifying participant level risk factors predicting eating disorder risk will inform screening and monitoring protocols to allow early identification and intervention for those at risk.

Carbonate compensation depth drives abyssal biogeography in the northeast Pacific.

Abyssal seafloor communities cover more than 60% of Earth's surface. Despite their great size, abyssal plains extend across modest environmental gradients compared to other marine ecosystems. However, little is known about the patterns and processes regulating biodiversity or potentially delimiting biogeographical boundaries at regional scales in the abyss. Improved macroecological understanding of remote abyssal environments is urgent as threats of widespread anthropogenic disturbance grow in the deep ocean. Here, we use a new, basin-scale dataset to show the existence of clear regional zonation in abyssal communities across the 5,000 km span of the Clarion-Clipperton Zone (northeast Pacific), an area targeted for deep-sea mining. We found two pronounced biogeographic provinces, deep and shallow-abyssal, separated by a transition zone between 4,300 and 4,800 m depth. Surprisingly, species richness was maintained across this boundary by phylum-level taxonomic replacements. These regional transitions are probably related to calcium carbonate saturation boundaries as taxa dependent on calcium carbonate structures, such as shelled molluscs, appear restricted to the shallower province. Our results suggest geochemical and climatic forcing on distributions of abyssal populations over large spatial scales and provide a potential paradigm for deep-sea macroecology, opening a new basis for regional-scale biodiversity research and conservation strategies in Earth's largest biome.

Loss of Control over Eating, Inhibitory Control, and Reward Sensitivity in Children and Adolescents: A Systematic Review.

OVERVIEW: In recent years, there has been increasing clinical and empirical interest in the concept of pediatric loss of control over eating, particularly about its link with the executive functions related to the concept of impulsivity, such as inhibitory control and reward sensitivity. However, there has yet to be a comprehensive literature synthesis about the associations between these variables. A comprehensive literature synthesis would help identify future research directions to advance the field in this area. Therefore, this systematic review aimed to synthesize evidence concerning the associations between loss of control over eating, inhibitory control, and reward sensitivity in children and adolescents. METHODS: The systematic review was conducted according to the guidelines proposed by PRISMA in Web of Science, Scopus, PubMed, and PsycINFO. The Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies was used to assess the risk of bias. RESULTS: Twelve studies met the selection criteria and were included in the final review. Overall, methodological heterogeneity, variability in assessment methods, and the age of participants make it difficult to draw general conclusions. Nevertheless, most studies with community samples of adolescents indicate that inhibitory control difficulties are linked to the concept of loss of control eating. The presence of obesity seems to be associated with inhibitory control difficulties, regardless of the presence of loss of control eating. Studies on reward sensitivity are scarcer. However, it has been suggested that higher reward sensitivity is related to loss of control eating behaviors in young people, particularly binge eating. CONCLUSIONS: The literature on the link between loss of control eating and trait-level facets of impulsivity (low inhibitory control and higher reward sensitivity) among young people remains limited, and more studies on children are needed. Findings from this review may make healthcare professionals more aware of the potential clinical importance of targeting the trait-level facets of impulsivity and help to inform existing and future weight-loss/maintenance interventions in childhood and adolescence.

Personalized medicine: Function of CFTR variant p.Arg334Trp is rescued by currently available CFTR modulators.

Most of the 2,100 CFTR gene variants reported to date are still unknown in terms of their disease liability in Cystic Fibrosis (CF) and their molecular and cellular mechanism that leads to CFTR dysfunction. Since some rare variants may respond to currently approved modulators, characterizing their defect and response to these drugs is essential for effective treatment of people with CF (pwCF) not eligible for the current treatment. Here, we assessed how the rare variant, p.Arg334Trp, impacts on CFTR traffic and function and its response to existing CFTR modulators. To this end, we performed the forskolin-induced swelling (FIS) assay on intestinal organoids from 10 pwCF bearing the p.Arg334Trp variant in one or both alleles of the CFTR gene. In parallel, a novel p.Arg334Trp-CFTR expressing CFBE cell line was generated to characterize the variant individually. Results show that p.Arg334Trp-CFTR does not significantly affect the plasma membrane traffic of CFTR and evidences residual CFTR function. This CFTR variant is rescued by currently available CFTR modulators independently of the variant in the second allele. The study, predicting clinical benefit for CFTR modulators in pwCF with at least one p.Arg334Trp variant, demonstrates the high potential of personalized medicine through theranostics to extend the label of approved drugs for pwCF carrying rare CFTR variants. We recommend that this personalized approach should be considered for drug reimbursement policies by health insurance systems/national health services.

