Irish Universities
Not a member yet
78452 research outputs found
Sort by
Association of genetic polymorphisms related to Johne’s disease with estimated breeding values of Holstein sires for milk ELISA test scores
No full textBackground: Johne’s disease (JD) is a chronic intestinal inflammatory disease caused by Mycobacterium avium
subsp. paratuberculosis (MAP) infection in ruminants. Since there are currently no effective vaccine or treatment
options available to control JD, genetic selection may be an alternative strategy to enhance JD resistance.
Numerous Single Nucleotide Polymorphisms (SNPs) have been reported to be associated with MAP infection status
based on published genome-wide association and candidate gene studies. The main objective of this study was to
validate these SNPs that were previously identified to be associated with JD by testing their effect on Holstein bulls’
estimated breeding values (EBVs) for milk ELISA test scores, an indirect indicator of MAP infection status in cattle.
Results: Three SNPs, rs41810662, rs41617133 and rs110225854, located on Bos taurus autosomes (BTA) 16, 23 and
26, respectively, were confirmed as significantly associated with Holstein bulls’ EBVs for milk ELISA test score (FDR <
0.01) based on General Quasi Likelihood Scoring analysis (GQLS) analysis. Single-SNP regression analysis identified
four SNPs that were associated with sire EBVs (FDR < 0.05). This includes two SNPs that were common with GQLS
(rs41810662 and rs41617133), with the other two SNPs being rs110494981 and rs136182707, located on BTA9 and
BTA16, respectively.
Conclusions: The findings of this study validate the association of SNPs with JD MAP infection status and highlight
the need to further investigate the genomic regions harboring these SNPs
Epidemiology of chronic lymphocytic leukaemia in an Irish subpopulation with total case ascertainment: an additional tool for health economic planning
No full textChronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL) is the commonest B-cell malignancy affecting Caucasians, with a variable national incidence depending on the ethnic composition and age profile of the population.1 The National Cancer Registry of Ireland (NCRI) quotes a Republic of Ireland (ROI) CLL incidence of 6·1/100 000, which appeared lower than our clinical experience indicated.2 Establishing accurate CLL incidence figures and numbers of patients requiring therapy would improve health service provision planning.
Chronic lymphocytic leukaemia is a clinically variable disease; up to one-third of patients are never treated, while ‘high-risk’ patients require costly, prolonged targeted therapy to circumvent chemoresistance.3-5 Although unmutated immunoglobulin variable heavy chain (IgVH), tumour protein p53 (TP53), splicing factor 3B subunit 1 (SF3B1), baculoviral IAP repeat-containing 3 (BIRC3) and Notch receptor 1 (NOTCH1) gene mutations confer inferior outcomes, the commonly used targeted therapies that include Bruton tyrosine kinase inhibitors such as ibrutinib and the B-cell lymphoma 2 (BCL2) inhibitor, venetoclax are only available for TP53-disrupted (mutation or deletion) and relapsed CLL.6, 7 The high cost of these drugs is challenging for healthcare budgeting because of the requirement for long-term treatment until toxicity/resistance and the potential for multiple targeted drug combinations.
The present study uses a subpopulation ‘complete ascertainment’ approach to define the incidence of CLL and the numbers of patients requiring treatment annually in the ROI, many of whom may benefit from targeted-therapy treatment in first and second line as being defined by recently completed or ongoing studies
Gamma-aminobutyric acid-producing lactobacilli positively affect metabolism and depressive-like behaviour in a mouse model of metabolic syndrome
No full textMetabolic and neuroactive metabolite production represents one of the mechanisms through which
the gut microbiota can impact health. One such metabolite, gamma-aminobutyric acid (GABA), can
modulate glucose homeostasis and alter behavioural patterns in the host. We previously demonstrated
that oral administration of GABA-producing Lactobacillus brevis DPC6108 has the potential to increase
levels of circulating insulin in healthy rats. Therefore, the objective of this study was to assess the
efcacy of endogenous microbial GABA production in improving metabolic and behavioural outcomes
in a mouse model of metabolic dysfunction. Diet-induced obese and metabolically dysfunctional
mice received one of two GABA-producing strains, L. brevis DPC6108 or L. brevis DSM32386, daily for
12 weeks. After 8 and 10 weeks of intervention, the behavioural and metabolic profles of the mice
were respectively assessed. Intervention with both L. brevis strains attenuated several abnormalities
associated with metabolic dysfunction, causing a reduction in the accumulation of mesenteric adipose
tissue, increased insulin secretion following glucose challenge, improved plasma cholesterol clearance
and reduced despair-like behaviour and basal corticosterone production during the forced swim test.
