How To Prepare for the Unexpected: a Public Health Laboratory Response.

Public health laboratories (PHLs) continue to face internal and external challenges to their abilities to provide successful, timely responses to public health crises and emerging threats. These laboratories are mandated to maintain the health of their communities by identifying, diagnosing, and warning constituents of potential and real health emergencies. Due to the changing characteristics of public health threats and their cross-jurisdictional nature, laboratories are facing increased pressure to ensure that they respond in a consistent and coordinated manner. Here, the Association of Public Health Laboratories (APHL) Emerging Leader Program Cohort 11 members have compiled stories from subject matter experts (SMEs) at PHLs with direct involvement in crises to determine the characteristics of a successful response. Experts examined a diverse selection of emerging threats from across PHLs, including infectious diseases, opioids, natural disasters, and government shutdowns. While no public health crisis will be identical to another, overarching themes were consistent across subjects. Experiences from SMEs that could improve future responses to emerging threats are highlighted.

A class I transgene reveals regulatory events on chromosome 1 marking peripheral T cell differentiation and memory.

T cells respond to external signals by altering patterns of gene expression. Our characterization of a transgenic mouse revealed a genetic locus that is specifically regulated in T cells. Elucidation of the factors controlling the expression of the marker transgene may reveal basic regulatory mechanisms used by T cells as they differentiate from naive to primed/memory T cells. Although endogenous MHC class I K(q) expression is normal in these animals, expression of the K(b) transgene differentiates naive from primed/memory T cells. K(bHigh) T cells bear the phenotypic and functional properties of primed/memory T cells, while K(bLow) T cells have naive phenotypes. The transition from K(bLow) to K(bHigh) appears to involve signals resulting from engagement of the TCR. We show that transgene integration has occurred on chromosome 1, between D1Mit365 and D1Mit191. The gene regulatory mechanisms directing expression of the locus marked by the transgene are distinct from those controlling other known T cell-related genes within this locus. Stimulation of K(bHigh) T cells results in the up-regulation of both the endogenous K(q) gene and the K(b) transgene. However, the same stimuli induce increased expression of only K(q) on K(bLow) T cells. This indicates that even though the transcription factors necessary for class I expression are present in K(bLow) T cells, the K(b) gene appears not to be accessible to these factors. These findings suggest a change in chromatin structure at the transgene integration site as cells progress from a naive to a primed/memory differentiation state.