Shared and Distinct Functional Effects of Patient-Specific Mutations on Cortical Development.

T-Box Brain Transcription Factor 1 (TBR1) plays essential roles in brain development, mediating neuronal migration, fate specification, and axon tract formation. While heterozygous loss-of-function and missense mutations are associated with neurodevelopmental conditions, the effects of these heterogeneous mutations on brain development have yet to be fully explored. We characterized multiple mouse lines carrying mutations differing by type and exonic location, including the previously generated exon 2-3 knock-out (KO) line, and we analyzed male and female mice at neonatal and adult stages.

Invasion of the body snatchers: the role of parasite introduction in host distribution and response to salinity in invaded estuaries.

In dynamic systems, organisms are faced with variable selective forces that may impose trade-offs. In estuaries, salinity is a strong driver of organismal diversity, while parasites shape species distributions and demography. We tested for trade-offs between low-salinity stress and parasitism in an invasive castrating parasite and its mud crab host along salinity gradients of two North Carolina rivers.

Autism and attention-deficit/hyperactivity disorders and symptoms in children with neurofibromatosis type 1.

Aim: To evaluate if autism symptoms and diagnoses are more common in children with neurofibromatosis type 1 (NF1) than in typically developing children, to which levels, and to determine if co-occurring attention-deficit/hyperactivity disorder (ADHD) symptomatology accounts for this increase.

Method: We searched hospital electronic medical records (EMR) for International Classification of Diseases, 10th Revision NF1 and co-occurring diagnoses codes. We recruited a subsample of 45 children (mean age 9y 2mo; SD 2y 7mo; range 5-12y; 22 males, 23 females) and collected parental reports of autism symptomatology, adaptive behavior, and behavioral problems that were compared to those of 360 age- and sex-matched controls from the Simons Simplex Collection (SSC) with autism spectrum disorder (ASD; SSC-ASD) or typically developing (SSC-TD).

Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes.

Autism spectrum disorder (ASD) is a genetically heterogeneous condition, caused by a combination of rare de novo and inherited variants as well as common variants in at least several hundred genes. However, significantly larger sample sizes are needed to identify the complete set of genetic risk factors. We conducted a pilot study for SPARK (SPARKForAutism.

Collecting Symptoms and Sensor Data With Consumer Smartwatches (the Knee OsteoArthritis, Linking Activity and Pain Study): Protocol for a Longitudinal, Observational Feasibility Study.

Background: The Knee OsteoArthritis, Linking Activity and Pain (KOALAP) study is the first to test the feasibility of using consumer-grade cellular smartwatches for health care research.

Objective: The overall aim was to investigate the feasibility of using consumer-grade cellular smartwatches as a novel tool to capture data on pain (multiple times a day) and physical activity (continuously) in patients with knee osteoarthritis. Additionally, KOALAP aimed to investigate smartwatch sensor data quality and assess whether engagement, acceptability, and user experience are sufficient for future large-scale observational and interventional studies.

Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder.

Genetic risk factors for autism spectrum disorder (ASD) have yet to be fully elucidated. Postzygotic mosaic mutations (PMMs) have been implicated in several neurodevelopmental disorders and overgrowth syndromes. By leveraging whole-exome sequencing data on a large family-based ASD cohort, the Simons Simplex Collection, we systematically evaluated the potential role of PMMs in autism risk.

Autophagy Inhibition Delays Early but Not Late-Stage Metastatic Disease.

The autophagy pathway has been recognized as a mechanism of survival and therapy resistance in cancer, yet the extent of autophagy's function in metastatic progression is still unclear. Therefore, we used murine models of metastatic cancer to investigate the effect of autophagy modulation on metastasis development. Pharmacologic and genetic autophagy inhibition were able to impede cell proliferation in culture, but did not impact the development of experimentally induced 4T1 and B16-F10 metastases.

Mutations and Modeling of the Chromatin Remodeler CHD8 Define an Emerging Autism Etiology.

Autism Spectrum Disorder (ASD) is a common neurodevelopmental disorder with a strong but complex genetic component. Recent family based exome-sequencing strategies have identified recurrent de novo mutations at specific genes, providing strong evidence for ASD risk, but also highlighting the extreme genetic heterogeneity of the disorder. However, disruptions in these genes converge on key molecular pathways early in development.

Phase I clinical trial and pharmacodynamic evaluation of combination hydroxychloroquine and doxorubicin treatment in pet dogs treated for spontaneously occurring lymphoma.

Autophagy is a lysosomal degradation process that may act as a mechanism of survival in a variety of cancers. While pharmacologic inhibition of autophagy with hydroxychloroquine (HCQ) is currently being explored in human clinical trials, it has never been evaluated in canine cancers. Non-Hodgkin lymphoma (NHL) is one of the most prevalent tumor types in dogs and has similar pathogenesis and response to treatment as human NHL.

STAT3-mediated autophagy dependence identifies subtypes of breast cancer where autophagy inhibition can be efficacious.

Autophagy is a protein and organelle degradation pathway that is involved in diverse diseases, including cancer. Recent evidence suggests that autophagy is a cell survival mechanism in tumor cells and that its inhibition, especially in combination with other therapy, could be beneficial but it remains unclear if all cancer cells behave the same way when autophagy is inhibited. We inhibited autophagy in a panel of breast cancer cell lines and found that some of them are dependent on autophagy for survival even in nutrient rich conditions without any additional stress, whereas others need autophagy only when stressed.