Telomerase therapy attenuates cardiotoxic effects of doxorubicin.

Doxorubicin is one of the most potent chemotherapeutic agents. However, its clinical use is restricted due to the severe risk of cardiotoxicity, partially attributed to elevated production of reactive oxygen species (ROS). Telomerase canonically maintains telomeres during cell division but is silenced in adult hearts. In non-dividing cells such as cardiomyocytes, telomerase confers pro-survival traits, likely owing to the detoxification of ROS. Therefore, we hypothesized that pharmacological overexpression of telomerase may be used as a therapeutic strategy for the prevention of doxorubicin-induced cardiotoxicity. We used adeno-associated virus (AAV)-mediated gene therapy for long-term expression of telomerase in in vitro and in vivo models of doxorubicin-induced cardiotoxicity. Overexpression of telomerase protected the heart from doxorubicin-mediated apoptosis and rescued cardiac function, which was accompanied by preserved cardiomyocyte size. At the mechanistic level, we observed altered mitochondrial morphology and dynamics in response to telomerase expression. Complementary in vitro experiments confirmed the anti-apoptotic effects of telomerase overexpression in human induced pluripotent stem cell-derived cardiomyocytes after doxorubicin treatment. Strikingly, elevated levels of telomerase translocated to the mitochondria upon doxorubicin treatment, which helped to maintain mitochondrial function. Thus, telomerase gene therapy could be a novel preventive strategy for cardiotoxicity by chemotherapy agents such as the anthracyclines.

Temporary adhesion of the proseriate flatworm Minona ileanae.

Flatworms can very rapidly attach to and detach from many substrates. In the presented work, we analysed the adhesive system of the marine proseriate flatworm Minona ileanae. We used light-, scanning- and transmission electron microscopy to analyse the morphology of the adhesive organs, which are located at the ventral side of the tail-plate. We performed transcriptome sequencing and differential RNA-seq for the identification of tail-specific transcripts. Using in situ hybridization expression screening, we identified nine transcripts that were expressed in the cells of the adhesive organs. Knock-down of five of these transcripts by RNA interference led to a reduction of the animal's attachment capacity. Adhesive proteins in footprints were confirmed using mass spectrometry and antibody staining. Additionally, lectin labelling of footprints revealed the presence of several sugar moieties. Furthermore, we determined a genome size of about 560 Mb for M. ileanae. We demonstrated the potential of Oxford Nanopore sequencing of genomic DNA as a cost-effective tool for identifying the number of repeats within an adhesive protein and for combining transcripts that were fragments of larger genes. A better understanding of the molecules involved in flatworm bioadhesion can pave the way towards developing innovative glues with reversible adhesive properties. This article is part of the theme issue 'Transdisciplinary approaches to the study of adhesion and adhesives in biological systems'.

Engaging Stakeholders From Volunteer-Led Out-of-School Time Programs in the Dissemination of Guiding Principles for Healthy Snacking and Physical Activity.

BACKGROUND: Little effort has focused on the role of volunteer-led out-of-school time (OST) programs (ie, enrichment and sports programs) as key environments for the promotion of healthy eating and physical activity habits among school-aged children. The Healthy Kids Out of School (HKOS) initiative developed evidence-based, practical guiding principles for healthy snacks, beverages, and physical activity. The goal of this case study was to describe the methods used to engage regional partners to understand how successful implementation and dissemination of these principles could be accomplished. COMMUNITY CONTEXT: HKOS partnered with volunteer-led programs from 5 OST organizations in Maine, Massachusetts, and New Hampshire to create a regional "learning laboratory." METHODS: We engaged partners in phases. In the first phase, we conducted focus groups with local volunteer program leaders; during the second phase, we held roundtable meetings with regional and state program administrators; and in the final phase, we conducted additional outreach to refine and finalize implementation strategies. OUTCOMES: Implementation strategies were developed based on themes and information that emerged. For enrichment programs, strategies included new patch and pin programs that were consistent with the organizations' infrastructure and usual practices. For sports programs, the main strategy was integration with online trainings for coaches. INTERPRETATION: Through the engagement process, we learned that dissemination of the guiding principles in these large and complex OST organizations was best accomplished by using implementation strategies that were customized, integrated, and aligned with goals and usual practices. The lessons learned can benefit future efforts to prevent obesity in complex environments.

Validation of the Out-of-School-Time Snacks, Beverages, and Physical Activity Questionnaire.

BACKGROUND: Recent research has highlighted the potential for out-of-school-time (OST) environments to impact children's energy balance. Expanding upon this evidence requires validated measures to assess nutrition and physical activity (PA) environments across large samples of OST programs. The aim of this study was to assess the criterion validity of the Out-of-School-Time Snacks, Beverages, and Physical Activity Questionnaire (OST-SBPA), an online questionnaire designed to measure OST nutrition and PA environments by program leaders' reports. METHODS: The study consisted of two samples of OST programs (total n=65). Objective data across program meetings were compared to program leaders' reports of usual snack, beverage, and PA offerings. All 65 programs provided snack and beverage data; PA data were available from 31 programs. Validity was assessed using percent agreement, Cohen's kappa, and Spearman's correlations. RESULTS: All OST-SBPA items demonstrated agreement above 60% when dichotomized (e.g., none/some versus most/all of the time for frequency items). Most OST-SBPA items were significantly correlated with objective data, including how often fresh and processed fruits and vegetables, salty snacks, sweet snacks, protein snacks, milk, juice, and sweetened beverages were offered and four PA measures (r=0.43-0.78; p<0.01), whereas one item, the frequency that water was offered, was not (r=0.13; p=0.37). The water item demonstrated validity once water from water fountains was recoded and not considered a program-provided beverage. CONCLUSIONS: These findings fill a gap in the literature through the validation of a brief questionnaire that can be used to assess OST nutrition and PA environments. The current results support the use of the OST-SBPA in studies aiming to assess and impact these environments.