ORCID Profile
0000-0002-7026-3880
Current Organisations
Université de Sherbrooke
,
University of Queensland
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Publisher: Wiley
Date: 31-12-2019
DOI: 10.1111/GCB.14904
Abstract: Plant traits—the morphological, anatomical, physiological, biochemical and phenological characteristics of plants—determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to bio ersity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits—almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on in idual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
Publisher: Wiley
Date: 18-09-2021
DOI: 10.1111/IMCB.12499
Abstract: Group A Streptococcus (GAS) is a Gram‐positive bacterial pathogen that causes an array of infectious diseases in humans. Accumulating clinical evidence suggests that proinflammatory interleukin (IL)‐1β signaling plays an important role in GAS disease progression. The host regulates the production and secretion of IL‐1β via the cytosolic inflammasome pathway. Activation of the NLR family pyrin domain‐containing 3 (NLRP3) inflammasome complex requires two signals: a priming signal that stimulates increased transcription of genes encoding the components of the inflammasome pathway, and an activating signal that induces assembly of the inflammasome complex. Here we show that GAS‐derived lipoteichoic acid can provide a priming signal for NLRP3 inflammasome activation. As only few GAS‐derived proteins have been associated with inflammasome‐dependent IL‐1β signaling, we investigated novel candidates that might play a role in activating the inflammasome pathway by infecting mouse bone marrow‐derived macrophages and human THP‐1 macrophage‐like cells with a panel of isogenic GAS mutant strains. We found that the cytolysins streptolysin O (SLO) and streptolysin S are the main drivers of IL‐1β release in proliferating logarithmic phase GAS. Using a mutant form of recombinant SLO, we confirmed that bacterial pore formation on host cell membranes is a key mechanism required for inflammasome activation. Our results suggest that streptolysins are major determinants of GAS‐induced inflammation and present an attractive target for therapeutic intervention.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22478181
Abstract: Supplementary data
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22478181.V1
Abstract: Supplementary data
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6529878
Abstract: AbstractPurpose: PI3K signaling is a common feature of B-cell neoplasms, including chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL), and PI3K inhibitors have been introduced into the clinic. However, there remains a clear need to develop new strategies to target PI3K signaling. PI3K activity is countered by Src homology domain 2-containing inositol-5′-phosphatase 1 (SHIP1) and, here, we have characterized the activity of a novel SHIP1 activator, AQX-435, in preclinical models of B-cell malignancies. Experimental Design: i In vitro /i activity of AQX-435 was evaluated using primary CLL cells and DLBCL-derived cell lines. i In vivo /i activity of AQX-435, alone or in combination with the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, was assessed using DLBCL cell line and patient-derived xenograft models. Results: Pharmacologic activation of SHIP1 using AQX-435 was sufficient to inhibit anti–IgM-induced PI3K-mediated signaling, including induction of AKT phosphorylation and MYC expression, without effects on upstream SYK phosphorylation. AQX-435 also cooperated with the BTK inhibitor ibrutinib to enhance inhibition of anti–IgM-induced AKT phosphorylation. AQX-435 induced caspase-dependent apoptosis of CLL cells preferentially as compared with normal B cells, and overcame i in vitro /i survival-promoting effects of microenvironmental stimuli. Finally, AQX-435 reduced AKT phosphorylation and growth of DLBCL i in vivo /i and cooperated with ibrutinib for tumor growth inhibition. Conclusions: Our results using AQX-435 demonstrate that SHIP1 activation may be an effective novel therapeutic strategy for treatment of B-cell neoplasms, alone or in combination with ibrutinib. /
Publisher: Hindawi Limited
Date: 30-06-2021
DOI: 10.1111/CMI.13373
Abstract: Group A Streptococcus (GAS) is a Gram-positive bacterial pathogen that causes significant morbidity and mortality worldwide. Recent clinical evidence suggests that the inflammatory marker interleukin-1β (IL-1β) plays an important role in GAS disease progression, and presents a potential target for therapeutic intervention. Interaction with GAS activates the host inflammasome pathway to stimulate production and secretion of IL-1β, but GAS can also stimulate IL-1β production in an inflammasome-independent manner. This review highlights progress that has been made in understanding the importance of host cell inflammasomes and IL-1 signalling in GAS disease, and explores challenges and unsolved problems in this host-pathogen interaction. TAKE AWAY: Inflammasome signalling during GAS infection is an emerging field of research. GAS modulates the NLRP3 inflammasome pathway through multiple mechanisms. SpeB contributes to IL-1β production independently of the inflammasome pathway. IL-1β signalling can be host-protective, but also drive severe GAS disease.
