Immune Regulation in Time and Space: The Role of Local- and Long-Range Genomic Interactions in Regulating Immune Responses.

Mammals face and overcome an onslaught of endogenous and exogenous challenges in order to survive. Typical immune cells and barrier cells, such as epithelia, must respond rapidly and effectively to encountered pathogens and aberrant cells to prevent invasion and eliminate pathogenic species before they become overgrown and cause harm. On the other hand, inappropriate initiation and failed termination of immune cell effector function in the absence of pathogens or aberrant tissue gives rise to a number of chronic, auto-immune, and neoplastic diseases. Therefore, the fine control of immune effector functions to provide for a rapid, robust response to challenge is essential. Importantly, immune cells are heterogeneous due to various factors relating to cytokine exposure and cell-cell interaction. For instance, tissue-resident macrophages and T cells are phenotypically, transcriptionally, and functionally distinct from their circulating counterparts. Indeed, even the same cell types in the same environment show distinct transcription patterns at the single cell level due to cellular noise, despite being robust in concert. Additionally, immune cells must remain quiescent in a naive state to avoid autoimmunity or chronic inflammatory states but must respond robustly upon activation regardless of their microenvironment or cellular noise. In recent years, accruing evidence from next-generation sequencing, chromatin capture techniques, and high-resolution imaging has shown that local- and long-range genome architecture plays an important role in coordinating rapid and robust transcriptional responses. Here, we discuss the local- and long-range genome architecture of immune cells and the resultant changes upon pathogen or antigen exposure. Furthermore, we argue that genome structures contribute functionally to rapid and robust responses under noisy and distinct cellular environments and propose a model to explain this phenomenon.

The role of the University of Cape Town, South Africa in the training and retention of surgeons in Sub-Saharan Africa.

BACKGROUND: Sub-Saharan Africa (SSA) has a shortage of surgeon specialists. Many SSA countries lack specialty training programs but South Africa, an upper middle-income country, has several post-graduate surgical training programs. The primary objective of this study was to describe the retention rates of non-South African SSA surgical trainees from the University of Cape Town (UCT) on the African sub-continent. The secondary objective was to describe advantages and disadvantages of foreign surgical trainees on the UCT surgical training programs. METHODS: This was a two-part cross-sectional survey administered via email between June 1, 2018 and March 1, 2019 to UCT 1) surgical residents and fellows who graduated between 2007 and 2017 and whose country of origin was in SSA but outside South Africa, and 2) UCT surgical division heads. RESULTS: Thirty out of 78 (38%) trainees responded; 83% (n = 25) were male. There was a 96% retention rate of surgical trainees in SSA, 80% (n = 24) returned to their country of origin after training, 83% (n = 25) worked in the public sector, and 90% (n = 27) in teaching hospitals. Seven out of ten surgical division heads responded. Reported advantages of SSA trainees included more junior staff (n = 5, 71%) and the establishment of SSA networks (n = 4, 57%). Disadvantages included increased training responsibilities for educators (n = 2, 29%) and fewer cases for South African trainees (n = 2, 29%). DISCUSSION: Retention on the African sub-continent of surgeons who trained at UCT was high. SSA doctors can utilize South African post-graduate surgical training programs until their own countries increase their training capacity. The majority of trainees returned to their countries of origin, utilizing their skills in the public and academic sectors, and contributing to the teaching of more trainees. These training partnerships also contribute to knowledge-sharing and facilitate a regional network of African surgeons. Active recruitment of more female trainees is needed to ensure gender equity.