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Liu Z.,University of British Columbia | Hundal-Jabal N.,BC Cancer Research Agency | Wong M.,BC Cancer Research Agency | Yapp D.,BC Cancer Research Agency | And 3 more authors.
MedChemComm | Year: 2014

An 18F-heteroaryltrifluoroborate was designed as a novel radioprosthetic for PET imaging. The stability of the new prosthetic was confirmed using 19F-NMR spectroscopy: the solvolytic half-life was measured to be >16000 min. Conjugation to RGD gave a stable radiotracer precursor for kit-like labeling by 18F-19F isotope exchange in 15 min. The total radiosynthetic procedure including HPLC purification requires <45 min. A plasma stability assay showed negligible defluoridation following 150 min and stability is corroborated by in vivo imaging showing minimal bone uptake. With Curie levels of 18F- fluoride, yields of 20% and specific activities as high as 3 Ci μmol -1 (110 GBq μmol-1) are achieved (n = 3). © 2014 The Royal Society of Chemistry.

Liu Z.,University of British Columbia | Pourghiasian M.,Bc Cancer Research Agency | Radtke M.A.,University of British Columbia | Lau J.,Bc Cancer Research Agency | And 6 more authors.
Angewandte Chemie - International Edition | Year: 2014

A new zwitterionic organotrifluoroborate is appended to three radiosynthons that afford undergo facile bioconjugation to several clinically relevant peptides and one enzyme inhibitor. Molecularly complex bioconjugates are 18Flabeled in a single aqueous step in rapid time (< 15 min) without HPLC purification to afford tracers in good yields (> 200 mCi, 20-40%) at high specific activity (≥ 3 Ci/mmol) and at > 98% purity. PET imaging shows in vivo stability and tumor uptake. © 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fuller Z.L.,Pennsylvania State University | Haynes G.D.,Pennsylvania State University | Haynes G.D.,BC Cancer Research Agency | Richards S.,Baylor College of Medicine | Schaeffer S.W.,Pennsylvania State University
Genetics | Year: 2016

Chromosomal rearrangements can shape the structure of genetic variation in the genome directly through alteration of genes at breakpoints or indirectly by holding combinations of genetic variants together due to reduced recombination. The third chromosome of Drosophila pseudoobscura is a model system to test hypotheses about how rearrangements are established in populations because its third chromosome is polymorphic for >30 gene arrangements that were generated by a series of overlapping inversion mutations. Circumstantial evidence has suggested that these gene arrangements are selected. Despite the expected homogenizing effects of extensive gene flow, the frequencies of arrangements form gradients or clines in nature, which have been stable since the system was first described >80 years ago. Furthermore, multiple arrangements exist at appreciable frequencies across several ecological niches providing the opportunity for heterokaryotypes to form. In this study, we tested whether genes are differentially expressed among chromosome arrangements in first instar larvae, adult females and males. In addition, we asked whether transcriptional patterns in heterokaryotypes are dominant, semidominant, overdominant, or underdominant. We find evidence for a significant abundance of differentially expressed genes across the inverted regions of the third chromosome, including an enrichment of genes involved in sensory perception for males. We find the majority of loci show additivity in heterokaryotypes. Our results suggest that multiple genes have expression differences among arrangements that were either captured by the original inversion mutation or accumulated after it reached polymorphic frequencies, providing a potential source of genetic variation for selection to act upon. These data suggest that the inversions are favored because of their indirect effect of recombination suppression that has held different combinations of differentially expressed genes together in the various gene arrangement backgrounds. © 2016 by the Genetics Society of America.

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