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Viruses target mitochondria to promote their replication, and infection-induced stress during the progression of infection leads to the regulation of antiviral defenses and mitochondrial metabolism which are opposed by counteracting viral factors. The precise structural and functional changes that underlie how mitochondria react to the infection remain largely unclear. Here we show extensive transcriptional remodeling of protein-encoding host genes involved in the respiratory chain, apoptosis, and structural organization of mitochondria as herpes simplex virus type 1 lytic infection proceeds from early to late stages of infection. High-resolution microscopy and interaction analyses unveiled infection-induced emergence of rough, thin, and elongated mitochondria relocalized to the perinuclear area, a significant increase in the number and clustering of endoplasmic reticulum-mitochondria contact sites, and thickening and shortening of mitochondrial cristae. Finally, metabolic analyses demonstrated that reactivation of ATP production is accompanied by increased mitochondrial Ca2+ content and proton leakage as the infection proceeds. Overall, the significant structural and functional changes in the mitochondria triggered by the viral invasion are tightly connected to the progression of the virus infection.

Abstract Background Among adolescents, symptoms of generalized anxiety disorder (GAD) and social anxiety disorder (SAD) are not only clinically significant but also continuingly increasing. During adolescence, individuals begin to establish distinct, self-determined lifestyle patterns. This study seeks to identify the associations between such lifestyle factors and the prevalence of GAD and SAD symptoms. Methods The analyzable sample was based on a cross-sectional, nationally representative survey of Finnish 14–18 year old students from comprehensive schools, general upper secondary schools, and vocational institutions. The sample consisted of 60,252 boys and 71,118 girls, with the mean age of 16.05 years (standard deviation 1.06). Symptoms were identified using the GAD-7 (cutpoint of 10), the Mini-SPIN (cutpoint of 6), and the PHQ-2 (cutpoint of 3). Logistic regression models for both GAD and SAD symptoms were stratified by comorbidity group variables. Results GAD symptoms were closely related to excessive internet use and decreased sleep duration among adolescents, regardless of comorbidity with depression or SAD. SAD symptoms were associated with excessive internet use and a lack of intense exercise, independent of comorbid depression or GAD. Conclusions The findings underscore the importance of considering lifestyle factors when developing interventions to mitigate GAD and SAD symptoms in adolescents. Interventions and policy recommendations aiming at improving adolescents’ health behaviour and mental health should take into account the intertwining of these factors.

This study examines the extent to which local au­thorities in rural North-West Romania adhere to the requirements set forth in Law no. 544 of 2001, which mandates the ex officio public information disclo­sure online. The findings suggest a relatively low level of transparency, with notable discrepancies ob­served across communes. While larger communes exhibited slightly elevated levels of compliance, pop­ulation size exerted a limited influence on transpar­ency. Additionally, the study revealed no statistically significant correlation between the gender of mayors and transparency. This may be attributed to the lim­ited representation of female mayors in the sample. Similarly, while the presence of businesses demon­strated some influence on transparency, it was not a robust predictor. These findings underscore the ne­cessity for more robust enforcement mechanisms, including penalties for non-compliance, to guarantee compliance with transparency laws. Furthermore, the study highlights the necessity of considering a broader array of factors, including local governance practices, institutional capacity, and citizen engage­ment, when evaluating transparency outcomes. It would be beneficial for future research to expand to other regions and consider a longitudinal approach to monitor changes over time. The study under­scores the pivotal role of transparency in cultivating public trust, curbing corruption, and strengthening democratic governance.

Abstract Objective The objective of the study is to characterize the pathomechanisms underlying actininopathies. Distal myopathies are a group of rare, inherited muscular disorders characterized by progressive loss of muscle fibers that begin in the distal parts of arms and legs. Recently, variants in a new disease gene, ACTN2, have been shown to cause distal myopathy. ACTN2, a gene previously only associated with cardiomyopathies, encodes alpha‐actinin‐2, a protein expressed in both cardiac and skeletal sarcomeres. The primary function of alpha‐actinin‐2 is to link actin and titin to the sarcomere Z‐disk. New ACTN2 variants are continuously discovered; however, the clinical significance of many variants remains unknown. Thus, lack of clear genotype–phenotype correlations in ACTN2‐related diseases, actininopathies, persists. Methods Functional characterization in C2C12 cell model of several ACTN2 variants is conducted, including frameshift and missense variants associated with dominant and recessive actininopathies. We assess the genotype–phenotype correlations of actininopathies using clinical data from several patients carrying these variants. Results The results show that the missense variants associated with a recessive form of actininopathy do not cause detectable alpha‐actinin‐2 aggregates in the cell model. Conversely, dominant frameshift variants causing a protein extension do form alpha‐actinin‐2 aggregates. Interpretation The results suggest that alpha‐actinin‐2 aggregation is the disease mechanism underlying some dominant actininopathies, and thus, we recommend that protein‐extending frameshift variants in ACTN2 should be classified as pathogenic. However, this mechanism is likely elicited by only a limited number of variants. Alternative functional characterization methods should be explored to further investigate other molecular mechanisms underlying actininopathies.

