SUMMARY FOG-2 is a multi-zinc finger protein that binds the transcriptional activator GATA4 and modulates GATA4-mediated regulation of target genes during heart development. Our previous work has demonstrated that the Nucleosome Remodeling and Deacetylase (NuRD) complex physically interacts with FOG-2 and is necessary for FOG-2 mediated repression of GATA4 activity in vitro. However, the relevance of this interaction for FOG-2 function in vivo has remained unclear. In this report, we demonstrate the importance of FOG-2/NuRD interaction through the generation and characterization of mice homozygous for a mutation in FOG-2 that disrupts NuRD binding (FOG-2R3K5A). These mice exhibit a perinatal lethality and have multiple cardiac malformations, including ventricular and atrial septal defects and a thin ventricular myocardium. To investigate the etiology of the thin myocardium, we measured the rate of cardiomyocyte proliferation in wild-type and FOG-2R3K5A developing hearts. We found cardiomyocyte proliferation was reduced by 31 ± 8% in FOG-2R3K5A mice. Gene expression analysis indicated that the cell cycle inhibitor Cdkn1a (p21cip1) is up-regulated 2.0 ± 0.2-fold in FOG-2R3K5A hearts. In addition, we demonstrate that FOG-2 can directly repress the activity of the Cdkn1a gene promoter, suggesting a model by which FOG-2/NuRD promotes ventricular wall thickening by repression of this cell cycle inhibitor. Consistent with this notion, the genetic ablation of Cdkn1a in FOG-2R3K5A mice leads to an improvement in left ventricular function and a partial rescue of left ventricular wall thickness. Taken together, our results define a novel mechanism in which FOG-2/NuRD interaction is required for cardiomyocyte proliferation by directly down-regulating the cell cycle inhibitor Cdkn1a during heart development.

No abstract

No abstract

Iatrogenic complications can result from both diagnostic and therapeutic hepatobiliary interventions such as percutaneous transhepatic cholangiography, percutaneous biliary drain placement, percutaneous liver biopsy, transarterial liver-directed therapies for malignancy, and liver transplantation. In many of these procedures, the proximity of the biliary ductal system to the hepatic arteries and portal veins predisposes to injury. In other procedures, compromised arterial supply to the biliary system, errors related to complexity of the procedures, or the fragility of the structures themselves may be the root cause. Understanding the etiology of these iatrogenic complications as well as the management options is essential for a multidisciplinary team tasked with managing patients with complex hepatobiliary diseases.

We created an interactive application Learn Radiology with multi-parametric MRI - whole mount histology correlation for enhanced prostate MRI training of radiologists and validated whether the use of a newly created learning application can enhance prostate MRI training of radiologists using an observer study. Sensitivity (R1: 54%→64%, R2: 44%→59%, R3: 62%→72%), PPV (R1: 68%→76%, R2: 52%→79%, R3: 48%→65%) and confidence score (R1: 4.0±1.0→4.3±0.8, R2: 3.1±0.8→4.0±1.1, R3: 2.8±1.2→4.1±1.1, p<0.05) for prostate cancer diagnosis using mpMRI improved for all three radiologists along with inter-observer agreement (α 0.78→0.85) after being exposed to our developed teaching app.