The Canada Western Red Spring wheat (Triticum aestivum L.) cultivars AAC Concord, AAC Prevail, CDC Hughes, Lillian, Glenlea, and elite line BW961 express a spectrum of resistance to leaf rust caused by Puccinia triticina Eriks. This study aimed to identify and map the leaf rust resistance of the cultivars using three doubled haploid populations, AAC Prevail/BW961 (PB), CDC Hughes/AAC Concord (HC), and Lillian/Glenlea (LG). The populations were evaluated for seedling resistance in the greenhouse and adult plant disease response in the field at Morden, MB for 3 years and genotyped with the 90K wheat Infinium iSelect SNP array. Genetic maps were constructed to perform QTL analysis on the seedling and field leaf rust data. A total of three field leaf rust resistance QTL segregated in the PB population, five in the HC, and six in the LG population. In the PB population, BW961 contributed two QTL on chromosomes 2DS and 7DS, and AAC Prevail contributed a QTL on 4AL consistent across trials. Of the five QTL in HC, AAC Concord contributed two QTL on 4AL and 7AL consistent across trials and a QTL on 3DL.1 that provided seedling resistance only. CDC Hughes contributed two QTL on 1DS and 3DL.2. Lillian contributed four QTL significant in at least two of the three trials on 2BS, 4AL, 5AL, and 7AL, and Glenlea two QTL on 4BL and 7BL. The 1DS QTL from CDC Hughes, the 2DS from BW961, the 4AL from the AAC Prevail, AAC Concord, and Lillian, and the 7AL from AAC Concord and Lillian conferred seedling leaf rust resistance. The QTL on 4AL corresponded with Lr30 and was the same across cultivars AAC Prevail, AAC Concord, and Lillian, whereas the 7AL corresponding with LrCen was coincident between AAC Concord and Lillian. The 7DS and 2DS QTL in BW961 corresponded with Lr34 and Lr2a, respectively, and the 1DS QTL in CDC Hughes with Lr21. The QTL identified on 5AL could represent a novel gene. The results of this study will widen our knowledge of leaf rust resistance genes in Canadian wheat and their utilization in resistance breeding.
Abstract The activity of antibody-drug conjugates (ADCs) on cancer cells can be affected by a multitude of factors, such as binding affinity, rate of internalization, subcellular trafficking, and efficient drug release within the target cell population. Consequently, the properties of an ideal antibody for drug delivery are not necessarily the same as those for a therapeutic naked antibody. Furthermore, the use of indirect assays involving the use of secondary antibodies to screen for optimal ADCs can be misleading, since crosslinking on the cell surface can lead to altered downstream events, and the affinity of the secondary antibody constrains the dynamic range of the assay. When seeking candidate antibodies directed against a novel antigen for ADC therapy, it is therefore most desirable to screen a large panel in the form of ADCs and evaluate their cytotoxic activities, since these results provide a direct measurement of parameters that can affect cytotoxic activity. However, when dealing with microgram quantities of a large number of antibodies as is typical of an antibody discovery campaign, the yields from conventional conjugation methodologies are limiting. We developed a novel approach that addresses this issue and have successfully applied it to the discovery of optimal ADCs out of a large panel of candidate antibodies. The technology is currently being applied to the discovery of ADCs against antigens of interest for targeted drug delivery. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4394.
