Donor-directed immunologic safety of COVID-19 vaccination in renal transplant recipients.

Infection risk and COVID-19 outcomes make SARS-CoV-2 vaccination essential forsolid-organ transplant recipients. Reports of immune activation after vaccination causing graft failure raise concerns, but data are limited. Here, we document graft function, donor-derived-cell-free-DNA(dd-cfDNA), and donor-specific antibodies (DSA) in solid-organ renal transplant recipients after vaccination. Retrospective demographics, graft function, and immunologic parameters were collected in 96 renal transplant patients one month after their second vaccine dose. For-cause biopsies were performed based on clinician judgment. Similar proportions of subjects experienced increases (39.6 %) and decreases (44.8 %) in serum creatinine in the post-vaccination period, p = 0.56. Similar proportions of subjects experienced increases (23 %) and decreases (25 %) in serum ddcfDNA in the post-vaccination period, p = 0.87. Post-vaccination changes in serum creatinine and ddcfDNA (r(95) = -0.04, p = 0.71), serum creatinine and cumulative DSA MFI (r(95) = 0.07, p = 0.56), and ddcfDNA and cumulative DSA MFI(r(95) = 0.13, p = 0.21) were not significantly correlated. Five subjects had increased cumulativeDSA MFI, but there were no de novo cases. Biopsies on three subjects confirmed pre-existing diagnoses. Our study found minimal evidence ofdonor-directed immunologic activity post-vaccination, and all immunologic changesdid not correlate to graft dysfunction. We believe these findings do not amount to evidence ofpost-vaccination deleterious donor-directed activation. SARS-CoV-2 vaccination is immunologically safe and should continue for renal transplant recipients.

Adverse effects from environmental mercury loads on breeding common loons.

Anthropogenic inputs of mercury (Hg) into the environment have significantly increased in the past century. Concurrently, the availability of methylmercury (MeHg) in aquatic systems has increased to levels posing risks to ecological and human health. We use the common loon (Gavia immer) as an upper trophic level bioindicator of aquatic Hg toxicity in freshwater lakes. Multiple endpoints were selected to measure potential negative impacts from MeHg body burdens on behavior, physiology, survival and reproductive success. A robust spatio-temporal dataset was used that included nearly 5,500 loon Hg measurements over an 18-year period. We measured significant changes related to elevated MeHg body burdens, including aberrant incubation behavior, lethargy, and wing area asymmetry. Mercury body burdens in adult loons increased an average of 8.4% per year. Increasing Hg body burdens reduced the number of fledged chicks per territorial pair, with highest risk loons producing 41% fewer fledged young than our reference group. Our multiple endpoints establish adverse effect thresholds for adult loons at 3.0 ug/g (wet weight) in blood and 40.0 ug/g (fresh weight) in feathers. Mercury contamination in parts of Maine and New Hampshire is a driving stressor for creating breeding population sinks. Standardized monitoring programs are needed to determine if population sinks occur elsewhere and to track aquatic ecosystem responses to changes in Hg emissions and deposition.

Hedgehog signaling maintains resident hepatic progenitors throughout life.

Hedgehog signaling through its receptor, Patched, activates transcription of genes, including Patched, that regulate the fate of various progenitors. Although Hedgehog signaling is required for endodermal commitment and hepatogenesis, the possibility that it regulates liver turnover in adults had not been considered because mature liver epithelial cells lack Hedgehog signaling. Herein, we show that this pathway is essential throughout life for maintaining hepatic progenitors. Patched-expressing cells have been identified among endodermally lineage-restricted, murine embryonic stem cells as well as in livers of fetal and adult Ptc-lacZ mice. An adult-derived, murine hepatic progenitor cell line expresses Patched, and Hedgehog-responsive cells exist in stem cell compartments of fetal and adult human livers. In both species, manipulation of Hedgehog activity influences hepatic progenitor cell survival. Therefore, Hedgehog signaling is conserved in hepatic progenitors from fetal development through adulthood and may be a new therapeutic target in patients with liver damage.

Proliferation and hepatic differentiation of adult-derived progenitor cells.

Hepatic progenitor cells, capable of maturing into hepatocytes and biliary cells, are hypothesized to be involved in all forms of liver regeneration and may prove clinically useful at reconstituting damaged livers. A murine hepatic progenitor cell population from young adult liver tissue has been isolated and characterized to establish a model for the development of liver cell therapies and for analysis of immune responses after transplantation. Hepatic progenitor cells were isolated from 3- to 6-week-old C57BL/6 mice using modifications of a two-stage liver perfusion technique followed by low speed centrifugation. Cellular analysis by phase contrast, fluorescent and confocal microscopy demonstrated that the hepatic progenitors (1) formed ex vivo colonies with a morphological appearance similar to committed hepatocytic progenitors isolated from embryonic mice and rats; (2) they are smaller than mature hepatocytes; (3) in culture they demonstrated peak expression of an oval cell marker at day 14, whereas albumin expression continued to increase beyond day 21 of culture, and (4) a subset of the progenitors phenotypically differentiated into mature hepatocytes or biliary cells. The unique antigenic profile of these hepatic progenitor cells and their ability to differentiate suggests that purification of the cells should allow for their potential use in transplantation.