Taken together, this exploratory dataset indicates that intervention with GABA-producing lactobacilli
has the potential to improve metabolic and depressive- like behavioural abnormalities associated with
metabolic syndrome in mice
Experimental challenge with bovine respiratory syncytial virus in dairy calves: bronchial lymph node transcriptome response
No full textBovine Respiratory Disease (BRD) is the leading cause of mortality in calves. The objective of this study
was to examine the response of the host’s bronchial lymph node transcriptome to Bovine Respiratory
Syncytial Virus (BRSV) in a controlled viral challenge. Holstein-Friesian calves were either inoculated
with virus (103.5TCID50/ml×15ml) (n=12) or mock challenged with phosphate bufered saline (n=6).
Clinical signs were scored daily and blood was collected for haematology counts, until euthanasia at day
7 post-challenge. RNA was extracted and sequenced (75bp paired-end) from bronchial lymph nodes.
Sequence reads were aligned to the UMD3.1 bovine reference genome and diferential gene expression
analysis was performed using EdgeR. There was a clear separation between BRSV challenged and
control calves based on gene expression changes, despite an observed mild clinical manifestation
of the disease. Therefore, measuring host gene expression levels may be benefcial for the diagnosis
of subclinical BRD. There were 934 diferentially expressed genes (DEG) (p<0.05, FDR <0.1, fold
change >2) between the BRSV challenged and control calves. Over-represented gene ontology terms,
pathways and molecular functions, among the DEG, were associated with immune responses. The
top enriched pathways included interferon signaling, granzyme B signaling and pathogen pattern
recognition receptors, which are responsible for the cytotoxic responses necessary to eliminate the
virus
How can I improve my teaching of Wellbeing in my Senior Infant class?
No full textThe purpose of this self-study action research project is to establish how I can improve my
teaching of Wellbeing in my Senior Infant classroom. Wellbeing is an area that is evolving in
the education sector, for instance, by 2023, all primary schools must have a Wellbeing
Promotion Process (Department of Education 2018). Wellbeing is also present in the Draft
Primary Curriculum Framework (National Council for Curriculum and Assessment, 2020).
However, the need for wellbeing education became strikingly evident in my classroom as a
result of the Covid-19 Pandemic and school closures as children struggled to address their
emotions from this time. It became clear to me that the time to improve my wellbeing
education skills was now.
Throughout two action research cycles, I compared programme-based wellbeing
education to teacher-led wellbeing education. These six-week cycles took place in my Senior
Infant classroom, located in a DEIS, co-educational school in County Dublin. The
intervention displayed benefits and downfalls to both approaches to wellbeing education.
After analysing all data, the findings demonstrated that following a programme, but
tailoring it to meet the needs and experiences of the pupils in the class, was the best type of
practice for me in my setting. Following a programme ensures consistency when considering
a whole-school approach to wellbeing education. However, it is essential that the teacher is
confident in adapting these lessons to acknowledge arising circumstances in the class that
may not be covered in the course, such as bereavement, or response to a global pandemic
Development of gene therapies for retinal degenerations
No full textThe studies described in this thesis explore potential gene therapies for retinal degenerative diseases using adeno-associated virus (AAV) vectors for gene delivery.
Inherited retinal degenerations (IRDs) are a leading cause of vision loss for people of working age and exhibit extreme genetic heterogeneity, with over 270 known genes implicated. Retinitis pigmentosa (RP), a progressive rod-cone dystrophy, represents the most common IRD and can be caused by mutations in any of over 80 different genes. The research presented in Chapter 2 of this thesis relates to X-linked RP (XLRP) caused by mutation of the RP2 gene. Through a collaborative effort, retinal organoids (ROs) were used to model this form of XLRP. A novel early-onset rod degeneration phenotype emerged in RP2 null ROs, which could be prevented by highly efficient transduction with an AAV RP2 gene replacement vector. In Chapter 3, the feasibility of a gene editing-based treatment for rhodopsin-linked autosomal dominant RP (RHO-ADRP) was explored. A dual AAV CRISPR-Cas9 based platform was developed to test the efficiency of this strategy in photoreceptors of a humanised mouse model of RHO-ADRP.
