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  • Research data . 2017
    Open Access
    Authors: 
    Mazo, Alexander;
    Project: CIHR

    Original images associated with MOLECULAR-CELL-D-16-01448R2.

  • Open Access
    Authors: 
    Mehdi, Ali; Cheishvili, David; Arakelian, Ani; Bismar, Tarek A.; Szyf, Moshe; Rabbani, Shafaat A.;
    Publisher: figshare
    Project: CIHR

    Additional file 3: Supplementary Table 2. List of the primers used for pyrosequencing and amplicon sequencing (Illumina MiSeq system).

  • Open Access
    Authors: 
    Guanxiang Liang; Nilusha Malmuthuge; Bao, Hua; Stothard, Paul; Griebel, Philip; Guan, Le;
    Publisher: Figshare
    Project: CIHR , NSERC

    Regionally DE genes list. (XLSX 282Â kb)

  • Open Access
    Authors: 
    Liu, Chengyou; Hogan, Andrew M.; Sturm, Hunter; Khan, Mohd Wasif; Islam, Md. Mohaiminul; Rahman, A. S. M. Zisanur; Davis, Rebecca; Cardona, Silvia T.; Hu, Pingzhao;
    Publisher: figshare
    Project: CIHR

    Additional file 3: Table S2. Annotation of the M. Tuberculosis genes and clusters. M. tuberculosis genes are represented by gene symbols and the protein RefSeq ID and COG category eggNOG.

  • Open Access
    Authors: 
    Hyshka, Elaine; Jalene Anderson-Baron; Kamagaju Karekezi; Belle-Isle, Lynne; Elliott, Richard; Pauly, Bernie; Strike, Carol; Asbridge, Mark; Dell, Colleen; McBride, Keely; +2 more
    Publisher: Figshare
    Project: CIHR

    Provincial and territorial policy documents and indicator scores; table contains all CHARPP indicator scores from 13 provincial and territorial harm reduction policy report cards. (XLSX 57Â kb)

  • Open Access
    Authors: 
    Liu, Feng; Cai, Ping; Imir Metushi; Jinze Li; Nakayawa, Tetsuya; Libia Vega; Uetrecht, Jack;
    Publisher: Taylor & Francis
    Project: CIHR

    Amodiaquine (AQ) is associated with a relatively high incidence of idiosyncratic drug-induced liver injury (IDILI) and agranulocytosis. A previous study reported that a combination of high dose AQ and glutathione (GSH) depletion led to liver injury. However, the characteristics of this toxicity were very different from AQ-induced liver injury in humans. We developed a model of AQ-induced liver injury with characteristics similar to the injury in humans by treating mice with lower doses of AQ for several weeks. In this study we found that not only did GSH depletion not increase AQ covalent binding to hepatic proteins at this lower dose, but also it paradoxically prevented the liver injury. We extended the model to rats and found AQ treatment led to a mild delayed onset liver injury that resolved despite continued treatment with AQ. Immunohistochemistry indicated the presence of Kupffer cell activation, apoptosis and hepatocyte proliferation in the liver. There was also an increase in serum IL-2, IL-5, IL-9, IL-12, MCP-1 and TGFβ, but a decrease in leptin. Coincident with the elevated serum ALT, the number of liver CD4+ T-cells, IL-17 secreting cells and TH17/Treg cells increased at Week 3 and decreased during continued treatment. Increases in NK1.1+ cells and activated M2 macrophages were also observed during liver injury. These results suggest that the outcome of the liver injury was determined by the balance between effector and regulatory cells. Co-treatment with cyclosporin prevented AQ-induced liver injury, which supports an immune mechanism. Retinoic acid (RA), which has been reported to enhance natural killer (NK) cell activity, exacerbated AQ-induced liver injury. These results suggest that AQ-induced IDILI is immune mediated and the subsequent adaptation appears to represent immune tolerance.