Rescue of Rare CFTR Trafficking Mutants Highlights a Structural Location-Dependent Pattern for Correction.

Cystic Fibrosis (CF) is a genetic disease caused by mutations in the gene encoding the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel. Currently, more than 2100 variants have been identified in the gene, with a large number being very rare. The approval of modulators that act on mutant CFTR protein, correcting its molecular defect and thus alleviating the burden of the disease, revolutionized the field of CF. However, these drugs do not apply to all patients with CF, especially those with rare mutations-for which there is a lack of knowledge on the molecular mechanisms of the disease and the response to modulators. In this work, we evaluated the impact of several rare putative class II mutations on the expression, processing, and response of CFTR to modulators. Novel cell models consisting of bronchial epithelial cell lines expressing CFTR with 14 rare variants were created. The variants studied are localized at Transmembrane Domain 1 (TMD1) or very close to the signature motif of Nucleotide Binding Domain 1 (NBD1). Our data show that all mutations analyzed significantly decrease CFTR processing and while TMD1 mutations respond to modulators, those localized in NBD1 do not. Molecular modeling calculations confirm that the mutations in NBD1 induce greater destabilization of CFTR structure than those in TMD1. Furthermore, the structural proximity of TMD1 mutants to the reported binding site of CFTR modulators such as VX-809 and VX-661, make them more efficient in stabilizing the CFTR mutants analyzed. Overall, our data suggest a pattern for mutation location and impact in response to modulators that correlates with the global effect of the mutations on CFTR structure.

Volcanically hosted venting with indications of ultramafic influence at Aurora hydrothermal field on Gakkel Ridge.

The Aurora hydrothermal system, Arctic Ocean, hosts active submarine venting within an extensive field of relict mineral deposits. Here we show the site is associated with a neovolcanic mound located within the Gakkel Ridge rift-valley floor, but deep-tow camera and sidescan surveys reveal the site to be ≥100 m across-unusually large for a volcanically hosted vent on a slow-spreading ridge and more comparable to tectonically hosted systems that require large time-integrated heat-fluxes to form. The hydrothermal plume emanating from Aurora exhibits much higher dissolved CH4/Mn values than typical basalt-hosted hydrothermal systems and, instead, closely resembles those of high-temperature ultramafic-influenced vents at slow-spreading ridges. We hypothesize that deep-penetrating fluid circulation may have sustained the prolonged venting evident at the Aurora hydrothermal field with a hydrothermal convection cell that can access ultramafic lithologies underlying anomalously thin ocean crust at this ultraslow spreading ridge setting. Our findings have implications for ultra-slow ridge cooling, global marine mineral distributions, and the diversity of geologic settings that can host abiotic organic synthesis - pertinent to the search for life beyond Earth.

Impact of returning scientific cruises and prolonged on-site presence on litter abundance at the deep-sea nodule fields in the Peru Basin.

Marine litter can be found along coasts, continental shelves and slopes, down into the abyss. The absence of light, low temperatures and low energy regimes characterising the deeper habitats ensure the persistence of litter over time. Therefore, manmade items within the deep sea will likely accumulate to increasing quantities. Here we report the litter abundance encountered at the Pacific abyssal nodule fields from the Peru Basin at 4150 m depth. An average density of 2.67 litter items/ha was observed. Litter composed of plastic was the most abundant followed by metal and glass. At least 58 % of the items observed could be linked to the research expeditions conducted in the area and appeared to be mostly accidental disposals from ships. The data gathered was used to address temporal trends in litter abundance as well as the impact of human on-site presence and return cruises in the context of future deep-sea mining efforts.

