Why does decreased likeability not deter adolescent bullying perpetrators?

This study examines why the lower likeability of bullying perpetrators does not deter them from engaging in bullying behavior, by testing three hypotheses: (a) bullying perpetrators are unaware that they are disliked, (b) they value popularity more than they value likeability, (c) they think that they have nothing to lose in terms of likeability, as they believe that their targets and other classmates would dislike them anyway, regardless of their behavior. The first two hypotheses were examined in Study 1 (1,035 Dutch adolescents, M age = 14.15) and the third hypothesis was examined in Study 2 (601 Dutch adolescents, M age = 12.92). Results from regression analyses showed that those higher in bullying were not more likely to overestimate their likeability. However, they were more likely than others to find being popular more important than being liked. Moreover, those higher in bullying were more likely to endorse the belief that the victimized student or the other classmates would have disliked a bullying protagonist (in vignettes of hypothetical bullying incidents) before any bullying started. These findings suggest that adolescent bullying perpetrators may not be deterred by the costs of bullying in terms of likeability, possibly because they do not value likeability that much (Hypothesis 2), and because they believe they hardly have any likeability to lose (Hypothesis 3).</p

An African-specific haplotype in MRGPRX4 is associated with menthol cigarette smoking

In the U.S., more than 80% of African-American smokers use mentholated cigarettes, compared to less than 30% of Caucasian smokers. The reasons for these differences are not well understood. To determine if genetic variation contributes to mentholated cigarette smoking, we performed an exome-wide association analysis in a multiethnic population-based sample from Dallas, TX (N = 561). Findings were replicated in an independent cohort of African Americans from Washington, DC (N = 741). We identified a haplotype of MRGPRX4 (composed of rs7102322[G], encoding N245S, and rs61733596[G], T43T), that was associated with a 5-to-8 fold increase in the odds of menthol cigarette smoking. The variants are present solely in persons of African ancestry. Functional studies indicated that the variant G protein-coupled receptor encoded by MRGPRX4 displays reduced agonism in both arrestin-based and G protein-based assays, and alteration of agonism by menthol. These data indicate that genetic variation in MRGPRX4 contributes to inter-individual and inter-ethnic differences in the preference for mentholated cigarettes, and that the existence of genetic factors predisposing vulnerable populations to mentholated cigarette smoking can inform tobacco control and public health policies

Bidirectional Associations between Popularity, Popularity Goal, and Aggression, Alcohol Use and Prosocial Behaviors in Adolescence: A 3-Year Prospective Longitudinal Study

Adolescents’ popularity and popularity goal have been shown to be related to their aggression and alcohol use. As intervention efforts increasingly aim to focus on prosocial alternatives for youth to gain status, it is essential to have a comprehensive understanding of how popularity and popularity goal are associated with aggression and substance use as well as prosocial behaviors over time. The current study examined the bidirectional associations of aggression (overt and relational aggression), alcohol use, and prosocial behavior with popularity and popularity goal in adolescence across 3 years using cross-lagged panel analyses. Participants were 839 Dutch adolescents (Mage=13.36, SD=0.98; 51.3% girls). The results indicated that popularity was consistently positively associated with popularity goal, but popularity goal did not significantly predict subsequent popularity. Popularity positively predicted elevated aggression and alcohol use, but lower levels of prosocial behavior. For the full sample, alcohol use and overt aggression in grade 7 both predicted subsequent popularity in grade 8. However, when considering gender differences, overt aggression no longer was a significant predictor of popularity. These results were discussed in terms of the dynamic interplay between popularity, popularity goal, and behaviors, and in terms of implications for prevention and intervention efforts.</p

Adolescent Victim Types Across the Popularity Status Hierarchy: Differences in Internalizing Symptoms