  • Open Access
    Authors: 
    Wadsworth, Brennan J.; Decotret, Lisa R.; Villamil, Carlos; Yapp, Donald; Wilson, Don; Benard, Francois; McKenzie, Michael; Bennewith, Kevin L.;
    Publisher: Taylor & Francis
    Project: CIHR

    A common feature of solid tumours that are resistant to therapy is the presence of regions with low oxygen content (i.e., hypoxia). Oxygen electrode studies suggest that localized prostate adenocarcinoma is commonly hypoxic, although conflicting data have been reported between immunohistochemical detection of hypoxia-induced proteins in biopsy specimens and positron emission tomography (PET) imaging of 18F-labeled hypoxia reporters. Although the 2-nitroimidazole 18F-EF5 is well-established to label hypoxic tumour cells in pre-clinical tumour models and clinical trials of multiple primary tumour sites, it has yet to be tested in prostate cancer. The purpose of this study was to evaluate the feasibility of using 18F-EF5 to detect hypoxia in clinical prostate tumours. Patients with localized adenocarcinoma of the prostate were recruited for pre-treatment 18F-EF5 PET scans. Immunohistochemistry was conducted on diagnostic biopsies to assess the expression of glucose transporter 1 (GLUT1), osteopontin (OPN), and carbonic anhydrase IX (CAIX). Immunoreactivity scores of staining intensity and frequency were used to indicate the presence of tumour hypoxia. We found low tumour-to-muscle ratios of 18F-EF5 uptake that were not consistent with tumour hypoxia, causing early termination of the study. However, we observed GLUT1 and OPN expression in all prostate tumour biopsies, indicating the presence of hypoxia in all tumours. Our data do not support the use of 18F-EF5 PET to detect hypoxia in prostate adenocarcinoma, and suggest the use of immunohistochemistry to quantify expression of the hypoxia-inducible proteins GLUT1 and OPN as indications of prostate tumour hypoxia.

  • Open Access
    Authors: 
    Chen, Ying; Monaco, Simona; Crawford, Douglas J;
    Publisher: Wiley
    Project: CIHR

    Targets for goal-directed action can be encoded in allocentric coordinates (relative to another visual landmark), but it is not known how these are converted into egocentric commands for action. Here, we investigated this using a slow event-related fMRI paradigm, based on our previous behavioral finding that the Allocentric to Egocentric (Allo-Ego) conversion for reach is done at the first possible opportunity. Participants were asked to remember (and eventually reach toward) the location of a briefly presented target relative to another visual landmark. After a 1st memory delay, participants were forewarned by a verbal instruction if the landmark would reappear at the same location, (potentially allowing them to plan a reach following the auditory cue before the 2nd delay), or at a different location where they had to wait for the final landmark to be presented before response, and then reach toward the remembered target location. As predicted, participants showed landmark-centered directional selectivity in occipital-temporal cortex during the first memory delay, only developed egocentric directional selectivity in occipital-parietal cortex during the second delay for the “Same cue” task, and during response for the “Different cue” task. We then compared cortical activation between these two tasks at the times when the Allo-Ego conversion occurred, and found common activation in right precuneus, right pre-supplementary area and bilateral dorsal premotor cortex. These results confirm that the brain converts allocentric codes to egocentric plans at the first possible opportunity, and identify the four most likely candidate sites specific to the Allo-Ego transformation for reaches.

  • Open Access
    Authors: 
    Fudge, Neva J.; Mearow, Karen M.;
    Publisher: Dryad
    Project: CIHR , NSERC

