ORCID Profile
0000-0002-5109-3222
Current Organisation
University of South Australia
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Publisher: JMIR Publications Inc.
Date: 14-03-2023
Abstract: he delivery of education about pain neuroscience and the evidence for different treatment approaches has become a key component of contemporary persistent pain management. Chatbots, or more formally conversation agents, are increasingly being used in health care settings due to their versatility to provide interactive and in idualized approaches to both capture and deliver information. Research focused on the acceptability of erse chatbot formats can assist in developing a better understanding of the education needs of target populations and maximize the impact of these software applications within the health field. his study aimed to 1) detail the development and initial pilot testing of a multi-modality pain education chatbot (Dolores) that can be utilized across different age groups, and 2) investigate if acceptability and feedback was comparable across age groups following pilot testing. ollowing an initial design phase involving software engineers (n=2) and expert clinicians (n=6), 60 in iduals with chronic pain who attended an outpatient clinic at one of two pain centers in Australia were recruited for pilot testing. Twenty adolescents (10-18 years), 20 young adults (19-35 years), and 20 adults (over 35 years of age) with persistent pain were recruited. Participations were given an iPad with the Dolores app installed and spent 20-30 minutes completing interactive chatbot activities to: i) gather a pain history and ii) provide education about pain and pain treatments. After the chatbot activities, participants completed a custom-made feedback questionnaire measuring acceptability constructs pertaining to health education chatbots. To determine the effect of age group on acceptability ratings and feedback provided, a series of binomial logistic regression models and cumulative odds ordinal logistic regression models with proportional odds were then generated. verall, acceptability was high for the following constructs: engagement, perceived value, usability, accuracy, responsiveness, adoption intention, aesthetics and overall quality. The effect of age group on all acceptability ratings was small and not statistically significant. Analysis of open-ended question responses revealed that major frustrations with the app were related to Dolores’ speech which was explored further through a comparative analysis. For providing negative feedback about Dolores’ speech, a logistic regression model showed that the effect of age group was statistically significant (χ2(2) = 11.68, P = .003) and explained 27.1% of the variance (Nagelkerke R2). Adults and young adults were less likely to comment on Dolores’ speech compared to adolescent participants (OR=0.20, 95% CI [0.05, 0.84] OR=0.05, 95% CI [0.01, 0.43] respectively). Comments related to both speech rate (too slow) and quality (unpleasant and robotic). his study provided support for the acceptability of pain history and education chatbots across different age groups. Chatbot acceptability for adolescent cohorts may be improved by enabling self-selection of speech characteristics such as rate and personable tone.
Publisher: Springer Science and Business Media LLC
Date: 19-04-2022
DOI: 10.1038/S41467-022-29660-3
Abstract: The ubiquitin ligase NEDD4 promotes neural crest cell (NCC) survival and stem-cell like properties to regulate craniofacial and peripheral nervous system development. However, how ubiquitination and NEDD4 control NCC development remains unknown. Here we combine quantitative analysis of the proteome, transcriptome and ubiquitinome to identify key developmental signalling pathways that are regulated by NEDD4. We report 276 NEDD4 targets in NCCs and show that loss of NEDD4 leads to a pronounced global reduction in specific ubiquitin lysine linkages. We further show that NEDD4 contributes to the regulation of the NCC actin cytoskeleton by controlling ubiquitination and turnover of Profilin 1 to modulate filamentous actin polymerization. Taken together, our data provide insights into how NEDD4-mediated ubiquitination coordinates key regulatory processes during NCC development.
Publisher: MDPI AG
Date: 20-07-2021
DOI: 10.3390/IJMS22147760
Abstract: The importance of lymphatic vessels in a myriad of human diseases is rapidly gaining recognition lymphatic vessel dysfunction is a feature of disorders including congenital lymphatic anomalies, primary lymphoedema and obesity, while improved lymphatic vessel function increases the efficacy of immunotherapy for cancer and neurological disease and promotes cardiac repair following myocardial infarction. Understanding how the growth and function of lymphatic vessels is precisely regulated therefore stands to inform the development of novel therapeutics applicable to a wide range of human diseases. Lymphatic vascular development is initiated during embryogenesis following establishment of the major blood vessels and the onset of blood flow. Lymphatic endothelial progenitor cells arise from a combination of venous and non-venous sources to generate the initial lymphatic vascular structures in the vertebrate embryo, which are then further ramified and remodelled to elaborate an extensive lymphatic vascular network. Signalling mediated via vascular endothelial growth factor (VEGF) family members and vascular endothelial growth factor receptor (VEGFR) tyrosine kinases is crucial for development of both the blood and lymphatic vascular networks, though distinct components are utilised to different degrees in each vascular compartment. Although much is known about the regulation of VEGFA/VEGFR2 signalling in the blood vasculature, less is understood regarding the mechanisms by which VEGFC/VEGFD/VEGFR3 signalling is regulated during lymphatic vascular development. This review will focus on recent advances in our understanding of the cellular and molecular mechanisms regulating VEGFA-, VEGFC- and VEGFD-mediated signalling via VEGFRs which are important for driving the construction of lymphatic vessels during development and disease.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 18-08-2023
Abstract: Piezo channels are critical cellular sensors of mechanical forces. Despite their large size, ubiquitous expression, and irreplaceable roles in an ever-growing list of physiological processes, few Piezo channel–binding proteins have emerged. In this work, we found that MyoD (myoblast determination)–family inhibitor proteins (MDFIC and MDFI) are PIEZO1/2 interacting partners. These transcriptional regulators bind to PIEZO1/2 channels, regulating channel inactivation. Using single-particle cryogenic electron microscopy, we mapped the interaction site in MDFIC to a lipidated, C-terminal helix that inserts laterally into the PIEZO1 pore module. These Piezo-interacting proteins fit all the criteria for auxiliary subunits, contribute to explaining the vastly different gating kinetics of endogenous Piezo channels observed in many cell types, and elucidate mechanisms potentially involved in human lymphatic vascular disease.
