8 research outputs found
Replication Data for: Survey of Replication Data in AJPS, APSR, PQR, AJS, and ARP
No full textSurvey of Replication Data in AJPS (2012-2016), APSR (2012-2014), PRQ (2012-2016), AJS (2012-2014), and ARP (2012-2014)
Title, author(s), page numbers, issue and volume numbers are recorded for each article. Domestic in focus, empirical, a link to replication data, and an active (not "dead") link to replication data are all coded as 1. The links are then broken down by the type of website they link to. All links are provided
Replication Data for: Survey of Replication Data in AJPS, APSR, PQR, AJS, and ARP
No full textSurvey of Replication Data in AJPS (2012-2016), APSR (2012-2014), PRQ (2012-2016), AJS (2012-2014), and ARP (2012-2014)
Title, author(s), page numbers, issue and volume numbers are recorded for each article. Domestic in focus, empirical, a link to replication data, and an active (not "dead") link to replication data are all coded as 1. The links are then broken down by the type of website they link to. All links are provided
OTOH
No full textContains the essay “Unsettled Feelings". Funded by SSHRC Institutional Explore Grant. Design by Chloe Brumwell & Randy Lee Cutler.Unsettle
Engineering Conjugative Plasmids for Inducible Horizontal DNA Transfer
No full textRapidly developing microbial resistance to existing antimicrobials poses a growing threat to public health and global food security. Current chemical-based treatments target cells by inhibiting growth or metabolic function, but their effectiveness is diminishing. To address the growing antimicrobial resistance crisis, there is an urgent need for innovative therapies. Conjugative plasmids, a natural mechanism of horizontal gene transfer in bacteria, have been repurposed to deliver toxic genetic cargo to recipient cells, showing promise as next-generation antimicrobial agents. However, the ecological risks posed by unintended gene transfer require robust biocontainment strategies. In this study, we developed inducible conjugative plasmids to solve these challenges. Utilizing an arabinose-inducible promoter, we evaluated 13 plasmids with single essential gene deletions, identifying trbC and trbF as strong candidates for stringent regulation. These plasmids demonstrated inducibility in both cis and trans configurations, with induction resulting in up to a 5-log increase in conjugation efficiency compared to uninduced conditions. Although challenges such as reduced conjugation efficiency and promoter leakiness persist, this work establishes a foundation for the controlled transfer of plasmids, paving the way for safer and more effective antimicrobial technologies.The presentation of the authors' names and (or) special characters in the title of the pdf file of the accepted manuscript may differ slightly from what is displayed on the item page. The information in the pdf file of the accepted manuscript reflects the original submission by the author
A proteomics investigation of primary human articular chondrocyte isolation
No full text\ua9 2025 The Author(s). Objective: Human primary articular chondrocytes (hPACs) are routinely isolated from articular cartilage for pre-clinical OA research. Collagenase digest of tissue is an essential step, yet the impact of lengthy enzymatic incubation on the hPAC phenotype is unclear. We aimed to delineate this through proteomic analysis. Design: hPACs were isolated from human knee cartilage (n = 4) from patients undergoing total knee replacement. Collagenase treatment was performed with or without prior fixation of the tissue. Proteomes were quantified using LC-MS/MS. The Proteomic Ruler was employed to estimate protein copy numbers and cell protein masses. Significant differences in protein intensities were determined using paired t-testing and Benjamini-Hochberg correction. Proteomic data were integrated with existing transcriptomes (GSE217871) of hPACs and ground cartilage (ex vivo) RNA. Results: Following collagenase treatment, we identified 498 differentially expressed proteins (DEP) in the unfixed cells. We observed depletion of FOXO signaling and enrichment of ribosomal RNA processing, indicative of increased cell cycle progression. This was supported by depletion of cell cycle inhibitors including CDKN1C. Transcriptomic analysis identified 3937 differentially expressed genes (DEG), and a 53 % overlap in DEP and DEG. Propidium iodide staining did not identify significant differences in cell cycle between fixed and unfixed hPACs. Conclusions: We identified shifts in the proteome and transcriptome of hPACs following collagenase digest, supporting the use of tissue fixation before extracting nucleic acids for analysis where possible. Despite widespread expression changes, hPACs largely retain their chondrocyte phenotype. These datasets and analyses will serve as a valuable resource for the OA and cartilage research community
The role of TGF-β and epithelial-to mesenchymal transition in diabetic nephropathy
No full textTransforming Growth Factor-beta (TGF-β) is a pro-sclerotic cytokine widely associated with the development of fibrosis in diabetic nephropathy. Central to the underlying pathology of tubulointerstitial fibrosis is epithelial-to-mesenchymal transition (EMT), or the trans-differentiation of tubular epithelial cells into myofibroblasts. This process is accompanied by a number of key morphological and phenotypic changes culminating in detachment of cells from the tubular basement membrane and migration into the interstitium. Ultimately these cells reside as activated myofibroblasts and further exacerbate the state of fibrosis. A large body of evidence supports a role for TGF-β and downstream Smad signalling in the development and progression of renal fibrosis. Here we discuss a role for TGF-β as the principle effector in the development of renal fibrosis in diabetic nephropathy, focusing on the role of the TGF-β1 isoform and its downstream signalling intermediates, the Smad proteins. Specifically we review evidence for TGF-β1 induced EMT in both the proximal and distal regions of the nephron and describe potential therapeutic strategies that may target TGF-β1 activity
The regulation of type I collagen gene expression in stromal fibroblast by breast tumour cells
No full textIncludes abstract.Includes bibliographical references (leaves 110-135).Recent studies have revealed that interactions between tumour cells and the surrounding stroma play an important role in facilitating tumour growth and invasion. Stromal fibroblasts produce most of the extracellular matrix (ECM) components found in the stroma, including type I collagen. Previous in vivo studies in our laboratory have shown that type I collagen mRNA levels are decreased in stage II and III breast tumour tissue compared to adjacent normal tissue