Fusarium head blight (FHB) is a highly destructive fungal disease of wheat to which host resistance is quantitatively inherited and largely influenced by the environment. Resistance to FHB has been associated with taller height and later maturity; however, a further understanding of these relationships is needed. An association mapping panel (AMP) of 192 predominantly Canadian spring wheat was genotyped with the wheat 90K single-nucleotide polymorphism (SNP) array. The AMP was assessed for FHB incidence (INC), severity (SEV) and index (IND), days to anthesis (DTA), and plant height (PLHT) between 2015 and 2017 at three Canadian FHB-inoculated nurseries. Seven multi-environment trial (MET) datasets were deployed in a genome-wide association study (GWAS) using a single-locus mixed linear model (MLM) and a multi-locus random SNP-effect mixed linear model (mrMLM). MLM detected four quantitative trait nucleotides (QTNs) for INC on chromosomes 2D and 3D and for SEV and IND on chromosome 3B. Further, mrMLM identified 291 QTNs: 50 (INC), 72 (SEV), 90 (IND), 41 (DTA), and 38 (PLHT). At two or more environments, 17 QTNs for FHB, DTA, and PLHT were detected. Of these 17, 12 QTNs were pleiotropic for FHB traits, DTA, and PLHT on chromosomes 1A, 1D, 2D, 3B, 5A, 6B, 7A, and 7B; two QTNs for DTA were detected on chromosomes 1B and 7A; and three PLHT QTNs were located on chromosomes 4B and 6B. The 1B DTA QTN and the three pleiotropic QTNs on chromosomes 1A, 3B, and 6B are potentially identical to corresponding quantitative trait loci (QTLs) in durum wheat. Further, the 3B pleiotropic QTN for FHB INC, SEV, and IND co-locates with TraesCS3B02G024900 within the Fhb1 region on chromosome 3B and is ~3 Mb from a cloned Fhb1 candidate gene TaHRC. While the PLHT QTN on chromosome 6B is putatively novel, the 1B DTA QTN co-locates with a disease resistance protein located ~10 Mb from a Flowering Locus T1-like gene TaFT3-B1, and the 7A DTA QTN is ~5 Mb away from a maturity QTL QMat.dms-7A.3 of another study. GWAS and QTN candidate genes enabled the characterization of FHB resistance in relation to DTA and PLHT. This approach should eventually generate additional and reliable trait-specific markers for breeding selection, in addition to providing useful information for FHB trait discovery.
Abstract Background Fusarium head blight (FHB) infection results in Fusarium damaged kernels (FDK) and deoxynivalenol (DON) contamination that are downgrading factors at the Canadian elevators. Durum wheat ( Triticum turgidum L. var. durum Desf.) is particularly susceptible to FHB and most of the adapted Canadian durum wheat cultivars are susceptible to moderately susceptible to this disease. However, the durum line DT696 is less susceptible to FHB than commercially grown cultivars. Little is known about genetic variation for durum wheat ability to resist FDK infection and DON accumulation. This study was undertaken to map genetic loci conferring resistance to DON and FDK resistance using a SNP high-density genetic map of a DT707/DT696 DH population and to identify SNP markers useful in marker-assisted breeding. One hundred twenty lines were grown in corn spawn inoculated nurseries near Morden, MB in 2015, 2016 and 2017 and the harvested seeds were evaluated for DON. The genetic map of the population was used in quantitative trait locus analysis performed with MapQTL.6® software. Results Four DON accumulation resistance QTL detected in two of the three years were identified on chromosomes 1 A, 5 A (2 loci) and 7 A and two FDK resistance QTL were identified on chromosomes 5 and 7 A in single environments. Although not declared significant due to marginal LOD values, the QTL for FDK on the 5 and 7 A were showing in other years suggesting their effects were real. DT696 contributed the favourable alleles for low DON and FDK on all the chromosomes. Although no resistance loci contributed by DT707, transgressive segregant lines were identified resulting in greater resistance than DT696. Breeder-friendly KASP markers were developed for two of the DON and FDK QTL detected on chromosomes 5 and 7 A. Markers flanking each QTL were physically mapped against the durum wheat reference sequence and candidate genes which might be involved in FDK and DON resistance were identified within the QTL intervals. Conclusions The DH lines harboring the desired resistance QTL will serve as useful resources in breeding for FDK and DON resistance in durum wheat. Furthermore, breeder-friendly KASP markers developed during this study will be useful for the selection of durum wheat varieties with low FDK and DON levels in durum wheat breeding programs.
