NUI Maynooth Eprint Archive
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Responsive Synthetic Peptide Conjugates – From Sensors to Peptidomimetics
No full textThe importance of luminescent peptide sensors and peptidomimetics lies in their ability to address challenges in detection, imaging, drug development, and various other fields. More specifically, luminescent peptide-conjugates are often biocompatible and can detect analytes at trace-levels. This makes them effective tools for the visualisation of cellular processes and molecular interactions, while aiding in early diagnosis and monitoring disease progression. Indeed, peptidomimetics are designed to mimic the biological activity of peptides while often offering enhanced stability and bioavailability, overcoming some of the many limitations associated with native peptides. This thesis will focus on the use of modified synthetic peptide-conjugates as potential luminescent sensors for the visualisation of Caspase-3, and the design of a completely new peptidomimetic-scaffold based on Squaratides – a hybrid mix of squaramides and peptides.
The thesis opens with a literature review (Chapter 1) documenting the therapeutic history of peptides and the inherent functionalities that facilitate their diverse chemistries, all the way up to the luminescent applications of peptide-conjugates for selective sensing/visualisation of specific disease-related enzymes. Chapter 2 details the design, synthesis, and characterisation of a ratiometric fluorescent caspase-3 probe. This novel peptide-conjugate was investigated as a potential probe for the visualisation of caspase-3 via UV-vis/Fluorescence studies, enzyme kinetic(s) experiments, and selectivity studies. The probe was shown to be highly selective towards caspase-3, with kinetic data comparable to others reported in literature, while benefiting from the advantages of ratiometric detection. The design of a potential red-emitting naphthalimide-peptide probe for caspase-3 visualisation is also discussed.
Chapter 3 aims to build on the idea of fluorescent visualisation using traditional organic fluorophores, but instead employs lanthanide luminescence, with their prolonged luminescence lifetimes and tuneable emission colours. This chapter reports the synthesis and characterisation of a family of novel, water-soluble squaramide-based cyclen ligands with varying symmetry and substitution patterns, including one ligand that may have the potential to act as a lanthanide-based caspase-3 probe. The photophysical properties of each squaramide
antenna was investigated, with preliminary metal-centred luminescence emission spectra being obtained for Eu3+ and Tb3+ complexes.
The final section (Chapter 4) documents the attempted synthesis of a novel class of peptidomimetics featuring a squaramide motif. The aim was to investigate the use of squaramides as potential peptidomimetics, by generating synthetic analogues of a previous pharmaceutical drug – Cilengitide – with the hope of improving its overall stability. This chapter outlines a versatile synthetic methodology for the production of Nβ-Fmoc alkyl-amines (from their respective commercially available amino acids) and their incorporation into cyclic Squaratide peptidomimetics
A noisy-input generalized additive model for relative sea-level change along the Atlantic coast of North America
No full textWe propose a Bayesian, noisy-input, spatial–temporal generalized additive model to examine regional relative sea-level (RSL) changes over time. The model provides probabilistic estimates of component drivers of regional RSL change via the combination of a univariate spline capturing a common regional signal over time, random slopes and intercepts capturing site-specific (local), long-term linear trends and a spatial– temporal spline capturing residual, non-linear, local variations. Proxy and instrumental records of RSL and corresponding measurement errors inform the model and a noisy-input method accounts for proxy temporal uncertainties. Results highlight the decomposition of regional RSL changes over 3,000 years along North America’s Atlantic coast. The physical process glacial isostatic adjustment prevailed before 1800 CE, with anthropogenic forcing dominating after 1900 CE
Restorative circles for police-community dialogue: a facilitation script from the UBUNTU Project in Dublin, Ireland
No full textFew have used restorative practices to structure police-community engagement.
Fewer, still, have published their script after doing so, enabling others to use or
learn from it. This paper presents and explains a script that the authors devised
and used to facilitate a two-day dialogue process between six Gardaí (Irish police
officers) and six young Black adults in Blanchardstown, Dublin, Ireland.
Drawing on literature from the fields of restorative practices and dialogue, the
paper recounts the four stages of the process delivered. It started by 1) establishing relationships, common intentions and norms, before the participants
shared and explored their experiences and perceptions of 2) Blanchardstown and
belonging, 3) policing, and 4) the future.