Previous studies have called attention to the fact that popular youth are not immune to peer victimization, suggesting there is heterogeneity in the popularity of victims. Yet, no study to date has determined whether victims with different levels of popularity status can be identified using person-oriented analysis. Such analysis is critically needed to confirm the existence of popular victims. Further, there remains a paucity of research on internalizing indices of such popular victims, especially compared to other victim and non-victim groups. To address this gap in the research literature, the current study used latent profile analysis to identify subgroups of victims based on victimization (self- and peer-report) and popularity (peer-report). This study sought to verify the existence of popular victims and to compare victim subgroups on loneliness and self-esteem. Participants were 804 Dutch adolescents (50.2% boys, Mage = 13.65 years, ranging from 11.29 to 16.75 years). The results revealed six subgroups, including a group of popular self-identified victims. Popular self-identified victims were generally less lonely than other victims, but had higher loneliness and lower self-esteem than non-victims. Implications are discussed for understanding the victimization experiences of high-status youth

A global analysis of how human infrastructure squeezes sandy coasts

Coastal ecosystems provide vital services, including water storage, carbon sequestration, biodiversity, and coastal protection. Human disturbances, however, cause massive losses. The most direct impact is habitat destruction through infrastructure development, restricting the space available to coastal ecosystems and impeding their capacity to adapt to sea level rise by landward retreat – a phenomenon called ‘coastal squeeze’. While shoreline retreat is intensively studied, coastal congestion through infrastructure remains unquantified. Here we calculated the distance to the nearest human-made structure along 263,900 transects worldwide to show that infrastructure occurs at a 560-meter median distance from the shoreline. Moreover, we find that 18% of global sandy shores harbour less than 100 m of infrastructure-free space, and that 14-17% of the unimpacted space may drown by 2100 according to sea level rise projections. Further analyses show that population density and gross domestic product explain 40-44% of observed squeeze variation, emphasizing the intensifying pressure imposed as countries develop and populations expand. Encouragingly, we find that nature reserves relieve squeezing by 3-5 times, illustrating their effectiveness. Yet, at present only 16% of world’s sandy shores has a protected status. We therefore argue that expansion of nature reserves could be key to preserving coastal resilience to sea level rise

Multi-omics integration identifies key upstream regulators of pathomechanisms in hypertrophic cardiomyopathy due to truncating MYBPC3 mutations

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common genetic disease of the cardiac muscle, frequently caused by mutations in MYBPC3. However, little is known about the upstream pathways and key regulators causing the disease. Therefore, we employed a multi-omics approach to study the pathomechanisms underlying HCM comparing patient hearts harboring MYBPC3 mutations to control hearts. RESULTS: Using H3K27ac ChIP-seq and RNA-seq we obtained 9310 differentially acetylated regions and 2033 differentially expressed genes, respectively, between 13 HCM and 10 control hearts. We obtained 441 differentially expressed proteins between 11 HCM and 8 control hearts using proteomics. By integrating multi-omics datasets, we identified a set of DNA regions and genes that differentiate HCM from control hearts and 53 protein-coding genes as the major contributors. This comprehensive analysis consistently points toward altered extracellular matrix formation, muscle contraction, and metabolism. Therefore, we studied enriched transcription factor (TF) binding motifs and identified 9 motif-encoded TFs, including KLF15, ETV4, AR, CLOCK, ETS2, GATA5, MEIS1, RXRA, and ZFX. Selected candidates were examined in stem cell-derived cardiomyocytes with and without mutated MYBPC3. Furthermore, we observed an abundance of acetylation signals and transcripts derived from cardiomyocytes compared to non-myocyte populations. CONCLUSIONS: By integrating histone acetylome, transcriptome, and proteome profiles, we identified major effector genes and protein networks that drive the pathological changes in HCM with mutated MYBPC3. Our work identifies 38 highly affected protein-coding genes as potential plasma HCM biomarkers and 9 TFs as potential upstream regulators of these pathomechanisms that may serve as possible therapeutic targets

Dissemination of extensively drug-resistant NDM-producing Providencia stuartii in Europe linked to patients transferred from Ukraine, March 2022 to March 2023

