Vitamin D in the general population of young adults with autism in the Faroe Islands

Vitamin D deficiency has been proposed as a possible risk factor for developing autism spectrum disorder (ASD). 25-Hydroxyvitamin D3 (25(OH)D3) levels were examined in a cross-sectional population-based study in the Faroe Islands. The case group consisting of a total population cohort of 40 individuals with ASD (aged 15–24 years) had significantly lower 25(OH)D3 than their 62 typically-developing siblings and their 77 parents, and also significantly lower than 40 healthy age and gender matched comparisons. There was a trend for males having lower 25(OH)D3 than females. Effects of age, month/season of birth, IQ, various subcategories of ASD and Autism Diagnostic Observation Schedule score were also investigated, however, no association was found. The very low 25(OH)D3 in the ASD group suggests some underlying pathogenic mechanism

Rapid Perturbation in Viremia Levels Drives Increases in Functional Avidity of HIV-specific CD8 T Cells.

The factors determining the functional avidity and its relationship with the broad heterogeneity of antiviral T cell responses remain partially understood. We investigated HIV-specific CD8 T cell responses in 85 patients with primary HIV infection (PHI) or chronic (progressive and non-progressive) infection. The functional avidity of HIV-specific CD8 T cells was not different between patients with progressive and non-progressive chronic infection. However, it was significantly lower in PHI patients at the time of diagnosis of acute infection and after control of virus replication following one year of successful antiretroviral therapy. High-avidity HIV-specific CD8 T cells expressed lower levels of CD27 and CD28 and were enriched in cells with an exhausted phenotype, i.e. co-expressing PD-1/2B4/CD160. Of note, a significant increase in the functional avidity of HIV-specific CD8 T cells occurred in early-treated PHI patients experiencing a virus rebound after spontaneous treatment interruption. This increase in functional avidity was associated with the accumulation of PD-1/2B4/CD160 positive cells, loss of polyfunctionality and increased TCR renewal. The increased TCR renewal may provide the mechanistic basis for the generation of high-avidity HIV-specific CD8 T cells. These results provide insights on the relationships between functional avidity, viremia, T-cell exhaustion and TCR renewal of antiviral CD8 T cell responses

Enhanced tumor cell killing by ultrasound after microtubule depolymerization

Recent studies show that tumor cells are vulnerable to mechanical stresses and undergo calcium‐dependent apoptosis (mechanoptosis) with mechanical perturbation by low‐frequency ultrasound alone. To determine if tumor cells are particularly sensitive to mechanical stress in certain phases of the cell cycle, inhibitors of the cell‐cycle phases are tested for effects on mechanoptosis. Most inhibitors show no significant effect, but inhibitors of mitosis that cause microtubule depolymerization increase the mechanoptosis. Surprisingly, ultrasound treatment also disrupts microtubules independent of inhibitors in tumor cells but not in normal cells. Ultrasound causes calcium entry through mechanosensitive Piezo1 channels that disrupts microtubules via calpain protease activation. Myosin IIA contractility is required for ultrasound‐mediated mechanoptosis and microtubule disruption enhances myosin IIA contractility through activation of GEF‐H1 and RhoA pathway. Further, ultrasound promotes contractility‐dependent Piezo1 expression and localization to the peripheral adhesions where activated Piezo1 allows calcium entry to continue feedback loop. Thus, the synergistic action of ultrasound and nanomolar concentrations of microtubule depolymerizing agents can enhance tumor therapies

Modular Brain Network Organization Predicts Response to Cognitive Training in Older Adults

Cognitive training interventions are a promising approach to mitigate cognitive deficits common in aging and, ultimately, to improve functioning in older adults. Baseline neural factors, such as properties of brain networks, may predict training outcomes and can be used to improve the effectiveness of interventions. Here, we investigated the relationship between baseline brain network modularity, a measure of the segregation of brain sub-networks, and training-related gains in cognition in older adults. We found that older adults with more segregated brain sub-networks (i.e., more modular networks) at baseline exhibited greater training improvements in the ability to synthesize complex information. Further, the relationship between modularity and training-related gains was more pronounced in sub-networks mediating "associative" functions compared with those involved in sensory-motor processing. These results suggest that assessments of brain networks can be used as a biomarker to guide the implementation of cognitive interventions and improve outcomes across individuals. More broadly, these findings also suggest that properties of brain networks may capture individual differences in learning and neuroplasticity. Trail Registration: ClinicalTrials.gov, NCT#00977418