The article explains the context in which the project and dialogue process took
place, before providing an annotated script to outline the questions asked and
activities undertaken, and explain their rationale. The dialogue process was co-designed by the project lead (Marder), project researcher (Kurz) and young Black
adults and police who received restorative practices training, including one person
from each who, with Marder, co-facilitated the dialogue (Ibeanu, O’Neill)
Population dynamics of mushroom casing over the course of Agaricus bisporus cultivation in the presence of Bacillus velezensis QST 713 and Bacillus velezensis Kos biocontrol agents
No full textThe globally cultivated white button mushroom (Agaricus bisporus) is grown commercially at an industrial scale. Numerous pathogens pose a significant economic threat to its cultivation. Due to the emergence of resistance towards fungicide treatments, the future of mushroom disease treatment will need to move towards integrated pest management including the use of biological control agents (BCAs). In this study, we investigated the impact of the BCAs, B. velezensis QST 713 and Kos on the population dynamics of the microbiota of mushroom casing. Amplicon sequencing revealed that four Bacterial phyla Firmicutes, Proteobacteria, Bacteroidota and Actinobacteriota dominated at casing and the end of the crop cycle. The most dominant fungal genus detected at casing was Agaricus and after 7 days accounted for the vast majority of fungal species detected. The application of BCAs, B. velezensis QST 713 and B. velezensis Kos did not have a significant impact on the microbiota across the crop cycle and comparisons between control plots and plots treated with BCA showed no significant differences in their microbiome composition. This research contributes novel insights into the dynamics, composition, and structure of microbial communities within A. bisporus mushroom casing with and without the application of two BCAs
Qualitative research during the COVID19 pandemic: the impact of remote research on the collaborative production of methodological knowledge
No full textDuring the COVID19 crisis, school closure was a frequent feature of Government responses. The Children’s School Lives (CSL) national cohort study of primary schooling in Ireland had to be adapted and transferred online as an interim response to the unprecedented impact that the pandemic had on the research environment. Adapting longitudinal qualitative research in response to a global pandemic brought specific challenges. In addition to moving data collection to remote methods, longitudinal studies also needed to maintain a focus on retention of research participants and sustain an analysis that informs the longitudinal design of the study. Based on reflective research practice during the COVID19 pandemic and through the collaborative production of methodological knowledge, this paper contributes to the literature on remote research during times of crisis. However, it also extends this literature as the methodological learning can be applied beyond the very particular circumstances of a pandemic
What does well-being mean to me?’. Conceptualisations of well-being in Irish Primary Schooling
No full textPurpose
The purpose of this study is to understand the meaning of the term well-being as conceptualised by parents, grandparents, principals and teachers in the Irish primary education system.
Design/methodology/approach
A hermeneutic phenomenological approach was adopted to understand the nature and meaning of the phenomenon of well-being. Interviews were carried out with 54 principals, teachers, parents and grandparents from a representative sample of primary schools in Ireland. Each participant was asked the same, open, question: “What does well-being mean to you?” Responses were transcribed verbatim and analysed using a combination of the principles of the hermeneutic circle and Braun and Clarke’s framework for thematic analysis.
Findings
Three conceptualisations of well-being were identified (1) well-being is about being happy, (2) well-being is about being healthy and safe and (3) well-being is something you “do”.
Originality/value
To the best of our knowledge this paper is the first of its kind to describe how well-being is conceptualised by adults in Irish primary school contexts. In particular it highlights how neoliberal conceptualisations of well-being as a “thing”, a commodity exchanged on assumptions of individualism, moralism and bio-economism, have crept into the education of our youngest citizens
Looking beyond relative age to understand relative advantage and disadvantage in talent development
No full textIn this perspective article, we argue for a broader consideration of relative advantages and disadvantages in youth sport; a lens that considers the complex biopsychosocial factors that influence athlete development beyond relative age. We begin with a brief overview of Relative Age Effects (RAEs), with a particular focus on the proposed underlying mechanisms, followed by a discussion of the cultural and organisational considerations and implications that talent systems must consider when implementing interventions to counteract RAEs. We conclude by proposing key directions for future research in respect to RAEs and talent development more broadly. We argue that there is a need to consider the highly complex nature of RAEs, but also that there are no clear solutions to the issue of RAEs in youth sports, and that proposed solutions may come with unintended consequences. This should encourage us to experiment more, not less, with diverse ways of providing meaningful sports experiences that promote learning, psychosocial development, and performance. We suggest an urgent need for greater practical and research focus on supporting coaches, as they have the greatest capacity to understand the needs of individual athletes. In addition, systemically working towards equal access to skilful coaches. We encourage a shift in focus beyond descriptive methodologies of RAEs toward transformative research methodologies that include action-based research, complex interventions that incorporate context-sensitive qualitative methods, and other participatory research approaches
Mesenchymal stromal cells dampen trained immunity in house dust mite-primed macrophages expressing human macrophage migration inhibitory factor polymorphism
No full textBackground: Trained immunity results in long-term immunological memory, provoking a faster and greater
immune response when innate immune cells encounter a secondary, often heterologous, stimulus. We have
previously shown that house dust mite (HDM)-induced innate training is amplified in mice expressing the
human macrophage migration inhibitory factor (MIF) CATT7 functional polymorphism.