Abstract Background Klebsiella aerogenes is an opportunistic pathogen that causes a wide variety of infections. Due to the rising problem of antibiotic resistance, novel antibiotics and strategies to combat bacterial infections are needed. Host-specific bacteriophages are natural enemies of bacteria and can be used in phage therapy as an alternative form of treatment against bacterial infections. Jumbo phages are defined as phages with genomes larger than 200 kb. Relatively few studies have been done on jumbo phages compared to smaller phages. Results A novel phage, fENko-Kae01, was isolated from a commercial phage cocktail. Genomic analysis revealed that fENko-Kae01 is a lytic jumbo phage with a 360 kb genome encoding 578 predicted genes. No highly similar phage genomes were identified and fENko-Kae01 may be a completely new genus representative. No known genes associated with lysogenic life cycle, bacterial virulence, or antibiotic resistance were identified. The phage had myovirus morphology and a narrow host range. Phage resistant bacterial mutants emerged under phage selection. Whole genome sequencing revealed that the biogenesis of the flagellum was affected in four mutants and the lack of functional flagellum was confirmed in motility assays. Furthermore, phage fENKo-Kae01 failed to adsorb on the non-motile mutants indicating that the bacterial flagellum is the phage-binding receptor. Conclusions fENko-Kae01 is a novel jumbo bacteriophage that is considered safe for phage therapy. fENko-Kae01 uses the flagellum as the phage-binding receptor and may represent a completely novel genus.

This study explored how doctoral educators apply a radial blended collaborative (RBC) strategy to teach EFL speaking. This study used a narrative case study design and a qualitative approach. In doing so, teachers employed eight RBCs' strategies: raising collaboration awareness, forming groups based on 21st-century skills, using controlled-chosen topics and theme-based prior knowledge, employing snowball questioning techniques, engaging in role-play in different contexts, conducting peer evaluations, and providing oral and written feedback. This study found that technology integration, such as WhatsApp, Zoom Meeting, Google Classroom, and electronic mail, enhanced the learning experience, whereas pooling WhatsApp messages was used to direct the chosen discussion topics. The results demonstrated that RBC significantly improved students' speaking performance across four instructional dimensions: collaborative awareness, active learning, classroom interaction, and technological integration. Future research should aim to enhance spoken communication by integrating technology in assessments and fostering collaborative learning environments.

Summary: Background: Although the incidence and case-fatality of subarachnoid haemorrhage (SAH) vary within countries, few countries have reported nationwide rates, especially for multi-ethnic populations. We assessed the nationwide incidence and case-fatality of SAH in New Zealand (NZ) and explored variations by sex, district, ethnicity and time. Methods: We used administrative health data from the national hospital discharge and cause-of-death collections to identify hospitalised and fatal non-hospitalised aneurysmal SAHs in NZ between 2001 and 2018. For validation, we compared these administrative data to those of two prospective Auckland Regional Community Stroke Studies. We subsequently estimated the incidence and case-fatality of SAH and calculated adjusted rate ratios (RR) with 95% confidence intervals to assess differences between sub-populations. Findings: Over 78,187,500 cumulative person-years, we identified 5371 SAHs (95% sensitivity and 85% positive predictive values) resulting in an annual age-standardised nationwide incidence of 8.2/100,000. In total, 2452 (46%) patients died within 30 days after SAH. Compared to European/others, Māori had greater incidence (RR = 2.23 (2.08–2.39)) and case-fatality (RR = 1.14 (1.06–1.22)), whereas SAH incidence was also greater in Pacific peoples (RR = 1.40 (1.24–1.59)) but lesser in Asians (RR = 0.79 (0.71–0.89)). By domicile, age-standardised SAH incidence varied between 6.3–11.5/100,000 person-years and case fatality between 40 and 57%. Between 2001 and 2018, the SAH incidence of NZ decreased by 34% and the case fatality by 12%. Interpretation: Since the incidence and case-fatality of SAH varies considerably between regions and ethnic groups, caution is advised when generalising findings from focused geographical locations for public health planning, especially in multi-ethnic populations. Funding: NZ Health Research Council.