This paper describes the technologies, collaborative processes, and artistic intents of the musical composition Engravings for Prepared Snare Drum, iPad, and Computer, which was composed by Timothy Polashek for percussionist Brad Meyer using a jointly created electroacoustic and interactive musical instrument. During performance, the percussionist equally manipulates and expresses through two surfaces, an iPad displaying an interactive touch screen and a snare drum augmented with various foreign objects, including a contact microphone adhered to the drumhead’s surface. A computer program created for this composition runs on a laptop computer in front of the percussionist. The software captures sound from the contact microphone and transforms this sound through audio signal processing controlled by the performer’s gestures on the iPad. The computer screen displays an animated graphic score, as well as the current states of iPad controls and audio signal processing, for the performer. Many compositional and technological approaches used in this project pay tribute to composer John Cage, since the premiere performance of Engravings for Prepared Snare Drum, iPad, and Computer took place in 2012, the centennial celebration of Cage’s birth year.
Abstract Breast cancer (BrCa) is one of the most common cancers diagnosed and is the second leading cause of cancer-related deaths of women in the United States. BrCa is divided into four major molecular subtypes; these categories are based upon the expression of hormone receptors (i.e., estrogen receptor (ER) and progesterone receptor (PR)), HER2/neu receptor, and proliferation rate. Of these subtypes triple negative (ER-, PR-, HER2-) BrCa are among the most lethal, are highly aggressive, have poor prognosis, limited treatment options, and lack effective targeted therapies. Our lab has shown p-21 activated kinase 1 (PAK1) protein expression increases with BrCa progression in human tumor samples. PAK1 is highly expressed in invasive tumor tissues in comparison to normal tissues. The role of PAK1 in BrCa development and progression is through its activity as a serine/threonine kinase involved in the regulation of several key oncogenic pathways (i.e., WNT/β-catenin and MAPK/ERK/JNK). Although PAK1 expression is increased in invasive tumor tissues, our studies have found that in human BrCa cell cultures PAK1 expression is independent of hormonal receptor status. Our hypothesis for this study is that triple negative BrCa cell lines are more reliant upon PAK1's activity for cell growth, survival, and motility. To test our hypothesis two triple negative BrCa cell lines, MDA-MB-231 and MDA-MB-468, and two ER+ BrCa cell lines, T47D and ZR75-1, were used. Our results demonstrate there are significantly higher levels of PAK1 protein in T47D and MDA-MB-468, compared to ZR75-1 and MDA-MB-231. To determine if the cells were reliant on the activity of PAK1 for cell viability, a trypan blue exclusion assay was performed. The PAK1 inhibitor 1,1′-Dithiodi-2-napthol (IPA-3) significantly inhibited all four BrCa cell lines, cell growth and viability in a dose-dependent manner. IPA-3 further inhibited cell proliferation of MDA-MB-468 (IC50 = 11.5μM), MDA-MB-231 (IC50 = 14.5μM), ZR75-1 (IC50 = 13.3μM), and T47D (IC50 = 17.1μM). IPA-3 also inhibited the phosphorylation and nuclear translocation of PAK1 in a dose-dependent manner in MDA-MB-231 cells. The inhibition of PAK1 by IPA-3 also significantly inhibited the migration of MDA-MB-231 cells in a time- and dose-dependent manner. The regulation of PAK1 activation by the WNT/β-catenin pathway was further explored in ER+ and triple negative BrCa cell lines. Additional studies are currently underway investigating the role of PAK1 activation on the MAPK/ERK/JNK pathway and its effects on cell migration and invasion. These studies explore the role of PAK-1 in triple negative BrCa cell growth, survival, motility, and oncogenic signaling. Further investigation of PAK1's targets within these signaling pathways will provide opportunities for the development of novel prevention and/or therapeutic strategies. Citation Format: Alexandra M. Fajardo, Tristan Browne, Hannah Graff, Kelly Kleier, Kyle Neltner, Courtney McCall, Brad Meyer, Larry Douglass, Julia Carter. Targeting PAK1 activity in breast cancer: Inhibition of cell growth, survival, motility, and signaling. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1024. doi:10.1158/1538-7445.AM2015-1024