Aim: This study investigated the ability of mesenchymal stromal cells (MSCs) to modulate MIF-driven trained
immunity both in vitro and in vivo.
Methods: Compared with wild-type mice, in vivo HDM-primed bone marrow-derived macrophages (BMDMs)
from CATT7 mice expressed significantly higher levels of M1-associated genes following lipopolysaccharide stimulation ex vivo. Co-cultures of CATT7 BMDMs with MSCs suppressed this HDM-primed effect, with tumor necrosis factor alpha (TNF-a) being significantly decreased in a cyclooxygenase 2 (COX-2)-dependent manner.
Interestingly, interleukin 6 (IL-6) was suppressed by MSCs independently of COX-2. In an in vitro training assay,
MSCs significantly abrogated the enhanced production of pro-inflammatory cytokines by HDM-trained CATT7
BMDMs when co-cultured at the time of HDM stimulus on day 0, displaying their therapeutic efficacy in modulating an overzealous human MIF-dependent immune response. Utilizing an in vivo model of HDM-induced
trained immunity, MSCs administered systemically on day 10 and day 11 suppressed this trained phenomenon
by significantly reducing TNF-a and reducing IL-6 and C-C motif chemokine ligand 17 (CCL17) production.
Conclusions: This novel study elucidates how MSCs can attenuate an MIF-driven, HDM-trained response in
CATT7 mice in a model of allergic airway inflammatio
Trending extinctions: online interest in recently extinct animals
No full textHalf of all species are predicted to face extinction by the end of the century. Despite this, awareness of certain species' extinctions remains surprisingly muted, highlighting the need to improve and quantify public awareness. We explore the connection between biodiversity loss and public awareness by quantifying the changes in online interest on Twitter (now known as X) and Wikipedia both before and after the extinctions of eight species and following their reclassification in the IUCN Red List. Our findings reveal that extinction announcements generally spike online interest for most species, albeit briefly on Twitter (i.e. tweets and retweets about species), while Wikipedia (i.e. article pageviews of species) exhibits a more prolonged interest. IUCN reports were generally not associated with increased interest. Coordinated media coverage, especially when aligned with broader environmental narratives and key events, enhanced the impact of extinction announcements. On Twitter, spatially we observed a shift from local to global interest of users following extinction. We also found a small subset of influential users on Twitter, including content creators and media organisations, who disproportionately shaped conservation discussions. Environmentally oriented individuals and organisations also play a significant role, collectively comprising a third of the top retweeted users. Overall, these results highlight the need for conservation bodies, such as the IUCN, to engage more directly both with media organisations and content creators in order to drive public interest for conservation efforts, especially for less charismatic species. The tragedy of species extinction necessitates such efforts to ensure sustained and meaningful public awareness. Our findings also show that while social media outlets can generate global interest quickly, which may drive public discussions regarding ongoing extinctions and potential future de-extinctions, this is likely to be short-lived, underscoring the importance of alternative platforms such as Wikipedia, which can foster longer-term engagement
UNITES Project: Stakeholder Views and Experiences of Home Visiting in Ireland. Report Number Two
No full textNational policies such as Better Outcomes, Brighter Futures (2015), First 5 – A Whole of Government Strategy for Parents and Babies (2019) and Supporting Parents: A National Model of Parenting Support (2022), recognise the importance of, and reflect a strong and enduring commitment to, supporting early childhood development and wellbeing through the provision of accessible, high quality and evidence-led supports. For instance, a key goal of ‘First 5’ is to develop strong and supportive families and communities, including a commitment to the development of universal parenting supports (also reiterated in the National Model of Parenting Support Services) and, importantly, in the context of the current study, an evidence-led approach to home visiting services across a continuum of need (DCEDIY, 2022). Indeed, a wealth of both national and international evidence indicates that the home environment, and therefore services provided in the home, provide a crucially important context, and support, for healthy child development and wellbeing (e.g. Bradley & Corwyn, 2008).
The UNITES project: Aims and Objectives
The UNITES project was commissioned (in 2022) by the Department of Children Equality Disability Integration and Youth (DCEDIY). The project involved two separate, but related stages, the aims of which were: (1) to profile and critically review home visiting provision in Ireland; and (2) to elicit the insights, views and experiences of a wide range of stakeholders involved in managing, implementing, delivering or receiving home visiting programmes and services across the country. The ultimate goal of this work was to identify some proposed actions or ‘options’ that provide key stepping stones toward a more standardised
and sustainable ‘model’ of home visiting service delivery in Ireland