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Background/Objectives: Clinically inactive corneal scars have repeatedly been shown to exhibit histological inflammation. This study aimed to evaluate the degree of histological inflammation in clinically inactive corneal scars of different origins and its correlation with graft rejection and failure following penetrating keratoplasty. Methods: The study included 205 primary corneal explants with clinically inactive central scars resulting from herpes simplex virus keratitis (HSV, n = 55), keratoconus (n = 39), mechanical trauma (n = 27), scrophulosa (n = 22) or other/unknown causes (n = 62). Central histological sections were categorized by the degree of inflammation, and an overall inflammation score (IS) was calculated. Results: HSV-associated scars exhibited a trend towards more graft rejection with higher IS (p = 0.074). Keratoconus-associated scars showed no IS-dependent differences in graft rejection or failure. The rejection rate in this group was 13/39. Scars resulting from mechanical trauma, such as perforating injuries, demonstrated a trend towards higher graft rejection (p = 0.15) and failure rates (p = 0.089) with increasing IS. The rejection rate in this group was 11/27. Scrophulosa-associated scars had significantly higher graft rejection rates (p = 0.041) at a lower cut-off of 0.06 compared to the cut-off of 0.36 for the other groups. Scars of other or unknown causes showed no IS-dependent differences in graft rejection or failure. Conclusions: Histological inflammation in HSV scars and scars resulting from mechanical trauma appeared to contribute to graft rejection. Despite low IS, the rejection rate in keratoconus scars and scars following mechanical trauma was unexpectedly high, indicating the presence of other influencing factors. While some correlations did not reach statistical significance due to small sample sizes in the subgroups, the observed trends should be considered clinically relevant. The study may have been "underpowered", as histopathologically inflamed specimens with clinically inactive corneal scars are relatively rare. [ABSTRACT FROM AUTHOR]

The DNA damage response in mycobacteria is controlled by the heterodimeric transcription factor PafBC, a member of the WYL domain-containing protein family. It has been shown that PafBC induces transcription of its regulon by reprogramming the housekeeping RNA polymerase holoenzyme to recognize PafBC-dependent promoters through sigma adaptation. However, the mechanism by which DNA damage is sensed and translated into PafBC activation has remained unclear. Here, we demonstrate that the binding of single-stranded DNA (ssDNA) to the WYL domains of PafBC activates the transcription factor. Our cryo-electron microscopy structure of full-length PafBC in its active conformation, bound to the transcription initiation complex, reveals a previously unknown mode of interaction between the ssDNA and the WYL domains. Using biochemical experiments, we show that short ssDNA fragments bind to PafBC dynamically, resulting in deactivation as ssDNA levels decrease postrepair. Our findings shed light on the mechanism linking DNA damage to PafBC activation and expand our understanding of WYL domain-containing proteins. [ABSTRACT FROM AUTHOR]