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Synaptic activity in neurons leads to the rapid activation of genes involved in mammalian behavior. ATP-dependent chromatin remodelers such as the BAF complex contribute to these responses and are generally thought to activate transcription. However, the mechanisms keeping such "early activation" genes silent have been a mystery. In the course of investigating Mendelian recessive autism, we identified six families with segregating loss-of-function mutations in the neuronal BAF (nBAF) subunit ACTL6B (originally named BAF53b). Accordingly, ACTL6B was the most significantly mutated gene in the Simons Recessive Autism Cohort. At least 14 subunits of the nBAF complex are mutated in autism, collectively making it a major contributor to autism spectrum disorder (ASD). Patient mutations destabilized ACTL6B protein in neurons and rerouted dendrites to the wrong glomerulus in the fly olfactory system. Humans and mice lacking ACTL6B showed corpus callosum hypoplasia, indicating a conserved role for ACTL6B in facilitating neural connectivity. Actl6b knockout mice on two genetic backgrounds exhibited ASD-related behaviors, including social and memory impairments, repetitive behaviors, and hyperactivity. Surprisingly, mutation of Actl6b relieved repression of early response genes including AP1 transcription factors (Fos, Fosl2, Fosb, and Junb), increased chromatin accessibility at AP1 binding sites, and transcriptional changes in late response genes associated with early response transcription factor activity. ACTL6B loss is thus an important cause of recessive ASD, with impaired neuron-specific chromatin repression indicated as a potential mechanism.

Aim: With the outbreak of COVID‐19 and associated challenges such as increased workload for health providers and shortage of equipment, it became more challenging to maintain patients' dignity and satisfaction. This study evaluated the patients' dignity and satisfaction with COVID‐19 in Kashan, Iran, in 2021. Design: A cross‐sectional descriptive study. Methods: In total, 385 patients recovered from COVID‐19 were selected through sequential sampling method. Data were collected using demographic, patient dignity inventory, and patient satisfaction questionnaires. Data were analysed using descriptive analysis, independent t‐test, ANOVA, and Spearman‐Brown coefficient. Results: The mean age of patients was 50.57. The mean scores of patients' dignity and satisfaction were 1.622 ± 0.653 and 3.851 ± 0.548 (out of 5), respectively. The dignity rating was associated with age, gender, education, underlying disease, and length of hospital stay (p < 0.05); but patient satisfaction was only associated with education (p = 0.002). The results indicated that dignity and satisfaction have a significant direct correlation (r = −0.23, p < 0.001). Patient or Public Contribution: This study was designed based on the research priorities and needs in the field of clinical research and patients were involved in conducting the study via participating in data collection. [ABSTRACT FROM AUTHOR]

In the plane, the winding number is the number of times a curve wraps around a given point. Winding numbers are a basic component of geometric algorithms such as point-in-polygon tests, and their generalization to data with noise or topological errors has proven valuable for geometry processing tasks ranging from surface reconstruction to mesh booleans. However, standard definitions do not immediately apply on surfaces, where not all curves bound regions. We develop a meaningful generalization, starting with the well-known relationship between winding numbers and harmonic functions. By processing the derivatives of such functions, we can robustly filter out components of the input that do not bound any region. Ultimately, our algorithm yields (i) a closed, completed version of the input curves, (ii) integer labels for regions that are meaningfully bounded by these curves, and (iii) the complementary curves that do not bound any region. The main computational cost is solving a standard Poisson equation, or for surfaces with nontrivial topology, a sparse linear program. We also introduce special basis functions to represent singularities that naturally occur at endpoints of open curves. [ABSTRACT FROM AUTHOR]

There is considerable concern over declines in insect pollinator communities and potential impacts on the pollination of crops and wildflowers (1-4). Among the multiple pressures facing pollinators (2-4), decreasing floral [...]