Ribosome impairment regulates intestinal stem cell identity via ZAKɑ activation.

The small intestine is a rapidly proliferating organ that is maintained by a small population of Lgr5-expressing intestinal stem cells (ISCs). However, several Lgr5-negative ISC populations have been identified, and this remarkable plasticity allows the intestine to rapidly respond to both the local environment and to damage. However, the mediators of such plasticity are still largely unknown. Using intestinal organoids and mouse models, we show that upon ribosome impairment (driven by Rptor deletion, amino acid starvation, or low dose cyclohexamide treatment) ISCs gain an Lgr5-negative, fetal-like identity. This is accompanied by a rewiring of metabolism. Our findings suggest that the ribosome can act as a sensor of nutrient availability, allowing ISCs to respond to the local nutrient environment. Mechanistically, we show that this phenotype requires the activation of ZAKɑ, which in turn activates YAP, via SRC. Together, our data reveals a central role for ribosome dynamics in intestinal stem cells, and identify the activation of ZAKɑ as a critical mediator of stem cell identity.

Identifying ribosome heterogeneity using ribosome profiling.

Recent studies have revealed multiple mechanisms that can lead to heterogeneity in ribosomal composition. This heterogeneity can lead to preferential translation of specific panels of mRNAs, and is defined in large part by the ribosomal protein (RP) content, amongst other things. However, it is currently unknown to what extent ribosomal composition is heterogeneous across tissues, which is compounded by a lack of tools available to study it. Here we present dripARF, a method for detecting differential RP incorporation into the ribosome using Ribosome Profiling (Ribo-seq) data. We combine the 'waste' rRNA fragment data generated in Ribo-seq with the known 3D structure of the human ribosome to predict differences in the composition of ribosomes in the material being studied. We have validated this approach using publicly available data, and have revealed a potential role for eS25/RPS25 in development. Our results indicate that ribosome heterogeneity can be detected in Ribo-seq data, providing a new method to study this phenomenon. Furthermore, with dripARF, previously published Ribo-seq data provides a wealth of new information, allowing the identification of RPs of interest in many disease and normal contexts. dripARF is available as part of the ARF R package and can be accessed through https://github.com/fallerlab/ARF.

Severity of the S1251N allele in cystic fibrosis is affected by the presence of the F508C variant in cis.

BACKGROUND: In cystic fibrosis (CF), genotype-phenotype correlation is complicated by the large number of CFTR variants, the influence of modifier genes, environmental effects, and the existence of complex alleles. We document the importance of complex alleles, in particular the F508C variant present in cis with the S1251N disease-causing variant, by detailed analysis of a patient with CF, with the [S1251N;F508]/G542X genotype and a very mild phenotype, contrasting it to that of four subjects with the [S1251N;F508C]/F508del genotype and classical CF presentation. METHODS: Genetic differences were identified by Sanger sequencing and CFTR function was quantified using rectal organoids in rectal organoid morphology analysis (ROMA) and forskolin-induced swelling (FIS) assays. CFTR variants were further characterised in CF bronchial epithelial (CFBE) cell lines. The impact of involved amino acid changes in the CFTR 3D protein structure was evaluated. RESULTS: Organoids of the patient [S1251N;F508] with mild CF phenotype confirmed the CF diagnosis but showed higher residual CFTR function compared to the four others [S1251N;F508C]. CFBE cell lines showed a decrease in [S1251N;F508C]-CFTR function but not in processing when compared to [S1251N;F508]-CFTR. Analysis of the 3D CFTR structure suggested an additive deleterious effect of the combined presence of S1251N and F508C with respect to NBD1-2 dimerisation. CONCLUSIONS: In vitro and in silico data show that the presence of F508C in cis with S1251N decreases CFTR function without affecting processing. Complex CFTR alleles play a role in clinical phenotype and their identification is relevant in the context of personalised medicine for each patient with CF.