    Background: In our previous investigations of the role of the extracellular matrix (ECM) in promoting neurite growth we have observed that a permissive laminin (LN) substrate stimulates differential growth responses in subpopulations of mature dorsal root ganglion (DRG) neurons. DRG neurons expressing Trk and p75 receptors grow neurites on a LN substrate in the absence of neurotrophins, while isolectin B4-binding neurons (IB4+) do not display significant growth under the same conditions. We set out to determine whether there was an expression signature of the LN-induced neurite growth phenotype. Using a lectin binding protocol IB4+ neurons were isolated from dissociated DRG neurons, creating two groups - IB4+ and IB4-. A small-scale microarray approach was employed to screen the expression of a panel of ECM-associated genes following dissociation (t=0) and after 24 hr culture on LN (t=24LN). This was followed by qRT-PCR and immunocytochemistry of selected genes. Results: The microarray screen showed that 36 of the 144 genes on the arrays were consistently expressed by the neurons. The array analyses showed that six genes had lower expression in the IB4+ neurons compared to the IB4- cells at t=0 (CTSH, Icam1, Itgβ1, Lamb1, Plat, Spp1), and one gene was expressed at higher levels in the IB4+ cells (Plaur). qRT-PCR was carried out as an independent assessment of the array results. There were discrepancies between the two methods, with qRT-PCR confirming the differences in Lamb1, Plat and Plaur, and showing decreased expression of AdamTs1, FN, and Icam in the IB4+ cells at t=0. After 24 hr culture on LN, there were no significant differences detected by qRT-PCR between the IB4+ and IB4- cells. However, both groups showed upregulation of Itgβ1 and Plaur after 24 hr on LN, the IB4+ group also had increased Plat, and the IB4- cells showed decreased Lamb1, Icam1 and AdamTs1. Further, the array screen also detected a number of genes (not subjected to qRT-PCR) expressed similarly by both populations in relatively high levels but not detectably influenced by time in culture (Bsg, Cst3, Ctsb, Ctsd, Ctsl, Mmp14, Mmp19, Sparc. We carried out immunohistochemistry to confirm expression of proteins encoded by a number of these genes. Conclusions:Our results show that 1B4+ and IB4- neurons differ in the expression of several genes that are associated with responsiveness to the ECM prior to culturing (AdamTs1, FN, Icam1, Lamb1, Plat, Plaur). The data suggest that the genes expressed at higher levels in the IB4- neurons could contribute to the initial growth response of these cells in a permissive environment and could also represent a common injury response that subsequently promotes axon regeneration. The differential expression of several extracellular matrix molecules (FN, Lamb1, Icam) may suggest that the IB4- neurons are capable of maintaining /secreting their local extracellular environment which could aid in the regenerative process. Overall, these data provide new information on potential targets that could be manipulated to enhance axonal regeneration in the mature nervous system.

  • Open Access
    Authors: 
    Chignon, Arnaud; Mathieu, Samuel; Rufiange, Anne; Argaud, D��borah; Voisine, Pierre; Boss��, Yohan; Arsenault, Benoit J.; Th��riault, S��bastien; Mathieu, Patrick;
    Publisher: figshare
    Project: CIHR

    Additional file 2. Supplemental Table 2: DEPICT genetic association in pathways.

search
Include:
The following results are related to Canada. Are you interested to view more results? Visit OpenAIRE - Explore.
1,300 Research products, page 1 of 130
  • Research data . 2017
    Open Access
    Authors: 
    Mazo, Alexander;
    Project: CIHR

    Original images associated with MOLECULAR-CELL-D-16-01448R2.

  • Open Access
    Authors: 
    Mehdi, Ali; Cheishvili, David; Arakelian, Ani; Bismar, Tarek A.; Szyf, Moshe; Rabbani, Shafaat A.;
    Publisher: figshare
    Project: CIHR

    Additional file 3: Supplementary Table 2. List of the primers used for pyrosequencing and amplicon sequencing (Illumina MiSeq system).

  • Open Access
    Authors: 
    Guanxiang Liang; Nilusha Malmuthuge; Bao, Hua; Stothard, Paul; Griebel, Philip; Guan, Le;
    Publisher: Figshare
    Project: CIHR , NSERC

    Regionally DE genes list. (XLSX 282Â kb)

  • Open Access
    Authors: 
    Liu, Chengyou; Hogan, Andrew M.; Sturm, Hunter; Khan, Mohd Wasif; Islam, Md. Mohaiminul; Rahman, A. S. M. Zisanur; Davis, Rebecca; Cardona, Silvia T.; Hu, Pingzhao;
    Publisher: figshare
    Project: CIHR

    Additional file 3: Table S2. Annotation of the M. Tuberculosis genes and clusters. M. tuberculosis genes are represented by gene symbols and the protein RefSeq ID and COG category eggNOG.

