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Chromatin dynamics are mediated by remodeling enzymes and play crucial roles in gene regulation, as established in a paradigmatic model, the Saccharomyces cerevisiae PHO5 promoter. However, effective nucleosome dynamics, that is, trajectories of promoter nucleosome configurations, remain elusive. Here, we infer such dynamics from the integration of published single-molecule data capturing multi-nucleosome configurations for repressed to fully active PHO5 promoter states with other existing histone turnover and new chromatin accessibility data. https://www.selleckchem.com/products/vorolanib.html We devised and systematically investigated a new class of 'regulated on-off-slide' models simulating global and local nucleosome (dis)assembly and sliding. Only seven of 68,145 models agreed well with all data. All seven models involve sliding and the known central role of the N-2 nucleosome, but regulate promoter state transitions by modulating just one assembly rather than disassembly process. This is consistent with but challenges common interpretations of previous observations at the PHO5 promoter and suggests chromatin opening by binding competition.Transmembrane protein Golden goal (Gogo) interacts with atypical cadherin Flamingo (Fmi) to direct R8 photoreceptor axons in the Drosophila visual system. However, the precise mechanisms underlying Gogo regulation during columnar- and layer-specific R8 axon targeting are unknown. Our studies demonstrated that the insulin secreted from surface and cortex glia switches the phosphorylation status of Gogo, thereby regulating its two distinct functions. Non-phosphorylated Gogo mediates the initial recognition of the glial protrusion in the center of the medulla column, whereas phosphorylated Gogo suppresses radial filopodia extension by counteracting Flamingo to maintain a one axon-to-one column ratio. Later, Gogo expression ceases during the midpupal stage, thus allowing R8 filopodia to extend vertically into the M3 layer. These results demonstrate that the long- and short-range signaling between the glia and R8 axon growth cones regulates growth cone dynamics in a stepwise manner, and thus shapes the entire organization of the visual system.Establishing how many people have been infected by SARS-CoV-2 remains an urgent priority for controlling the COVID-19 pandemic. Serological tests that identify past infection can be used to estimate cumulative incidence, but the relative accuracy and robustness of various sampling strategies have been unclear. We developed a flexible framework that integrates uncertainty from test characteristics, sample size, and heterogeneity in seroprevalence across subpopulations to compare estimates from sampling schemes. Using the same framework and making the assumption that seropositivity indicates immune protection, we propagated estimates and uncertainty through dynamical models to assess uncertainty in the epidemiological parameters needed to evaluate public health interventions and found that sampling schemes informed by demographics and contact networks outperform uniform sampling. The framework can be adapted to optimize serosurvey design given test characteristics and capacity, population demography, sampling strategy, and modeling approach, and can be tailored to support decision-making around introducing or removing interventions. The COVID-19 pandemic has challenged the population of affected areas in multiple dimensions. Adolescents have been especially affected with school closure and home confinement. The impact of the pandemic on sleep habits and quality of sleep and quality of life among adolescents have not been adequately characterized. We hypothesized that the COVID-19 pandemic induced an evening shift of the daily rhythm among adolescents and adversely affected sleep quality and quality of life of high school students. Students were questioned about their usual bed and wake-up times and answered the Pittsburg Sleep Quality Index Questionnaire (PSQI), the Epworth Sleepiness Scale (ESS), the Morning-Eveningness Questionnaire (MEQ) and the World Health Organization Quality of Life Questionnaire (WHOQOL) before and during the pandemic. Ninety-four students (64% females, aged 15+1 years) participated in both phases of the study. Students delayed bed and wake-up times in 1.5[0.5-2.0] and 2.0[1.5-2.5]h, respectively. Chronotypandemic. Narcolepsy type 1 (NT1) is a chronic neurological disorder typically arising during adolescence and young adulthood. Recent studies demonstrated that NT1 presents with age-specific features, especially in children. With this study we aimed to describe and to compare the clinical pictures of NT1 in different age groups. In this cross-sectional, multicenter study, 106 untreated NT1 patients, enrolled at the time of diagnosis, underwent clinical evaluation, a semi-structured interview (including the Epworth Sleepiness Scale - ESS), nocturnal video-polysomnography and the Multiple Sleep Latency Test (MSLT). Patients were enrolled in order to establish five age-balanced groups (childhood, adolescence, adulthood, middle-aged and seniors). The ESS score showed a significant increase with age, while self-reported diurnal total sleep time was lower in elderly and young adults, with the latter also complaining of automatic behaviors in more than 90% of cases. Children reported the cataplexy attacks to be more frequent (&gt;1/day in 95% of cases). "Recalling an emotional event", "meeting someone unexpectedly", "stress" and "anger" were more frequently reported in adult and elderly patients as possible triggers of cataplexy. Neurophysiological data showed a higher number of SOREMPs on the MSLT in adolescents compared to senior patients and an age-progressive decline in sleep efficiency. Daytime sleepiness, cataplexy features and triggers, and nocturnal sleep structure showed age-related difference in NT1 patients; this variability may contribute to diagnostic delay and misdiagnosis.Daytime sleepiness, cataplexy features and triggers, and nocturnal sleep structure showed age-related difference in NT1 patients; this variability may contribute to diagnostic delay and misdiagnosis.

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