Publisher: University of Queensland Library
Date: 2023
DOI: 10.14264/1A77BE5
Publisher: American Association for Cancer Research (AACR)
Date: 04-2020
DOI: 10.1158/1078-0432.CCR-19-2202
Abstract: PI3K signaling is a common feature of B-cell neoplasms, including chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL), and PI3K inhibitors have been introduced into the clinic. However, there remains a clear need to develop new strategies to target PI3K signaling. PI3K activity is countered by Src homology domain 2-containing inositol-5′-phosphatase 1 (SHIP1) and, here, we have characterized the activity of a novel SHIP1 activator, AQX-435, in preclinical models of B-cell malignancies. In vitro activity of AQX-435 was evaluated using primary CLL cells and DLBCL-derived cell lines. In vivo activity of AQX-435, alone or in combination with the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, was assessed using DLBCL cell line and patient-derived xenograft models. Pharmacologic activation of SHIP1 using AQX-435 was sufficient to inhibit anti–IgM-induced PI3K-mediated signaling, including induction of AKT phosphorylation and MYC expression, without effects on upstream SYK phosphorylation. AQX-435 also cooperated with the BTK inhibitor ibrutinib to enhance inhibition of anti–IgM-induced AKT phosphorylation. AQX-435 induced caspase-dependent apoptosis of CLL cells preferentially as compared with normal B cells, and overcame in vitro survival-promoting effects of microenvironmental stimuli. Finally, AQX-435 reduced AKT phosphorylation and growth of DLBCL in vivo and cooperated with ibrutinib for tumor growth inhibition. Our results using AQX-435 demonstrate that SHIP1 activation may be an effective novel therapeutic strategy for treatment of B-cell neoplasms, alone or in combination with ibrutinib.
Publisher: Wiley
Date: 16-06-2021
Abstract: We still lack practical guidelines for ersifying cropping systems that consider both yield and regulating functions of agroecosystems. Recent studies have suggested that maximizing functional ersity (FD, the distribution of species with different functional traits in the niche space) may lead to agroecosystems with greater multifunctionality due to niche complementarity. Therefore, scientists are now advocating the use of a trait‐based approach to develop multifunctional sustainable agroecosystems. In order to assess the effects of crop FD on key agroecosystem functions and to consider trade‐offs and synergies among them, we established, in late 2016, permanent experimental field plots of successional agroforestry systems (SAFS), in humid subtropical Southern Brazil. The experiment represents a gradient of plant functional trait ersity (designed FD based on leaf nitrogen concentration), while maintaining crop species richness constant across all treatments. Our hypothesis is that the observed FD of crops (hereafter, crop FD) drives multiple agroecosystem functions. We determined the observed FD by quantifying traits of crops and weeds (maximum plant height, leaf area, specific leaf area) and performed two data collections (March and September 2017) at the end of the summer and winter crops respectively. We used structural equation modelling to test a hypothetical causal model to explain how crop FD affects three functions: weed suppression, soil protection (soil cover by either crops or weeds) and crop yield. Our results support the hypothesis that high crop FD drives agroecosystem processes and contributes to the provision of multiple ecosystem functions. We found that with greater crop FD in SAFS, crop plants occupied a large niche space, thereby increasing the total photosynthetic light intercepted in the agroecosystem, that in turn, increased crop yield. Additionally, greater FD increased soil protection by crops and decreased weed cover. This greater FD also reduced the FD of the weed community. Synthesis and applications . Crop mixtures based on complementary plant traits can increase the multifunctionality of agroecosystems through their sustainable use. A more heterogeneous structure and projection of crop leaf area drives greater resistance to competition with weeds and produces higher crop yields in young ersified crop mixtures.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6529878.V1
Abstract: AbstractPurpose: PI3K signaling is a common feature of B-cell neoplasms, including chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL), and PI3K inhibitors have been introduced into the clinic. However, there remains a clear need to develop new strategies to target PI3K signaling. PI3K activity is countered by Src homology domain 2-containing inositol-5′-phosphatase 1 (SHIP1) and, here, we have characterized the activity of a novel SHIP1 activator, AQX-435, in preclinical models of B-cell malignancies. Experimental Design: i In vitro /i activity of AQX-435 was evaluated using primary CLL cells and DLBCL-derived cell lines. i In vivo /i activity of AQX-435, alone or in combination with the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, was assessed using DLBCL cell line and patient-derived xenograft models. Results: Pharmacologic activation of SHIP1 using AQX-435 was sufficient to inhibit anti–IgM-induced PI3K-mediated signaling, including induction of AKT phosphorylation and MYC expression, without effects on upstream SYK phosphorylation. AQX-435 also cooperated with the BTK inhibitor ibrutinib to enhance inhibition of anti–IgM-induced AKT phosphorylation. AQX-435 induced caspase-dependent apoptosis of CLL cells preferentially as compared with normal B cells, and overcame i in vitro /i survival-promoting effects of microenvironmental stimuli. Finally, AQX-435 reduced AKT phosphorylation and growth of DLBCL i in vivo /i and cooperated with ibrutinib for tumor growth inhibition. Conclusions: Our results using AQX-435 demonstrate that SHIP1 activation may be an effective novel therapeutic strategy for treatment of B-cell neoplasms, alone or in combination with ibrutinib. /
No related grants have been discovered for Bill Shipley.