Alongside the development of gene-specific treatment strategies for monogenic IRDs, there is also considerable interest in exploring gene-independent therapeutics that can modulate common degenerative mechanisms. Such strategies may circumvent the substantial genetic heterogeneity of IRDs and, moreover, be applicable to multifactorial ocular disorders. Of note, bioenergetic perturbation is emerging as a major underlying factor in diseases of the retina and optic nerve, including glaucoma the most common cause of irreversible blindness. The study presented in the final research chapter of this thesis examined whether modulating such features of disease, using an AAV gene therapy approach, could be beneficial in a glaucomatous context. When tested in a murine model of chronic ocular hypertension, retinal ganglion cell body density was significantly preserved in eyes treated with this gene therapy.
Overall, the data presented in this thesis support the immense potential of gene therapies for the treatment of monogenic and multifactorial retinal degenerations
‘How Can I Use Digital Technologies to Facilitate Cooperative Learning in my Classroom?’ A Self-Study Action Research Project Undertaken During a Global Pandemic
No full textIn the 2020-21 academic year, school closures and social distancing requirements had a profound impact on the way in which children learned and teachers taught. This self-study action research project explores how I attempted to address the constraints of a new, restrictive learning environment with an intervention that used digital technologies to facilitate cooperative learning in my 6th class classroom.
Using an array of digital tools including BookCreator, Stop Motion Studio and the full range of apps available on GSuite for Education, the 27 children in my class were asked to work in cooperative groups to complete an open-ended task; one in which they created a character from the future and detailed that character’s success in overcoming the challenges of living through a global pandemic.
Schools were closed for the first half of the intervention, while my pregnancy meant that I was forced to facilitate the second half from home. Consequently, the use of digital technologies was inextricably linked with the restrictions of the pandemic, and with all of their accompanying frustrations. Conscious that the intervention could not be examined separately to the context in which it took place, I focused not only on the affordances of digital tools to facilitate the cooperative learning process, but on the significance of the nature of the task and on the impact that the Covid-19 restrictions had on that same process.
Qualitative data was gathered from the written and oral reflections of my students and a group of four critical friends, as well as from my own observations and reflective journal. An analysis of this data led me to conclude that digital technologies could be used to
facilitate cooperative learning by supporting dialogue between group members and by offering a sense of autonomy to students. The motivation that dialogue and autonomy could generate proved especially important in the context of online learning and the socially distant classroom. The negative emotions fuelled by the restrictions of the pandemic were not, however, always counterbalanced by the affordances of digital tools or by the open-ended nature of the task; and children\u27s motivation often suffered due to a perceived lack of autonomy over various elements of the project.
These results have implications for my future practice and, indeed, for policy; suggesting that greater flexibility needs to feature in the classroom and curriculum alike. Importantly, my findings will allow me to live more closely to my values of student voice and autonomy. As I encourage children to express themselves with the aid of digital tools, I will continuously adjust my practice so as to promote a sense of autonomy; and successfully reap the long-proven benefits of cooperative learning
The Brontës, the Shelleys, Kingsley and Martin Amis: new research suggests literary relatives share similar writing styles
No full textNew research shows that literary relatives tend to share a similar writing style
Emerging out of the “blur”: exploration, evaluation and significance of 3D N-glycans’ structure through molecular dynamic studies
No full textGlycosylation is the most abundant and diverse post-translational modification of proteins, contributing
to protein folding, trafficking, structural stability and dynamics, and function. Complex N-glycans are
a class of glycans found in eukaryotes, sharing a common pentasaccharide core structure. The
functionalization of the arms and the branching patterns are specific to different species, while the
complexity of the cellular biosynthetic pathways contribute to the broad variety and to the heterogeneity
of N-glycan sequences. By understanding at an atomistic level of detail the structural implications of
glycan sequence, we can relate the glycan sequence to its function in a given glycoprotein environment.
