RESUMEN
BACKGROUND: Even without weight loss, adults with obesity can greatly benefit from regular physical activity. The Physical Activity Self-efficacy (PAS) intervention is an online behavioral intervention newly developed to promote physical activity in adults with obesity by providing capability-enhancing learning opportunities. The objective of this manuscript is to describe the protocol for a feasibility study designed to investigate the feasibility and acceptability of implementing the PAS online intervention for adults with obesity recruited from a local weight management center in the United States of America (USA). METHODS: The study design is a prospective, double-blind, parallel-group individual randomized pilot trial. Thirty participants will be randomly assigned to the PAS group or usual care group to achieve a 1:1 group assignment. Recruitment of participants is scheduled to begin on 1 March 2024 at a local weight management center within a private healthcare system in the USA. There are six eligibility criteria for participation in this study (e.g., a body mass index ≥ 25.00 kg/m2). Eligibility verification and data collection will be conducted online. Three waves of data collection will take up to 14 weeks depending on participants' progress in the study. The primary feasibility outcomes in the study will be: (a) participation rate, (b) engagement behavior, and (c) a preliminary effect size estimate for the effect of the PAS intervention on physical activity. Instruments designed to measure demographic information, anthropometric characteristics, self-efficacy, and acceptability will be included in the survey battery. A research-grade accelerometer will be used to measure free-living physical activity objectively. Data will be analyzed using descriptive statistics and inferential statistical models under an intention-to-treat approach. DISCUSSION: Results are intended to inform the preparation of a future definitive randomized controlled trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05935111, registered 7 July 2023.
RESUMEN
Genetic variation in mitochondrial and nuclear genomes can perturb mitonuclear interactions and lead to phenotypic differences between individuals and populations. Despite their importance to most complex traits, it has been difficult to identify the interacting mitonuclear loci. Here, we present a novel advanced intercrossed population of Saccharomyces cerevisiae yeasts, called the Mitonuclear Recombinant Collection (MNRC), designed explicitly for detecting mitonuclear loci contributing to complex traits. For validation, we focused on mapping genes that contribute to the spontaneous loss of mitochondrial DNA (mtDNA) that leads to the petite phenotype in yeast. We found that rates of petite formation in natural populations are variable and influenced by genetic variation in nuclear DNA, mtDNA and mitonuclear interactions. We mapped nuclear and mitonuclear alleles contributing to mtDNA stability using the MNRC by integrating a term for mitonuclear epistasis into a genome-wide association model. We found that the associated mitonuclear loci play roles in mitotic growth most likely responding to retrograde signals from mitochondria, while the associated nuclear loci with main effects are involved in genome replication. We observed a positive correlation between growth rates and petite frequencies, suggesting a fitness tradeoff between mitotic growth and mtDNA stability. We also found that mtDNA stability was correlated with a mobile mitochondrial GC-cluster that is present in certain populations of yeast and that selection for nuclear alleles that stabilize mtDNA may be rapidly occurring. The MNRC provides a powerful tool for identifying mitonuclear interacting loci that will help us to better understand genotype-phenotype relationships and coevolutionary trajectories.
Asunto(s)
Epistasis Genética , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Estudio de Asociación del Genoma Completo , ADN Mitocondrial/genética , Mitocondrias/genéticaRESUMEN
The dietary specialist fruit fly Drosophila sechellia has evolved to specialize on the toxic fruit of its host plant Morinda citrifolia Toxicity of Morinda fruit is primarily due to high levels of octanoic acid (OA). Using RNA interference (RNAi), prior work found that knockdown of Osiris family genes Osiris 6 (Osi6), Osi7, and Osi8 led to increased susceptibility to OA in adult D. melanogaster flies, likely representing genes underlying a Quantitative Trait Locus (QTL) for OA resistance in D. sechellia While genes in this major effect locus are beginning to be revealed, prior work has shown at least five regions of the genome contribute to OA resistance. Here, we identify new candidate OA resistance genes by performing differential gene expression analysis using RNA-sequencing (RNA-seq) on control and OA-exposed D. sechellia flies. We found 104 significantly differentially expressed genes with annotated orthologs in D. melanogaster, including six Osiris gene family members, consistent with previous functional studies and gene expression analyses. Gene ontology (GO) term enrichment showed significant enrichment for cuticle development in upregulated genes and significant enrichment of immune and defense responses in downregulated genes, suggesting important aspects of the physiology of D. sechellia that may play a role in OA resistance. In addition, we identified five candidate OA resistance genes that potentially underlie QTL peaks outside of the major effect region, representing promising new candidate genes for future functional studies.
Asunto(s)
Caprilatos/química , Drosophila melanogaster/genética , Morinda/química , Receptores Odorantes/genética , Animales , Caprilatos/toxicidad , Drosophila melanogaster/efectos de los fármacos , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica/efectos de los fármacos , Morinda/toxicidad , Sitios de Carácter Cuantitativo/genética , Interferencia de ARN , Análisis de Secuencia de ARN , Especificidad de la Especie , Transcriptoma/efectos de los fármacos , Transcriptoma/genéticaRESUMEN
It is common for an intravascular catheter to be inserted to administer various types of therapy. Extravasation occurs frequently, and in the most severe cases plastic surgeons are often summoned to assess the extent of the injury and the possibility for reconstruction. The Department of Plastic and Reconstructive Surgery at Oslo University Hospital assesses approximately 15 severe cases of this type each year.
