Raising Children on the Autism Spectrum: Parental Needs

The rates of Autism Spectrum Disorder (ASD) diagnoses have increased rapidly in the past few years. This increase is affecting many American families but the current research literature fails to evaluate the needs of parents who are raising children on the spectrum. Parents of children with Autism experience grief, denial, anger, guilt, depression, isolation, stress, financial difficulties, and marital struggles. The author proposed a mixed methods study to determine services received and satisfaction with those services; level of parental interest in specialized services; how well parents’ needs had been met with existing services; and what services parents of autistic children find they need the most. To answer these questions, parents of children on the autism spectrum were asked to complete a questionnaire about their interests, needs and the usefulness of existing services

Activation of GSK-3 and phosphorylation of CRMP2 in transgenic mice expressing APP intracellular domain

Amyloid precursor protein (APP), implicated in Alzheimer's disease, is a trans-membrane protein of undetermined function. APP is cleaved by γ-secretase that releases the APP intracellular domain (AICD) in the cytoplasm. In vitro studies have implicated AICD in cell signaling and transcriptional regulation, but its biologic relevance has been uncertain and its in vivo function has not been examined. To investigate its functional role, we generated AICD transgenic mice, and found that AICD causes significant biologic changes in vivo. AICD transgenic mice show activation of glycogen synthase kinase-3β (GSK-3β) and phosphorylation of CRMP2 protein, a GSK-3β substrate that plays a crucial role in Semaphorin3a-mediated axonal guidance. Our data suggest that AICD is biologically relevant, causes significant alterations in cell signaling, and may play a role in axonal elongation or pathfinding

Single-Cell Transcriptomes Reveal a Complex Cellular Landscape in the Middle Ear and Differential Capacities for Acute Response to Infection.

Single-cell transcriptomics was used to profile cells of the normal murine middle ear. Clustering analysis of 6770 transcriptomes identified 17 cell clusters corresponding to distinct cell types: five epithelial, three stromal, three lymphocyte, two monocyte, two endothelial, one pericyte and one melanocyte cluster. Within some clusters, cell subtypes were identified. While many corresponded to those cell types known from prior studies, several novel types or subtypes were noted. The results indicate unexpected cellular diversity within the resting middle ear mucosa. The resolution of uncomplicated, acute, otitis media is too rapid for cognate immunity to play a major role. Thus innate immunity is likely responsible for normal recovery from middle ear infection. The need for rapid response to pathogens suggests that innate immune genes may be constitutively expressed by middle ear cells. We therefore assessed expression of innate immune genes across all cell types, to evaluate potential for rapid responses to middle ear infection. Resident monocytes/macrophages expressed the most such genes, including pathogen receptors, cytokines, chemokines and chemokine receptors. Other cell types displayed distinct innate immune gene profiles. Epithelial cells preferentially expressed pathogen receptors, bactericidal peptides and mucins. Stromal and endothelial cells expressed pathogen receptors. Pericytes expressed pro-inflammatory cytokines. Lymphocytes expressed chemokine receptors and antimicrobials. The results suggest that tissue monocytes, including macrophages, are the master regulators of the immediate middle ear response to infection, but that virtually all cell types act in concert to mount a defense against pathogens

Late Jurassic Paleogeography of the U.S. Cordillera from Detrital Zircon Age and Hafnium Analysis of the Galice Formation, Klamath Mountains, Oregon and California, USA

The Upper Jurassic Galice Formation, a metasedimentary unit in the Western Klamath Mountains, formed within an intra-arc basin prior to and during the Nevadan orogeny. New detrital zircon U-Pb age analyses (N = 11; n = 2792) yield maximum depositional ages (MDA) ranging from ca. 160 Ma to 151 Ma, which span Oxfordian to Kimmeridgian time and overlap Nevadan contractional deformation that began by ca. 157 Ma. Zircon ages indicate a significant North American continental provenance component that is consistent with tectonic models placing the Western Klamath terrane on the continental margin in Late Jurassic time. Hf isotopic analysis of Mesozoic detrital zircon (n = 603) from Galice samples reveals wide-ranging εHf values for Jurassic and Triassic grains, many of which cannot be explained by a proximal source in the Klamath Mountains, thus indicating a complex provenance. New U-Pb ages and Hf data from Jurassic plutons within the Klamath Mountains match some of the Galice Formation detrital zircon, but these data cannot account for the most non-radiogenic Jurassic detrital grains. In fact, the in situ Cordilleran arc record does not provide a clear match for the wide-ranging isotopic signature of Triassic and Jurassic grains. When compiled, Galice samples indicate sources in the Sierra Nevada pre-batholithic framework and retroarc region, older Klamath terranes, and possibly overlap strata from the Blue Mountains and the Insular superterrane. Detrital zircon age spectra from strata of the Upper Jurassic Great Valley Group and Mariposa Formation contain similar age modes, which suggests shared sediment sources. Inferred Galice provenance within the Klamath Mountains and more distal sources suggest that the Galice basin received siliciclastic turbidites fed by rivers that traversed the Klamath-Sierran arc from headwaters in the retroarc region. Thus, the Galice Formation contains a record of active Jurassic magmatism in the continental arc, with significant detrital input from continental sediment sources within and east of the active arc. These westward-flowing river systems remained active throughout the shift in Cordilleran arc tectonics from a transtensional system to the Nevadan contractional system, which is characterized by sediment sourced in uplifts within and east of the arc and the thrusting of older Galice sediments beneath older Klamath terranes to the east