Rescue of Mutant CFTR Trafficking Defect by the Investigational Compound MCG1516A.

Although some therapeutic progress has been achieved in developing small molecules that correct F508del-CFTR defects, the mechanism of action (MoA) of these compounds remain poorly elucidated. Here, we investigated the effects and MoA of MCG1516A, a newly developed F508del-CFTR corrector. MCG1516A effects on wild-type (WT) and F508del-CFTR were assessed by immunofluorescence microscopy, and biochemical and functional assays both in cell lines and in intestinal organoids. To shed light on the MoA of MCG1516A, we evaluated its additivity to the FDA-approved corrector VX-661, low temperature, genetic revertants of F508del-CFTR (G550E, R1070W, and 4RK), and the traffic-null variant DD/AA. Finally, we explored the ability of MCG1516A to rescue trafficking and function of other CF-causing mutations. We found that MCG1516A rescues F508del-CFTR with additive effects to VX-661. A similar behavior was observed for WT-CFTR. Under low temperature incubation, F508del-CFTR demonstrated an additivity in processing and function with VX-661, but not with MCG1516A. In contrast, both compounds promoted additional effects to low temperature to WT-CFTR. MCG1516A demonstrated additivity to genetic revertant R1070W, while VX-661 was additive to G550E and 4RK. Nevertheless, none of these compounds rescued DD/AA trafficking. Both MCG1516A and VX-661 rescued CFTR processing of L206W- and R334W-CFTR with greater effects when these compounds were combined. In summary, the absence of additivity of MCG1516A to genetic revertant G550E suggests a putative binding site for this compound on NBD1:NBD2 interface. Therefore, a combination of MCG1516A with compounds able to rescue DD/AA traffic, or mimicking the actions of revertant R1070W (e.g., VX-661), could enhance correction of F508del-CFTR defects.

Experiences of parent-adolescent dyads regarding a Facebook-based intervention to improve overweight/obesity treatment in adolescents: A qualitative study.

APOLO-Teens is a Facebook-based psychological intervention aiming to optimize hospital treatment for adolescents with overweight/obesity. The present qualitative study aims to explore (1) how adolescents experienced participation in APOLO-Teens and (2) how parents perceived adolescents' participation. Sixteen adolescent-parent dyads were interviewed by telephone using semistructured guides. An inductive approach of thematic analysis was used to analyze data by two independent codifiers. The consensus was used to resolve differences in coding/themes, and two independent auditors reviewed the codes and the themes proposed. We identified four themes from adolescents' interviews, namely, expectations, perception of outcomes, participation in the intervention, and sharing of acquired knowledge. From parents' interviews, we identified five themes: expectations for son/daughter participation, perception of adolescents' outcomes, son/daughter participation, parental role, and use of social networks in intervention programs for adolescents. Both elements of the dyad indicated that adolescents' participation in APOLO-Teens contributed to favorable outcomes, further highlighting the use of online interventions to complement the hospital treatment of adolescents with overweight/obesity. Future studies should address the viewpoints of adolescents and parents in the design of Facebook-based interventions, namely, to implement tailored, shorter, less time-demanding interventions that favor engagement between participants and parental involvement.

The impact of COVID-19 lockdown on disordered eating behaviors: the mediation role of psychological distress.

PURPOSE: This study aimed to explore the early associations between the experienced psychosocial impact of the COVID-19 pandemic crisis during lockdown, depressive symptomatology, anxiety/stress levels, and disordered eating behaviors in adults during a first COVID-19 lockdown period. METHODS: This was a community-based cross-sectional study assessing 254 Portuguese adults (82.7% women; 35.82 ± 11.82 years) 1 week after the end of the first mandatory COVID-19 lockdown in Portugal. An online survey was conducted to evaluate psychological distress, disordered eating, and psychosocial impact of the COVID-19 pandemic. Pearson correlations and Structural Equation Modeling were performed. RESULTS: Participants reported the presence of meal skipping (52.8%), grazing eating behavior (80.9%), overeating (81.0%), loss of control over eating (47.2%), and binge eating episodes (39.2%) during lockdown. Structural equation modeling analyses, controlling for age and sex, indicated that there was a significant indirect effect of the experienced psychosocial impact of COVID-19 pandemic on disordered eating behaviors mediated through psychological distress. CONCLUSION: The psychosocial impact of the COVID-19 pandemic crisis may lead to disordered eating, and this relation may occur through the elevation of psychological distress. These findings can be used to inform interventions, to enhance mental health and manage disordered eating during similar future situations. Level of evidence V: cross-sectional descriptive study.