Asunto(s)
Extravasación de Materiales Terapéuticos y Diagnósticos , Algoritmos , Extravasación de Materiales Terapéuticos y Diagnósticos/patología , Extravasación de Materiales Terapéuticos y Diagnósticos/fisiopatología , Extravasación de Materiales Terapéuticos y Diagnósticos/prevención & control , Extravasación de Materiales Terapéuticos y Diagnósticos/terapia , Humanos , Factores de RiesgoRESUMEN
BACKGROUND: Rigorous study of mitochondrial functions and cell biology in the budding yeast, Saccharomyces cerevisiae has advanced our understanding of mitochondrial genetics. This yeast is now a powerful model for population genetics, owing to large genetic diversity and highly structured populations among wild isolates. Comparative mitochondrial genomic analyses between yeast species have revealed broad evolutionary changes in genome organization and architecture. A fine-scale view of recent evolutionary changes within S. cerevisiae has not been possible due to low numbers of complete mitochondrial sequences. RESULTS: To address challenges of sequencing AT-rich and repetitive mitochondrial DNAs (mtDNAs), we sequenced two divergent S. cerevisiae mtDNAs using a single-molecule sequencing platform (PacBio RS). Using de novo assemblies, we generated highly accurate complete mtDNA sequences. These mtDNA sequences were compared with 98 additional mtDNA sequences gathered from various published collections. Phylogenies based on mitochondrial coding sequences and intron profiles revealed that intraspecific diversity in mitochondrial genomes generally recapitulated the population structure of nuclear genomes. Analysis of intergenic sequence indicated a recent expansion of mobile elements in certain populations. Additionally, our analyses revealed that certain populations lacked introns previously believed conserved throughout the species, as well as the presence of introns never before reported in S. cerevisiae. CONCLUSIONS: Our results revealed that the extensive variation in S. cerevisiae mtDNAs is often population specific, thus offering a window into the recent evolutionary processes shaping these genomes. In addition, we offer an effective strategy for sequencing these challenging AT-rich mitochondrial genomes for small scale projects.
Asunto(s)
Genoma Mitocondrial , Saccharomyces cerevisiae/genética , Análisis de Secuencia de ADN/métodos , Secuencia Rica en At , Elementos Transponibles de ADN , ADN de Hongos/análisis , ADN Mitocondrial/análisis , Evolución Molecular , Filogenia , Saccharomyces cerevisiae/clasificaciónRESUMEN
Most axons in the mammalian brain are unmyelinated and thin with pre-synaptic specializations (boutons) along their entire paths. The parallel fibers in the cerebellum are examples of such axons. Unlike most thin axons they have only one branch point. The granule cell soma, where they originate, can fire bursts of action potentials with spike intervals of about 2 ms. An important question is whether the axons are able to propagate spikes with similarly short intervals. By using extracellular single-unit and population-recording methods we showed that parallel fibers faithfully conduct spikes at high frequencies over long distances. However, when adding 20 microm ZD7288 or 1 mm Cs(+), or reducing the temperature from 35 to 24 degrees C, the action potentials often failed even when successfully initiated. Ba(2+)(1 mm), which blocks Kir channels, did not reproduce these effects. The conduction velocity was reduced by ZD7288 but not by Ba(2+). This suggests that the parallel fibers have an H-current that is active at rest and that is important for their frequency-following properties. Interestingly, failures occurred only when the action potential had to traverse the axonal branch point, suggesting that the branch point is the weakest point in these axons.
Asunto(s)
Potenciales de Acción/fisiología , Axones/fisiología , Corteza Cerebelosa/fisiología , Reflejo H/fisiología , Células de Purkinje/fisiología , Transmisión Sináptica/fisiología , Potenciales de Acción/efectos de los fármacos , Animales , Axones/efectos de los fármacos , Axones/ultraestructura , Bario/farmacología , Cardiotónicos/farmacología , Corteza Cerebelosa/citología , Cesio/farmacología , Electrofisiología/métodos , Femenino , Reflejo H/efectos de los fármacos , Masculino , Fibras Nerviosas Amielínicas/efectos de los fármacos , Fibras Nerviosas Amielínicas/fisiología , Fibras Nerviosas Amielínicas/ultraestructura , Conducción Nerviosa/fisiología , Técnicas de Cultivo de Órganos , Bloqueadores de los Canales de Potasio/farmacología , Canales de Potasio de Rectificación Interna/antagonistas & inhibidores , Canales de Potasio de Rectificación Interna/metabolismo , Células de Purkinje/citología , Células de Purkinje/efectos de los fármacos , Pirimidinas/farmacología , Ratas , Ratas Wistar , Transmisión Sináptica/efectos de los fármacos , TemperaturaRESUMEN
The Common Instrument Middleware Architecture (CIMA) aims at Grid-enabling a wide range of scientific instruments and sensors to enable easy access to and sharing and storage of data produced by these instruments and sensors. This paper describes the implementation of CIMA applied to the field of single-crystal X-ray crystallography. To allow the researchers to easily view the current and past data streams from the instruments or sensors in a laboratory, a crystallography portal and associated portlets were developed for this application. The CIMA-based crystallography system provides an opportunity for anyone with Web access to observe and use crystallographic and other data from laboratories that previously had only limited access.