Sleep difficulties are pervasive in autism spectrum disorder (ASD), yet how sleep problems relate to underlying biological mechanisms such as genetic etiology is unclear, despite recent reports of ...profound sleep problems in children with ASD-associated de novo likely gene disrupting (dnLGD) mutations, CHD8, DYRK1A, and ADNP. We aimed to inform etiological contributions to ASD and sleep by characterizing sleep problems in individuals with dnLGD mutations. Participants (N = 2886) were families who completed dichotomous questions about sleep problems within a medical history interview for their child with ASD (age 3-28 years). Confirmatory factor analyses compared between those with ASD and a dnLGD mutation and those with idiopathic ASD (i.e., no known genetic event, NON) highlighted four domains (sleep onset, breathing issues, nighttime awakenings, and daytime tiredness) with sleep onset as a strong factor for both groups. Overall, participant predictors indicated that internalizing behavioral problems and lower cognitive scores were related to increased sleep problems. Internalizing problems were also related to increase nighttime awakenings in the dnLGD group. As an exploratory aim, patterns of sleep issues are described for genetic subgroups with unique patterns including more overall sleep issues in ADNP (n = 19), problems falling asleep in CHD8 (n = 22), and increased daytime naps in DYRK1A (n = 23). Implications for considering genetically defined subgroups when approaching sleep problems in children with ASD are discussed.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A hierarchical model of temporal dynamics was examined in adults (n = 34) and youth (n = 46) across the stages of face processing during the perception of static and dynamic faces. Three ERP ...components (P100, N170, N250) and spectral power in the mu range were extracted, corresponding to cognitive stages of face processing: low-level vision processing, structural encoding, higher-order processing, and action understanding. Youth and adults exhibited similar yet distinct patterns of hierarchical temporal dynamics such that earlier cognitive stages predicted later stages, directly and indirectly. However, latent factors indicated unique profiles related to behavioral performance for adults and youth and age as a continuous factor. The application of path analysis to electrophysiological data can yield novel insights into the cortical dynamics of social information processing.
The polyamines putrescine, spermidine and serine are naturally occurring polycations that are absolutely required for normal cell function, especially in rapidly dividing cells, including parasitic ...organisms. There have been numerous attempts to develop synthetic agents that interrupt polyamine metabolism in mammalian cells, with the underlying theme that disruption of polyamine metabolism could result in targeted cell death. We have extended our work to the development of anti-parasitic agents and anti-neoplastic agents, and have synthesized a series of terminally alkylated polyamine analogues that have specific anti-parasitic and anti-neoplastic activity both in vitro and in vivo. Further, we have used the results of biological studies to refine a set of structure/function correlations. Our analogues have shown structure dependent activity against a number of targets.
Intracellular inclusions composed of hyperphosphorylated filamentous tau are a hallmark of Alzheimer’s disease, progressive supranuclear palsy, Pick’s disease and other sporadic neurodegenerative ...tauopathies. Recent in vitro and in vivo studies have shown that tau aggregates do not only seed further tau aggregation within neurons, but can also spread to neighbouring cells and functionally connected brain regions. This process is referred to as ‘tau propagation’ and may explain the stereotypic progression of tau pathology in the brains of Alzheimer’s disease patients. Here, we describe a novel in vivo model of tau propagation using human P301S tau transgenic mice infused unilaterally with brain extract containing tau aggregates. Infusion-related neurofibrillary tangle pathology was first observed 2 weeks post-infusion and increased in a stereotypic, time-dependent manner. Contralateral and anterior/posterior spread of tau pathology was also evident in nuclei with strong synaptic connections (efferent and afferent) to the site of infusion, indicating that spread was dependent on synaptic connectivity rather than spatial proximity. This notion was further supported by infusion-related tau pathology in white matter tracts that interconnect these regions. The rapid and robust propagation of tau pathology in this model will be valuable for both basic research and the drug discovery process.
Niemann-Pick type C1 (NPC) disease is a lysosomal storage disease caused by mutations in the NPC1 gene, leading to an increase in unesterified cholesterol and several sphingolipids, and resulting in ...hepatic disease and progressive neurological disease. We show that subcutaneous administration of the pharmaceutical excipient 2-hydroxypropyl-β-cyclodextrin (HPβCD) to cats with NPC disease ameliorated hepatic disease, but doses sufficient to reduce neurological disease resulted in pulmonary toxicity. However, direct administration of HPβCD into the cisterna magna of presymptomatic cats with NPC disease prevented the onset of cerebellar dysfunction for greater than a year and resulted in a reduction in Purkinje cell loss and near-normal concentrations of cholesterol and sphingolipids. Moreover, administration of intracisternal HPβCD to NPC cats with ongoing cerebellar dysfunction slowed disease progression, increased survival time, and decreased the accumulation of brain gangliosides. An increase in hearing threshold was identified as a potential adverse effect. These studies in a feline animal model have provided critical data on efficacy and safety of drug administration directly into the central nervous system that will be important for advancing HPβCD into clinical trials.
Urban community gardens provide learning environments for diverse groups, including those who may be experiencing health and social inequalities such as residents in social housing communities. ...Learning to grow fresh food in safe social spaces provides individuals with opportunities to increase awareness of their personal wellbeing and community life. This paper reports on the findings of a research study that explored broader impacts of a community gardening programme on 42 adult residents living in social housing estates in Sydney, Australia. The mixed-methods study design captured participants' self-perceived benefits of community gardening across six new sites. A final sample of 23 participants across the sites completed both the Sense of Community Index 2 and the Personal Wellbeing Index questionnaires at pre- and post-test (following six to seven months of being involved in the programme). Focus groups involved 42 participants from all six sites. Perceived benefits included enhanced awareness of their overall health and wellbeing, new interest in growing fresh food, enjoyment of shared produce and recipes, feelings of happiness, frequent socialisation and community connectedness. The findings highlight the impactful role of community gardens as effective local learning environments that promote psychological wellbeing and community connection in underserved communities. We conclude by reinforcing the need for sustainable community gardens for addressing social inequality and promoting multiple psychosocial benefits.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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