Intuitive eating Scale-2: Factor structure and associations with disordered eating, impulsivity and quality of life in adolescents with overweight/obesity.

OBJECTIVE: The Intuitive Eating Scale-2 (IES-2) has been shown to be a valid tool to assess the capability of eating in reaction to natural hunger/satiety cues. However, its factor structure seems to differ in function of cultural/socioeconomic backgrounds, and its psychometric properties among the adolescents with overweight/obesity (BMI-for-age percentile >85th) have not been examined yet. Thus, this study aims to 1) investigating the factorial structure/psychometric properties of IES-2 in adolescents with overweight/obesity; and 2) exploring the associations between impulsivity, quality of life disordered and intuitive eating. METHODS: A total of 202 Portuguese adolescents (124 girls; 78 boys; 12-19 years) under weight-loss treatment with a mean BMI z-score of 2.41 (SD = 0.75) participated in this study. The IES-2 factor structure was explored by confirmatory factor analysis and bifactor models. Test-retest reliability analyses were performed over 6 months (n = 41) and associations between the variables under study were explored. RESULTS: Confirmatory factor analyses with posthoc modifications resulted in a bifactor model with acceptable fit supporting one general factor (intuitive eating) and three specific factors (IES-2 subscales). The "Unconditional Permission to Eat" subscale could not be replicated in this sample. Test-retest reliability analyses suggested good temporal stability. Intuitive eating scores were negatively associated with grazing eating behavior and impulsivity (negative urgency) and positively linked to quality of life. CONCLUSIONS: An adjusted version of IES-2 can be an appropriate measure for assessing intuitive eating levels in adolescents with overweight/obesity. Research on intuitive eating has the potential to enhance pediatric weight-loss interventions.

Synergy in Cystic Fibrosis Therapies: Targeting SLC26A9.

SLC26A9, a constitutively active Cl- transporter, has gained interest over the past years as a relevant disease modifier in several respiratory disorders including Cystic Fibrosis (CF), asthma, and non-CF bronchiectasis. SLC26A9 contributes to epithelial Cl- secretion, thus preventing mucus obstruction under inflammatory conditions. Additionally, SLC26A9 was identified as a CF gene modifier, and its polymorphisms were shown to correlate with the response to drugs modulating CFTR, the defective protein in CF. Here, we aimed to investigate the relationship between SLC26A9 and CFTR, and its role in CF pathogenesis. Our data show that SLC26A9 expression contributes to enhanced CFTR expression and function. While knocking-down SLC26A9 in human bronchial cells leads to lower wt- and F508del-CFTR expression, function, and response to CFTR correctors, the opposite occurs upon its overexpression, highlighting SLC26A9 relevance for CF. Accordingly, F508del-CFTR rescue by the most efficient correctors available is further enhanced by increasing SLC26A9 expression. Interestingly, SLC26A9 overexpression does not increase the PM expression of non-F508del CFTR traffic mutants, namely those unresponsive to corrector drugs. Altogether, our data indicate that SLC26A9 stabilizes CFTR at the ER level and that the efficacy of CFTR modulator drugs may be further enhanced by increasing its expression.

Integrity and Stability of PTC Bearing CFTR mRNA and Relevance to Future Modulator Therapies in Cystic Fibrosis.

