Articles

Traumatic brain injury (TBI) is one the most common human afflictions, contributing to long-term disability in survivors. Emerging data indicate that functional improvement or deterioration can occur years after TBI. In this regard, TBI is recognized as risk factor for late-life neurodegenerative disorders. TBI encompasses a heterogeneous disease process in which diverse injury subtypes and multiple molecular mechanisms overlap.

In the last couple of years, deep eutectic solvents (DESs) have been raising a lot of attention mainly due to their versatility and their easy and speedy preparation without the need of further purification. Moreover, the vast array of very different compounds that can be selected for their preparation has led to the full tailoring of their relevant properties as solvents.

High-throughput screening for drug discovery is increasingly utilizing cellular systems of high physiological relevance, such as patient primary cells and organoid cultures. We used 3D-cultured cystic fibrosis patient bronchial epithelial cells to screen for new small-molecule correctors of the disease-causing F508del mutation in CFTR. Impaired mucociliary clearance due to insufficient airway hydration is a hallmark of cystic fibrosis and we used a simple measure of surface liquid levels to quantify F508del CFTR correction in cultured bronchial epithelial cells. Two robust assay formats were configured and used to screen more than 100,000 compounds as mixtures or individual compounds in 96-well format. The corrector discovery success rate, as measured by the number of hits confirmed by an electrophysiology assay on patient primary bronchial epithelial cells, was superior to screens in cell lines expressing recombinant F508del CFTR. Several novel corrector scaffolds were discovered that when combined with the clinical corrector VX-809 delivered combination responses greater than double that of VX-809 alone. This work exemplifies the advantages of a disease-relevant readout and 3D-cultured patient primary cells for the discovery of new drug candidates.

Decades of research indicate that the traits we ascribe to people often depend on their race. Yet, the bulk of this research has not considered how racial stereotypes might also depend on other aspects of targets’ identities. To address this, researchers have begun to ask intersectional questions about racial stereotypes, such as whether they are applied in similar ways to men and women, or to children and adults. In the present studies, we examine whether men who are described as gay (vs. not) become de-racialized in the minds of perceivers. That is, we test whether gay (vs.