RESUMO
We developed an iOS-based app with a transmitter/disposable sensor and corresponding manualized intervention for children with autism spectrum disorder. The app signaled the onset of urination, time-stamped accidents for analysis, reminded parents to reinforce intervals of continence, provided a visual outlet for parents to communicate reinforcement, and afforded opportunity for timely feedback from clinicians. We compared this intervention with an intervention that uses standard behavioral treatment in a pilot randomized controlled trial of 33 children with autism spectrum disorder aged 3-6 years with urinary incontinence. Parents in both groups received initial training and four booster consultations over 3 months. Results support the feasibility of parent-mediated toilet training studies (e.g., 84% retention rate, 92% fidelity of parent-implemented intervention). Parents used the app and related technology with few difficulties or malfunctions. There were no statistically significant group differences for rate of urine accidents, toilet usage, or satisfaction at close of intervention or 3-month follow-up; however, the alarm group trended toward greater rate of skill acquisition with significantly less day-to-day intervention. Further development of alarm and related technology and future comparative studies with a greater number of participants are warranted.
Assuntos
Transtorno do Espectro Autista/reabilitação , Enurese/reabilitação , Aplicativos Móveis , Pais , Treinamento no Uso de Banheiro , Criança , Pré-Escolar , Estudos de Viabilidade , Feminino , Humanos , Masculino , Projetos Piloto , Reforço Psicológico , Tecnologia sem FioRESUMO
Regions of highly repetitive DNA, such as those found in the nucleolus, show a self-organization that is marked by spatial segregation and frequent self-interaction. The mechanisms that underlie the sequestration of these sub-domains are largely unknown. Using a stochastic, bead-spring representation of chromatin in budding yeast, we find enrichment of protein-mediated, dynamic chromosomal cross-links recapitulates the segregation, morphology and self-interaction of the nucleolus. Rates and enrichment of dynamic crosslinking have profound consequences on domain morphology. Our model demonstrates the nucleolus is phase separated from other chromatin in the nucleus and predicts that multiple rDNA loci will form a single nucleolus independent of their location within the genome. Fluorescent labeling of budding yeast nucleoli with CDC14-GFP revealed that a split rDNA locus indeed forms a single nucleolus. We propose that nuclear sub-domains, such as the nucleolus, result from phase separations within the nucleus, which are driven by the enrichment of protein-mediated, dynamic chromosomal crosslinks.
Assuntos
Nucléolo Celular/genética , Cromossomos Fúngicos/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Algoritmos , Nucléolo Celular/metabolismo , Núcleo Celular/genética , Núcleo Celular/metabolismo , Segregação de Cromossomos , Cinética , Modelos Genéticos , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMO
Chromatin exhibits increased mobility on DNA damage, but the biophysical basis for this behavior remains unknown. To explore the mechanisms that drive DNA damage-induced chromosome mobility, we use single-particle tracking of tagged chromosomal loci during interphase in live yeast cells together with polymer models of chromatin chains. Telomeres become mobilized from sites on the nuclear envelope and the pericentromere expands after exposure to DNA-damaging agents. The magnitude of chromatin mobility induced by a single double-strand break requires active microtubule function. These findings reveal how relaxation of external tethers to the nuclear envelope and internal chromatin-chromatin tethers, together with microtubule dynamics, can mobilize the genome in response to DNA damage.