With this ultimate goal in mind I conducted, through conventional and enhanced molecular dynamics
(MD) methods, a series of systematic studies of mammalian, plant and invertebrate glycosylation
patterns, in order to characterize the intrinsic 3D architecture of different sets of commonly found and
synthetic (non-natural) glycan structures. From these results, we were able to disentangle the
complexity of N-glycans structure and dynamics through a new 3D representation, which describes N-
glycans not only in terms of the monosaccharides sequence, but that also includes anomeric
configurations and linkage specificity. Within this framework, we defined N-glycans as structured by
specific groups of monosaccharide units, named “glycoblocks”. This formulation incorporates 3D
structural information and uniquely dictates the overall conformational landscape of any given N -
glycan.
With this expanded viewpoint of sequence-to-structure dependencies in complex N-glycans, we applie d
this knowledge to glycoproteins, where variation of glycan composition affects its functiona l
capabilities. In the two cases presented in this thesis, we determined how changes in the sequence of
the N-glycans in the Fc region of IgG1 antibodies affect its effector function, and discovered for the
first time a unique functional role of the glycan shield in the SARS-CoV-2 spike protein. In both cases,
we observed that the conformational equilibria of complex N-glycans change to promote conformers
that can accommodate interactions with the glycoprotein environment, but this adaption does not
interfere with the intrinsic 3D glycan architecture, shifting a paradigm commonly assumed in structural
biology, where the protein dictates the glycan conformation by actively morphing it.
The work presented in this thesis shows an alternative atomistic perspective of N-glycans structure and
dynamics, where glycans play a starring role rather than a cameo as a simple protein “decoration”, while
the knowledge and insight gained could inform the ad-hoc design and modulation of sequence-to-
structure-to-function relationships of complex N-glycans, with applications in glycoengineering and
therapeutic and diagnostic strategies
The Cabinet of Irish Literature: A Historical Perspective on Irish Anthologies
No full textTHE CABINET OF IRISH LITERATURE: A HISTORICAL PERSPECTIVE ON IRISH ANTHOLOGIES* MARGARET KELLEHER I. THE “CULTURE OF THE EXCERPT” among the flurry of reviews and commentaries that followed the publication of volumes I to III of the Field Day Anthology of Irish Writing in 1991, those of most enduring interest moved beyond the heat of the moment to a more general reflection on the role of anthologies themselves. Francis Mulhern’s 1993 essay, “A Nation, Yet Again” began, for example, with the cautionary pronouncement, by then all too evident, that “[a]nthologies are strategic weapons in literary politics.”1 Mulhern acknowledged that “authored texts of all kinds—poems, novels, plays, reviews, analyses—play more or less telling parts in a theatre of shifting alliances and antagonisms ,” but he argued for the special rhetorical force of anthologies in their “simulation of self evidence.THE CABINET OF IRISH LITERATURE: A HISTORICAL PERSPECTIVE ON IRISH ANTHOLOGIES* MARGARET KELLEHER I. THE “CULTURE OF THE EXCERPT” among the flurry of reviews and commentaries that followed the publication of volumes I to III of the Field Day Anthology of Irish Writing in 1991, those of most enduring interest moved beyond the heat of the moment to a more general reflection on the role of anthologies themselves. Francis Mulhern’s 1993 essay, “A Nation, Yet Again” began, for example, with the cautionary pronouncement, by then all too evident, that “[a]nthologies are strategic weapons in literary politics.”1 Mulhern acknowledged that “authored texts of all kinds—poems, novels, plays, reviews, analyses—play more or less telling parts in a theatre of shifting alliances and antagonisms ,” but he argued for the special rhetorical force of anthologies in their “simulation of self evidence.THE CABINET OF IRISH LITERATURE: A HISTORICAL PERSPECTIVE ON IRISH ANTHOLOGIES* MARGARET KELLEHER I. THE “CULTURE OF THE EXCERPT” among the flurry of reviews and commentaries that followed the publication of volumes I to III of the Field Day Anthology of Irish Writing in 1991, those of most enduring interest moved beyond the heat of the moment to a more general reflection on the role of anthologies themselves. Francis Mulhern’s 1993 essay, “A Nation, Yet Again” began, for example, with the cautionary pronouncement, by then all too evident, that “[a]nthologies are strategic weapons in literary politics.”1 Mulhern acknowledged that “authored texts of all kinds—poems, novels, plays, reviews, analyses—play more or less telling parts in a theatre of shifting alliances and antagonisms ,” but he argued for the special rhetorical force of anthologies in their “simulation of self evidence