BackgroundThe war in Ukraine led to migration of Ukrainian people. Early 2022, several European national surveillance systems detected multidrug-resistant (MDR) bacteria related to Ukrainian patients.AimTo investigate the genomic epidemiology of New Delhi metallo-β-lactamase (NDM)-producing Providencia stuartii from Ukrainian patients among European countries.MethodsWhole-genome sequencing of 66 isolates sampled in 2022-2023 in 10 European countries enabled whole-genome multilocus sequence typing (wgMLST), identification of resistance genes, replicons, and plasmid reconstructions. Five blaNDM-1-carrying-P. stuartii isolates underwent antimicrobial susceptibility testing (AST). Transferability to Escherichia coli of a blaNDM-1-carrying plasmid from a patient strain was assessed. Epidemiological characteristics of patients with NDM-producing P. stuartii were gathered by questionnaire.ResultswgMLST of the 66 isolates revealed two genetic clusters unrelated to Ukraine and three linked to Ukrainian patients. Of these three, two comprised blaNDM-1-carrying-P. stuartii and the third blaNDM-5-carrying-P. stuartii. The blaNDM-1 clusters (PstCluster-001, n = 22 isolates; PstCluster-002, n = 8 isolates) comprised strains from seven and four countries, respectively. The blaNDM-5 cluster (PstCluster-003) included 13 isolates from six countries. PstCluster-001 and PstCluster-002 isolates carried an MDR plasmid harbouring blaNDM-1,blaOXA-10, blaCMY-16, rmtC and armA, which was transferrable in vitro and, for some Ukrainian patients, shared by other Enterobacterales. AST revealed PstCluster-001 isolates to be extensively drug-resistant (XDR), but susceptible to cefiderocol and aztreonam-avibactam. Patients with data on age (n = 41) were 19-74 years old; of 49 with information on sex, 38 were male.ConclusionXDR P. stuartii were introduced into European countries, requiring increased awareness and precautions when treating patients from conflict-affected areas.</p

Emerging Themes and Future Directions of Multi-Sector Nexus Research and Implementation

Water, energy, and food are all essential components of human societies. Collectively, their respective resource systems are interconnected in what is called the “nexus”. There is growing consensus that a holistic understanding of the interdependencies and trade-offs between these sectors and other related systems is critical to solving many of the global challenges they present. While nexus research has grown exponentially since 2011, there is no unified, overarching approach, and the implementation of concepts remains hampered by the lack of clear case studies. Here, we present the results of a collaborative thought exercise involving 75 scientists and summarize them into 10 key recommendations covering: the most critical nexus issues of today, emerging themes, and where future efforts should be directed. We conclude that a nexus community of practice to promote open communication among researchers, to maintain and share standardized datasets, and to develop applied case studies will facilitate transparent comparisons of models and encourage the adoption of nexus approaches in practice

In silico design of novel probes for the atypical opioid receptor MRGPRX2

The primate-exclusive MRGPRX2 G protein-coupled receptor (GPCR) has been suggested to modulate pain and itch. Despite putative peptide and small molecule MRGPRX2 agonists, selective nanomolar potency probes have not yet been reported. To identify a MRGPRX2 probe, we first screened 5,695 small molecules and found many opioid compounds activated MRGPRX2, including (−)- and (+)-morphine, hydrocodone, sinomenine, dextromethorphan and the prodynorphin-derived peptides, dynorphin A, dynorphin B, and α- and β-neoendorphin. We used these to select for mutagenesis-validated homology models and docked almost 4 million small molecules. From this docking, we predicted ZINC-3573, which represents a potent MRGPRX2-selective agonist, showing little activity against 315 other GPCRs and 97 representative kinases, and an essentially inactive enantiomer. ZINC-3573 activates endogenous MRGPRX2 in a human mast cell line inducing degranulation and calcium release. MRGPRX2 is a unique atypical opioid-like receptor important for modulating mast cell degranulation, which can now be specifically modulated with ZINC-3573