Traumatic stress-enhanced ethanol drinking: Sex, but not stress responsivity, alters sensitivity to the effects of a CRF-R1 antagonist and a GPR39 agonist in mice.

Background: Predator stress (PS) is used to model trauma leading to post-traumatic stress disorder, and it increases ethanol drinking in a proportion of male and female rodents. The goals of the present studies were to identify male and female mice with prior binge drinking experience that exhibited sensitivity and resilience to PS-enhanced drinking and then to test two target molecules (corticotropin releasing factor receptor 1 [CRF-R1] antagonist NBI-27914 [NBI] and G-protein coupled receptor 39 [GPR39] agonist TC-G 1008 [TC-G]) for their ability to selectively reduce PS-enhanced drinking.

Methods: Adult male and female C57BL/6J mice received seven binge ethanol sessions, a period of abstinence, and acclimation to lickometer chambers to examine the effects of NBI or TC-G on stress-associated drinking.

Dopamine loss alters glutamate synapses and transporters in the medial prefrontal cortex and anxiety-related behaviour in a male MPTP rodent model of Parkinson's disease.

Anxiety is a prominent non-motor symptom of Parkinson's disease (PD). Changes in the B-spectrum recordings in PD patients of the prefrontal cortex correlate with increased anxiety. Using a rodent model of PD, we reported alterations in glutamate synapses in the striatum and substantia nigra following dopamine (DA) loss.

Hippo pathway-mediated YAP1/TAZ inhibition is essential for proper pancreatic endocrine specification and differentiation.

The Hippo pathway plays a central role in tissue development and homeostasis. However, the function of Hippo in pancreatic endocrine development remains obscure. Here, we generated novel conditional genetically engineered mouse models to examine the roles of Hippo pathway-mediated YAP1/TAZ inhibition in the development stages of endocrine specification and differentiation.

Reconstitution of human PDAC using primary cells reveals oncogenic transcriptomic features at tumor onset.

Animal studies have demonstrated the ability of pancreatic acinar cells to transform into pancreatic ductal adenocarcinoma (PDAC). However, the tumorigenic potential of human pancreatic acinar cells remains under debate. To address this gap in knowledge, we expand sorted human acinar cells as 3D organoids and genetically modify them through introduction of common PDAC mutations.

TGFβ and Hippo Signaling Pathways Coordinate to Promote Acinar to Ductal Metaplasia in Human Pancreas.

Background & Aims: Acinar-to-ductal metaplasia (ADM) serves as a precursor event in the development of pancreatic ductal adenocarcinoma (PDAC) upon constitutive environmental and genetical stress. While the role of ADM in PDAC progression has been established, the molecular mechanisms underlying human ADM remain elusive. We previously demonstrated the induction of ADM in human acinar cells through the transforming growth factor beta (TGFβ) signaling pathway.