Major advances have recently been made in the development and application of CFTR (cystic fibrosis transmembrane conductance regulator) mutation class-specific modulator therapies, but to date, there are no approved modulators for Class I mutations, i.e., those introducing a premature termination codon (PTC) into the CFTR mRNA. Such mutations induce nonsense-mediated decay (NMD), a cellular quality control mechanism that reduces the quantity of PTC bearing mRNAs, presumably to avoid translation of potentially deleterious truncated CFTR proteins. The NMD-mediated reduction of PTC-CFTR mRNA molecules reduces the efficacy of one of the most promising approaches to treatment of such mutations, namely, PTC readthrough therapy, using molecules that induce the incorporation of near-cognate amino acids at the PTC codon, thereby enabling translation of a full-length protein. In this study, we measure the effect of three different PTC mutations on the abundance, integrity, and stability of respective CFTR mRNAs, using CFTR specific RT-qPCR-based assays. Altogether, our data suggest that optimized rescue of PTC mutations has to take into account (1) the different steady-state levels of the CFTR mRNA associated with each specific PTC mutation; (2) differences in abundance between the 3' and 5' regions of CFTR mRNA, even following PTC readthrough or NMD inhibition; and (3) variable effects on CFTR mRNA stability for each specific PTC mutation.

Oncogene-dependent sloppiness in mRNA translation.

mRNA translation is a highly conserved and tightly controlled mechanism for protein synthesis. Despite protein quality control mechanisms, amino acid shortage in melanoma induces aberrant proteins by ribosomal frameshifting. The extent and the underlying mechanisms related to this phenomenon are yet unknown. Here, we show that tryptophan depletion-induced ribosomal frameshifting is a widespread phenomenon in cancer. We termed this event sloppiness and strikingly observed its association with MAPK pathway hyperactivation. Sloppiness is stimulated by RAS activation in primary cells, suppressed by pharmacological inhibition of the oncogenic MAPK pathway in sloppy cells, and restored in cells with acquired resistance to MAPK pathway inhibition. Interestingly, sloppiness causes aberrant peptide presentation at the cell surface, allowing recognition and specific killing of drug-resistant cancer cells by T lymphocytes. Thus, while oncogenes empower cancer progression and aggressiveness, they also expose a vulnerability by provoking the production of aberrant peptides through sloppiness.

Eating behaviors and weight outcomes in bariatric surgery patients amidst COVID-19.

BACKGROUND: Recent studies suggest that eating habits are an area particularly affected by the lockdown imposed by many countries to curb the COVID-19 epidemic. Individuals that received bariatric surgery may represent a particularly susceptible population to the adverse effects of lockdown for its potential impact on eating, psychological, and weight loss outcomes. OBJECTIVES: This study seeks to investigate the incremental impact of COVID-19 lockdown on treatment outcomes of postbariatric patients in the risk period for weight regain. SETTING: Main hospital center. METHODS: This work uses data from an ongoing longitudinal study of bariatric patients assessed before surgery (T0), 1.5 years after sugery (T1), and 3 years after surgery (T2). Two independent groups were compared: the COVID-19_Group (n = 35) where T0 and T1 assessments were conducted before the pandemic started and T2 assessment was conducted at the end of the mandatory COVID-19 lockdown; and the NonCOVID-19_Group (n = 66), covering patients who completed T0, T1, and T2 assessments before the epidemic began. Assessment included self-report measures for disordered eating, negative urgency, depression, anxiety, stress, and weight outcomes. RESULTS: General linear models for repeated measures showed that the COVID-19_Group presented significantly higher weight concern (F = 8.403, P = .005, ƞ2p = .094), grazing behavior (F = 7.166, P = .009, ƞ2p = .076), and negative urgency (F = 4.522, P = .036, ƞ2p = .05) than the NonCOVID-19_Group. The COVID-19_Group also showed less total weight loss (F = 4.029, P = .05, ƞ2p = .04) and larger weight regain at T2, with more COVID-19_Group participants experiencing excessive weight regain (20% versus 4.5%). CONCLUSION: These results show evidence for the impact of the coronavirus outbreak on eating-related psychopathology and weight outcomes in postbariatric surgery patients.