Publisher: Public Library of Science (PLoS)
Date: 06-07-2012
Publisher: JMIR Publications Inc.
Date: 06-10-2023
DOI: 10.2196/47267
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1016/J.YDBIO.2013.09.024
Abstract: The integration of multiple morphogenic signalling pathways and transcription factor networks is essential to mediate neural crest (NC) cell induction, delamination, survival, stem-cell properties, fate choice and differentiation. Although the transcriptional control of NC development is well documented in mammals, the role of post-transcriptional modifications, and in particular ubiquitination, has not been explored. Here we report an essential role for the ubiquitin ligase Nedd4 in cranial NC cell development. Our analysis of Nedd4(-/-) embryos identified profound deficiency of cranial NC cells in the absence of structural defects in the neural tube. Nedd4 is expressed in migrating cranial NC cells and was found to positively regulate expression of the NC transcription factors Sox9, Sox10 and FoxD3. We found that in the absence of these factors, a subset of cranial NC cells undergo apoptosis. In accordance with a lack of cranial NC cells, Nedd4(-/-) embryos have deficiency of the trigeminal ganglia, NC derived bone and malformation of the craniofacial skeleton. Our analyses therefore uncover an essential role for Nedd4 in a subset of cranial NC cells and highlight E3 ubiquitin ligases as a likely point of convergence for multiple NC signalling pathways and transcription factor networks.
Publisher: American Society for Clinical Investigation
Date: 18-05-2020
DOI: 10.1172/JCI99027
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.DEVCEL.2019.03.017
Abstract: The correct assignment of cell fate within fields of multipotent progenitors is essential for accurate tissue ersification. The first lymphatic vessels arise from pre-existing veins after venous endothelial cells become specified as lymphatic progenitors. Prox1 specifies lymphatic fate and labels these progenitors however, the mechanisms restricting Prox1 expression and limiting the progenitor pool remain unknown. We identified a zebrafish mutant that displayed premature, expanded, and prolonged lymphatic specification. The gene responsible encodes the regulator of alternative splicing, Nova2. In zebrafish and human endothelial cells, Nova2 selectively regulates pre-mRNA splicing for components of signaling pathways and phosphoproteins. Nova2-deficient endothelial cells display increased Mapk/Erk signaling, and Prox1 expression is dynamically controlled by Erk signaling. We identify a mechanism whereby Nova2-regulated splicing constrains Erk signaling, thus limiting lymphatic progenitor cell specification. This identifies the capacity of a factor that tunes mRNA splicing to control assignment of cell fate during vascular differentiation.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 02-03-2022
DOI: 10.1126/SCITRANSLMED.ABM4869
Abstract: Central conducting lymphatic anomaly (CCLA), characterized by the dysfunction of core collecting lymphatic vessels including the thoracic duct and cisterna chyli, and presenting as chylothorax, pleural effusions, chylous ascites, and lymphedema, is a severe disorder often resulting in fetal or perinatal demise. Although pathogenic variants in RAS/mitogen activated protein kinase (MAPK) signaling pathway components have been documented in some patients with CCLA, the genetic etiology of the disorder remains uncharacterized in most cases. Here, we identified biallelic pathogenic variants in MDFIC , encoding the MyoD family inhibitor domain containing protein, in seven in iduals with CCLA from six independent families. Clinical manifestations of affected fetuses and children included nonimmune hydrops fetalis (NIHF), pleural and pericardial effusions, and lymphedema. Generation of a mouse model of human MDFIC truncation variants revealed that homozygous mutant mice died perinatally exhibiting chylothorax. The lymphatic vasculature of homozygous Mdfic mutant mice was profoundly mispatterned and exhibited major defects in lymphatic vessel valve development. Mechanistically, we determined that MDFIC controls collective cell migration, an important early event during the formation of lymphatic vessel valves, by regulating integrin β 1 activation and the interaction between lymphatic endothelial cells and their surrounding extracellular matrix. Our work identifies MDFIC variants underlying human lymphatic disease and reveals a crucial, previously unrecognized role for MDFIC in the lymphatic vasculature. Ultimately, understanding the genetic and mechanistic basis of CCLA will facilitate the development and implementation of new therapeutic approaches to effectively treat this complex disease.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 13-12-2012
Location: No location found
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Genevieve Secker.