Complimentary vertebrate Wac models exhibit phenotypes relevant to DeSanto-Shinawi Syndrome.

Monogenic syndromes are associated with neurodevelopmental changes that result in cognitive impairments, neurobehavioral phenotypes including autism and attention deficit hyperactivity disorder (ADHD), and seizures. Limited studies and resources are available to make meaningful headway into the underlying molecular mechanisms that result in these symptoms. One such example is DeSanto-Shinawi Syndrome (DESSH), a rare disorder caused by pathogenic variants in the WAC gene. Individuals with DESSH syndrome exhibit a recognizable craniofacial gestalt, developmental delay/intellectual disability, neurobehavioral symptoms that include autism, ADHD, behavioral difficulties and seizures. However, no thorough studies from a vertebrate model exist to understand how these changes occur. To overcome this, we developed both murine and zebrafish Wac/wac deletion mutants and studied whether their phenotypes recapitulate those described in individuals with DESSH syndrome. We show that the two Wac models exhibit craniofacial and behavioral changes, reminiscent of abnormalities found in DESSH syndrome. In addition, each model revealed impacts to GABAergic neurons and further studies showed that the mouse mutants are susceptible to seizures, changes in brain volumes that are different between sexes and relevant behaviors. Finally, we uncovered transcriptional impacts of Wac loss of function that will pave the way for future molecular studies into DESSH. These studies begin to uncover some biological underpinnings of DESSH syndrome and elucidate the biology of Wac, with advantages in each model.

Comparison of electrochemical nitric oxide detection methods with chemiluminescence for measuring nitrite concentration in food samples.

Nitrite is a naturally occurring species present in various food samples and also present in our bodies as a product of nitric oxide (NO) oxidation. Considering the ubiquity of nitrite, its determination is of great importance in both biological and food samples. Herein, a very facile indirect method of nitrite determination in meat samples via selective reduction to nitric oxide (NO) is presented. The resulting gaseous product is quantified via portable and cost-effective electrochemical sensors. Both a novel laboratory prepared Pt-Nafion based NO sensor and a commercially available amperometric NO sensor are compared. Excellent correlations between the nitrite amount found in tested samples using both of the electrochemical sensors and a reference chemiluminescence method are demonstrated (r = 0.997 and r = 0.999 for Pt-Nafion based and commercially available NO-B4 electrochemical sensors, respectively, n = 12). Moreover, the slope of the linear regression curves are very close to unity for the comparison of the three systems tested. The amperometric sensors compared within this work exhibit good precision and accuracy and are shown to be an attractive alternative to the costly chemiluminescence detection method for accurately determining nitrite levels in food samples.