Valvular heart disease presents a significant health burden, yet advancements in valve biology and therapeutics have been hindered by the lack of accessibility to human valve cells. In this study, we have developed a scalable and feeder-free method to differentiate human induced pluripotent stem cells (iPSCs) into endocardial cells, which are transcriptionally and phenotypically distinct from vascular endothelial cells. These endocardial cells can be challenged to undergo endothelial-to-mesenchymal transition (EndMT), after which two distinct populations emerge-one population undergoes EndMT to become valvular interstitial cells (VICs), while the other population reinforces their endothelial identity to become valvular endothelial cells (VECs).
View Article and Find Full Text PDFLesbian, gay, bisexual, transgender, queer/questioning, and other sexual and gender minority (LGBTQ+) asylum seekers are exposed to high rates of persecution. This study aimed to identify the forms of ill treatment and the impact of these experiences on the mental health of 66 self-identified LGBTQ+ asylum seekers from 24 nations through the analysis of human rights program intakes, sworn declarations, and pro bono forensic psychological evaluation affidavits. The results indicate that participants experienced physical assault (92.
View Article and Find Full Text PDFThe COVID-19 pandemic has resulted in an alarming increase in hate incidents directed toward Asian Americans and Pacific Islanders (AAPIs), including verbal harassment and physical assault, spurring the nationwide #StopAsianHate movement. This rise in anti-Asian sentiment is occurring at a critical time of racial reckoning across the United States, galvanized by the Black Lives Matter movement, and of medical student calls for the implementation of antiracist medical curricula. AAPIs are stereotyped by the model minority myth, which posits that AAPIs are educated, hardworking, and therefore able to achieve high levels of success.
View Article and Find Full Text PDFα7 nicotinic acetylcholine receptors (nAChRs) are widely expressed in the brain where they promote fast cholinergic synaptic transmission and serve important neuromodulatory functions. However, their high permeability to Ca also predisposes them to contribute to disease states. Here, using transfected HEK-tsa cells and primary cultured hippocampal neurons from male and female rats, we demonstrate that two proteins called Ly6h and NACHO compete for access to α7 subunits, operating together but in opposition to maintain α7 assembly and activity within a narrow range that is optimal for neuronal function and viability.
View Article and Find Full Text PDFLy6 proteins are endogenous prototoxins found in most animals. They show striking structural and functional parallels to snake α-neurotoxins, including regulation of ion channels and cholinergic signaling. However, the structural contributions of Ly6 proteins to regulation of effector molecules is poorly understood.
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