Correction of congenital hyperbilirubinemia in homozygous Gunn rats by xenotransplantation of hamster livers

The homozygous Gunnj/jrat is an animal model for Crigler-Najjar syndrome in which the lack of the enzyme uridine diphosphoglucoronate-glucuronosyltransferase (UDP-GT) results in congenital unconjugated nonhemolytic hyperbilirubinemia. Because the binding of bilirubin to albumin in plasma varies from species to species, xenotransplantation (XTx) of liver afforded in this model the opportunity to study the interactions between xenoproteins of the donor and bilirubin of the recipient. For this purpose, orthotopic liver transplantation (OLTx) was performed from hamster to adult Gunnj/j rats. No immunosuppression (IS) was given to controls (Group I, n=5) and to OLTx recipients of syngeneic (Gunnj/j rat) grafts (Group II, n=5), whereas tacrolimus (1 mg/kg/day × 15 days, IM) and cyclophosphamide (8 mg/kg/day × 7 days, IP) were administered to animals receiving hamster xenografts (Group III, n=11). While untreated animals (Group I) died within 7 days (6.8±0.2 days) post-transplantation (Tx), the use however of IS resulted in prolonged (30.2±6.8 days) survival of xenogeneic recipients (Group III) who eventually succumbed to rejection. A precipitous decline in total serum bilirubin (TBili) from pre-operative levels of 5.3±1.0 mg/dL to 0.5±0.2 mg/dL was noted in both Group I and III animals, an observation that sustained itself only in the latter group during the course of their follow-up. The decrease in TBili was also associated with a contemporaneous increase in biliary concentration of conjugated bilirubin. No noticeable reversal of hyperbilirubinemia was however observed in OLTx recipients of syngeneic grafts (Group II). Taken together, these data suggest that hamster albumin and hepatocyte-associated xenoproteins and enzymes involved in the process of membrane transport and glucuronidation of bilirubin, functioned efficaciously after OLTx in Gunnj/jrats, resulting in the reversal of the inborn error of metabolism for the duration of follow-up. © Munksgaard, Copenhagen

In Vivo Quantification of Bone Strontium Using X-Ray Fluorescence

Strontium (Sr) is an element naturally present in the human skeleton and is acquired through dietary means. Exposure to strontium has been linked to both harmful and beneficial effects on skeletal health. Recently, the administration of strontium has been shown to induce a therapeutic effect of increasing bone strength and bone mineral density in women suffering from post-menopausal osteoporosis. The advent of this new therapy has warranted the continued development of an energy dispersive x-ray fluorescence (EDXRF) system that may be used as a diagnostic tool for non-invasive measuring and monitoring of in vivo bone strontium levels. This device is currently housed at McMaster University and has been previously optimized to measure bone strontium in vivo. One shortcoming with this system is the inability to quantify absolute amounts of bone strontium in vivo due to Sr x-ray absorption by soft-tissue overlying bone. This work describes an attempt to examine several imaging modalities to determine which modality may provide overlying tissue thickness readings with an acceptable range of accuracy to correct for Sr x-ray absorption. A performance comparison between magnetic resonance imaging, x-ray computed tomography, 8, 25 and 55 MHz ultrasound, in estimating the tissue thickness of seven cadaver fingers, illustrated that 55 MHz ultrasound provided a superior range of accuracy at 3.2%. It further indicated that the currently used 8 MHz ultrasound may be used to accurately estimate tissue thickness, though with a diminished accuracy of 6.6%. EDXRF measurements were performed on cadaver fingers ex vivo. Analysis of results indicated that quantification might be achieved if signals are normalizated to the 35 keV coherent scatter peak and correction of both soft-tissue absorption of Sr x-rays and differences in 125I excitation source activity are carried out. Four EDXRF measurements were performed on a strontium citrate supplemented individual starting six months after Sr medicating had begun. Analysis of strontium levels revealed that bone strontium was already at a plateau by the first measurement and that these levels did not change in the 6 months following.ThesisMaster of Science (MSc

Teaching Photosensitizers a New Trick: Red Light-Triggered G-Quadruplex Alkylation by Ligand Co-localization

peer reviewe

Adaptive sampling with PIXL on the Mars Perseverance rover

Planetary rovers can use onboard data analysis to adapt their measurement plan on the fly, improving the science value of data collected between commands from Earth. This paper describes the implementation of an adaptive sampling algorithm used by PIXL, the X-ray fluorescence spectrometer of the Mars 2020 Perseverance rover. PIXL is deployed using the rover arm to measure X-ray spectra of rocks with a scan density of several thousand points over an area of typically 5 x 7 mm. The adaptive sampling algorithm is programmed to recognize points of interest and to increase the signal-to-noise ratio at those locations by performing longer integrations. Two approaches are used to formulate the sampling rules based on past quantification data: 1) Expressions that isolate particular regions within a ternary compositional diagram, and 2) Machine learning rules that threshold for a high weight percent of particular compounds. The design of the rulesets are outlined and the performance of the algorithm is quantified using measurements from the surface of Mars. To our knowledge, PIXL's adaptive sampling represents the first autonomous decision-making based on real-time compositional analysis by a spacecraft on the surface of another planet.Comment: 24 pages including 11 figures and 7 tables. Submitted for publication to the journal Icaru