  • Open Access
    Authors: 
    Hyshka, Elaine; Jalene Anderson-Baron; Kamagaju Karekezi; Belle-Isle, Lynne; Elliott, Richard; Pauly, Bernie; Strike, Carol; Asbridge, Mark; Dell, Colleen; McBride, Keely; +2 more
    Publisher: Figshare
    Project: CIHR

    Provincial and territorial policy documents and indicator scores; table contains all CHARPP indicator scores from 13 provincial and territorial harm reduction policy report cards. (XLSX 57Â kb)

  • Open Access
    Authors: 
    Liu, Feng; Cai, Ping; Imir Metushi; Jinze Li; Nakayawa, Tetsuya; Libia Vega; Uetrecht, Jack;
    Publisher: Taylor & Francis
    Project: CIHR

    Amodiaquine (AQ) is associated with a relatively high incidence of idiosyncratic drug-induced liver injury (IDILI) and agranulocytosis. A previous study reported that a combination of high dose AQ and glutathione (GSH) depletion led to liver injury. However, the characteristics of this toxicity were very different from AQ-induced liver injury in humans. We developed a model of AQ-induced liver injury with characteristics similar to the injury in humans by treating mice with lower doses of AQ for several weeks. In this study we found that not only did GSH depletion not increase AQ covalent binding to hepatic proteins at this lower dose, but also it paradoxically prevented the liver injury. We extended the model to rats and found AQ treatment led to a mild delayed onset liver injury that resolved despite continued treatment with AQ. Immunohistochemistry indicated the presence of Kupffer cell activation, apoptosis and hepatocyte proliferation in the liver. There was also an increase in serum IL-2, IL-5, IL-9, IL-12, MCP-1 and TGFβ, but a decrease in leptin. Coincident with the elevated serum ALT, the number of liver CD4+ T-cells, IL-17 secreting cells and TH17/Treg cells increased at Week 3 and decreased during continued treatment. Increases in NK1.1+ cells and activated M2 macrophages were also observed during liver injury. These results suggest that the outcome of the liver injury was determined by the balance between effector and regulatory cells. Co-treatment with cyclosporin prevented AQ-induced liver injury, which supports an immune mechanism. Retinoic acid (RA), which has been reported to enhance natural killer (NK) cell activity, exacerbated AQ-induced liver injury. These results suggest that AQ-induced IDILI is immune mediated and the subsequent adaptation appears to represent immune tolerance.

  • Open Access
    Authors: 
    Wadsworth, Brennan J.; Decotret, Lisa R.; Villamil, Carlos; Yapp, Donald; Wilson, Don; Benard, Francois; McKenzie, Michael; Bennewith, Kevin L.;
    Publisher: Taylor & Francis
    Project: CIHR

    A common feature of solid tumours that are resistant to therapy is the presence of regions with low oxygen content (i.e., hypoxia). Oxygen electrode studies suggest that localized prostate adenocarcinoma is commonly hypoxic, although conflicting data have been reported between immunohistochemical detection of hypoxia-induced proteins in biopsy specimens and positron emission tomography (PET) imaging of 18F-labeled hypoxia reporters. Although the 2-nitroimidazole 18F-EF5 is well-established to label hypoxic tumour cells in pre-clinical tumour models and clinical trials of multiple primary tumour sites, it has yet to be tested in prostate cancer. The purpose of this study was to evaluate the feasibility of using 18F-EF5 to detect hypoxia in clinical prostate tumours. Patients with localized adenocarcinoma of the prostate were recruited for pre-treatment 18F-EF5 PET scans. Immunohistochemistry was conducted on diagnostic biopsies to assess the expression of glucose transporter 1 (GLUT1), osteopontin (OPN), and carbonic anhydrase IX (CAIX). Immunoreactivity scores of staining intensity and frequency were used to indicate the presence of tumour hypoxia. We found low tumour-to-muscle ratios of 18F-EF5 uptake that were not consistent with tumour hypoxia, causing early termination of the study. However, we observed GLUT1 and OPN expression in all prostate tumour biopsies, indicating the presence of hypoxia in all tumours. Our data do not support the use of 18F-EF5 PET to detect hypoxia in prostate adenocarcinoma, and suggest the use of immunohistochemistry to quantify expression of the hypoxia-inducible proteins GLUT1 and OPN as indications of prostate tumour hypoxia.