Evidence that BDNF regulates heart rate by a mechanism involving increased brainstem parasympathetic neuron excitability

Autonomic control of heart rate is mediated by cardioinhibitory parasympathetic cholinergic neurons located in the brainstem and stimulatory sympathetic noradrenergic neurons. During embryonic development the survival and cholinergic phenotype of brainstem autonomic neurons is promoted by brain-derived neurotrophic factor (BDNF). We now provide evidence that BDNF regulates heart rate by a mechanism involving increased brainstem cardioinhibitory parasympathetic activity. Mice with a BDNF haploinsufficiency exhibit elevated resting heart rate, and infusion of BDNF intracerebroventricularly reduces heart rate in both wild-type and BDNF+/− mice. The atropine-induced elevation of heart rate is diminished in BDNF+/− mice and is restored by BDNF infusion, whereas the atenolol-induced decrease in heart rate is unaffected by BDNF levels, suggesting that BDNF signaling enhances parasympathetic tone which is diminished with BDNF haploinsufficiency. Whole-cell recordings from pre-motor cholinergic cardioinhibitory vagal neurons in the nucleus ambiguus indicate that BDNF haploinsufficiency reduces cardioinhibitory vagal neuron activity by increased inhibitory GABAergic and diminished excitatory glutamatergic neurotransmission to these neurons. Our findings reveal a previously unknown role for BDNF in the control of heart rate by a mechanism involving increased activation of brainstem cholinergic parasympathetic neurons Mice with reduced BDNF levels exhibit elevated heart rate, and infusion of BDNF into the brain normalizes heart rate by a mechanism involving increased brainstem cardioinhibitory parasympathetic activity. Recordings from pre-motor cholinergic cardioinhibitory vagal neurons (CVNs) in the nucleus ambiguus indicate that BDNF increases CVN activity by increasing excitatory glutamatergic and decreasing inhibitory GABAergic neurotransmission to these neurons. Perhaps factors that increase parasympathetic tone (e.g., exercise) reduce resting heart rate, in part, by a BDNF-mediated mechanism

The Firebreak Problem

Suppose we have a network that is represented by a graph $G$. Potentially a fire (or other type of contagion) might erupt at some vertex of $G$. We are able to respond to this outbreak by establishing a firebreak at $k$ other vertices of $G$, so that the fire cannot pass through these fortified vertices. The question that now arises is which $k$ vertices will result in the greatest number of vertices being saved from the fire, assuming that the fire will spread to every vertex that is not fully behind the $k$ vertices of the firebreak. This is the essence of the {\sc Firebreak} decision problem, which is the focus of this paper. We establish that the problem is intractable on the class of split graphs as well as on the class of bipartite graphs, but can be solved in linear time when restricted to graphs having constant-bounded treewidth, or in polynomial time when restricted to intersection graphs. We also consider some closely related problems

Population sequencing data reveal a compendium of mutational processes in human germline

Mechanistic processes underlying human germline mutations remain largely unknown.Variation in mutation rate and spectra along the genome is informative about the biological mechanisms. We statistically decompose this variation into separate processes using a blind source separation technique. The analysis of a large-scale whole genome sequencing dataset (TOPMed) reveals nine processes that explain the variation in mutation properties between loci. Seven of these processes lend themselves to a biological interpretation. One process is driven by bulky DNA lesions that resolve asymmetrically with respect to transcription and replication. Two processes independently track direction of replication fork and replication timing. We identify a mutagenic effect of active demethylation primarily acting in regulatory regions. We also demonstrate that a recently discovered mutagenic process specific to oocytes can be localized solely from population sequencing data. This process is spread across all chromosomes and is highly asymmetric with respect to the direction of transcription, suggesting a major role of DNA damage

Adolescents' understanding of obesity: a qualitative study from rural South Africa.

Funder: Department of HealthBACKGROUND: Levels of obesity are rising in South Africa, notably among adolescent females. Excessive energy-dense diets and physical inactivity are among the factors contributing to this increase. Given that these factors are largely behavioural, understanding young people's views of obesity can contribute to more targeted behavioural interventions. Yet little is known of how rural South African adolescents view obesity. OBJECTIVES: The aim of this study was to explore rural South African adolescents' views of obesity, including their understanding of its causes, consequences, and solutions. METHODS: This qualitative study took place within the MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt) study area, in rural northeast South Africa. Three focus group discussions were held with male (n = 16) and female adolescents (n = 15), aged 14-19 years in 2018. Data were analysed using thematic analysis and the Social Cognitive Theory used to frame the findings. RESULTS: Participants presented conflicting views of obesity, with both positive and negative opinions expressed. Causes of obesity were seen to be multifactorial, including genetics, diet, lack of physical activity, and HIV treatment. Adolescents proposed medication and hospitalisation as ways to address obesity. When discussing interventions to address obesity, adolescents expressed the need for more information, suggesting that providing information to both themselves and their family members as part of interventions would be important. CONCLUSIONS: Rural South African adolescents have a complex perspective of obesity, likely driven in part by the current nutrition transition underway and do not inherently see individual behaviour as a driver or mitigator of obesity. Complex interventions including the involvement of other household members are needed to change adolescents' views on the role of the individual, and ultimately, change both individual and household behaviour to prevent obesity