Implementation of an Active Screening Program for SARS-CoV2 - Experience at an Academic Medical Center.

BACKGROUND: This study documents the experience of an academic medical center implementing SARS-CoV2 screening of asymptomatic research personnel to support the "return-to-work" initiative and donor cadavers to support in-person student education. METHODS: Testing was performed on samples received June 1, 2020 (for the cadaver program) and July 20, 2020 (for the personnel screening program) through September 30, 2021. Data were evaluated to document the number of cases and the positivity rate. RESULTS: Approximately 3000 specimens were tested across both programs, with an overall positivity rate of 2.5% and 3.6% in the personnel and cadaver screening programs, respectively. DISCUSSION: This screening program serves as an example of institutional investment in the safety of its faculty, staff, and students alike to address specific needs of a global pandemic.

The Roles of Hippo Signaling Transducers Yap and Taz in Chromatin Remodeling.

Hippo signaling controls cellular processes that ultimately impact organogenesis and homeostasis. Consequently, disease states including cancer can emerge when signaling is deregulated. The major pathway transducers Yap and Taz require cofactors to impart transcriptional control over target genes. Research into Yap/Taz-mediated epigenetic modifications has revealed their association with chromatin-remodeling complex proteins as a means of altering chromatin structure, therefore affecting accessibility and activity of target genes. Specifically, Yap/Taz have been found to associate with factors of the GAGA, Ncoa6, Mediator, Switch/sucrose nonfermentable (SWI/SNF), and Nucleosome Remodeling and Deacetylase (NuRD) chromatin-remodeling complexes to alter the accessibility of target genes. This review highlights the different mechanisms by which Yap/Taz collaborate with other factors to modify DNA packing at specific loci to either activate or repress target gene transcription.

Generation and characterization of mice harboring a conditional CXCL12 allele.

The chemokine CXCL12 has important functions in immune and central nervous systems. Moreover, a global disruption of CXCL12 in mice results in perinatal lethality. To circumvent this impediment and provide a tool for analyzing CXCL12 functions in specific organ systems, we have generated a mouse line harboring a loxP-site flanked exon 2 of CXCL12. A germ line deleter, ß-actin::cre was used to remove a CXCL12 exon 2 and subsequently systemic CXCL12 exon 2 deficient embryos were generated. These mutant embryos showed a marked depletion of CXCL12 transcript. As expected from the global mutant phenotype, our mutants were also characterized by highly irregular cerebellar cytoarchitecture of the external granule layer as well as altered radial migration of midbrain dopaminergic neurons. Importantly, migration of the pontine grey nucleus (PGN) was derailed and remarkably resembled the global mutant phenotype of the CXCL12 receptor - CXCR4 in this system. Despite the fact that CXCL12 signaling can be mediated through receptors other than CXCR4, our results indicate a monogamous relationship between the CXCL12 ligand and CXCR4 receptor in controlling PGN migration. Our findings further expand on the understanding of CXCL12 function in PGN development. Moreover, phenotypic similarities between our mutants and mice harboring a global CXCL12 disruption support the validity of our line. Importantly, these results strongly suggest that our conditional CXCL12 line can be used as a powerful tool to manipulate CXCL12 signaling and function in vivo.