  • Open Access
    Authors: 
    Chen, Ying; Monaco, Simona; Crawford, Douglas J;
    Publisher: Wiley
    Project: CIHR

    Targets for goal-directed action can be encoded in allocentric coordinates (relative to another visual landmark), but it is not known how these are converted into egocentric commands for action. Here, we investigated this using a slow event-related fMRI paradigm, based on our previous behavioral finding that the Allocentric to Egocentric (Allo-Ego) conversion for reach is done at the first possible opportunity. Participants were asked to remember (and eventually reach toward) the location of a briefly presented target relative to another visual landmark. After a 1st memory delay, participants were forewarned by a verbal instruction if the landmark would reappear at the same location, (potentially allowing them to plan a reach following the auditory cue before the 2nd delay), or at a different location where they had to wait for the final landmark to be presented before response, and then reach toward the remembered target location. As predicted, participants showed landmark-centered directional selectivity in occipital-temporal cortex during the first memory delay, only developed egocentric directional selectivity in occipital-parietal cortex during the second delay for the “Same cue” task, and during response for the “Different cue” task. We then compared cortical activation between these two tasks at the times when the Allo-Ego conversion occurred, and found common activation in right precuneus, right pre-supplementary area and bilateral dorsal premotor cortex. These results confirm that the brain converts allocentric codes to egocentric plans at the first possible opportunity, and identify the four most likely candidate sites specific to the Allo-Ego transformation for reaches.

  • Open Access
    Authors: 
    Fudge, Neva J.; Mearow, Karen M.;
    Publisher: Dryad
    Project: CIHR , NSERC

    Background: In our previous investigations of the role of the extracellular matrix (ECM) in promoting neurite growth we have observed that a permissive laminin (LN) substrate stimulates differential growth responses in subpopulations of mature dorsal root ganglion (DRG) neurons. DRG neurons expressing Trk and p75 receptors grow neurites on a LN substrate in the absence of neurotrophins, while isolectin B4-binding neurons (IB4+) do not display significant growth under the same conditions. We set out to determine whether there was an expression signature of the LN-induced neurite growth phenotype. Using a lectin binding protocol IB4+ neurons were isolated from dissociated DRG neurons, creating two groups - IB4+ and IB4-. A small-scale microarray approach was employed to screen the expression of a panel of ECM-associated genes following dissociation (t=0) and after 24 hr culture on LN (t=24LN). This was followed by qRT-PCR and immunocytochemistry of selected genes. Results: The microarray screen showed that 36 of the 144 genes on the arrays were consistently expressed by the neurons. The array analyses showed that six genes had lower expression in the IB4+ neurons compared to the IB4- cells at t=0 (CTSH, Icam1, Itgβ1, Lamb1, Plat, Spp1), and one gene was expressed at higher levels in the IB4+ cells (Plaur). qRT-PCR was carried out as an independent assessment of the array results. There were discrepancies between the two methods, with qRT-PCR confirming the differences in Lamb1, Plat and Plaur, and showing decreased expression of AdamTs1, FN, and Icam in the IB4+ cells at t=0. After 24 hr culture on LN, there were no significant differences detected by qRT-PCR between the IB4+ and IB4- cells. However, both groups showed upregulation of Itgβ1 and Plaur after 24 hr on LN, the IB4+ group also had increased Plat, and the IB4- cells showed decreased Lamb1, Icam1 and AdamTs1. Further, the array screen also detected a number of genes (not subjected to qRT-PCR) expressed similarly by both populations in relatively high levels but not detectably influenced by time in culture (Bsg, Cst3, Ctsb, Ctsd, Ctsl, Mmp14, Mmp19, Sparc. We carried out immunohistochemistry to confirm expression of proteins encoded by a number of these genes. Conclusions:Our results show that 1B4+ and IB4- neurons differ in the expression of several genes that are associated with responsiveness to the ECM prior to culturing (AdamTs1, FN, Icam1, Lamb1, Plat, Plaur). The data suggest that the genes expressed at higher levels in the IB4- neurons could contribute to the initial growth response of these cells in a permissive environment and could also represent a common injury response that subsequently promotes axon regeneration. The differential expression of several extracellular matrix molecules (FN, Lamb1, Icam) may suggest that the IB4- neurons are capable of maintaining /secreting their local extracellular environment which could aid in the regenerative process. Overall, these data provide new information on potential targets that could be manipulated to enhance axonal regeneration in the mature nervous system.

  • Open Access
    Authors: 
    Chignon, Arnaud; Mathieu, Samuel; Rufiange, Anne; Argaud, D��borah; Voisine, Pierre; Boss��, Yohan; Arsenault, Benoit J.; Th��riault, S��bastien; Mathieu, Patrick;
    Publisher: figshare
    Project: CIHR

    Additional file 2. Supplemental Table 2: DEPICT genetic association in pathways.