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Positioning the views of children with developmental disabilities at the centre of early interventions
No full textIncluding children who are neurodiverse in research and in practice is a necessity. This chapter considers why it is important that health and social care professionals foreground the voice of young children in family-centred practice. This chapter also contributes to our understanding of family-centred practice by focusing on the child’s view by drawing from seven studies involving preschool children with developmental disabilities. This chapter aims to extend a discourse that acknowledgement of a child’s perspective will create new priorities for everyone involved and allow interventions to be both functional and inclusive
Cara nó namhaid? An intleacht shaorga ghiniúnach agus oideolaíocht na Gaeilge ag leibhéal an ardoideachais.
No full textTá dúshláin shainiúla ag baint le húsáid na hIntleachta Saorga Ghiniúnaí (ISG) sa seomra ranga Gaeilge ag aon leibhéal oideachais. Faoi mar a mhíníonn Ní Chiaráin et al., (2023) thíos dúinn, meastar go forleathan gur radacach an rud é an ISG i réimse an oideachais trí chéile, ach is minic nach dtuigtear na himpleachtaí nó na dúshláin a eascraíonn ón gcineál seo teicneolaíochta sa ghnáthphobal, cé go bhfuil ‘súil an domhain mhóir’ ar an gcineál seo teicneolaíochta:
I gcás na dteangacha atá ar bheagán acmhainní digiteacha, an Ghaeilge ina measc, tá ceisteanna breise le cur san áireamh, mar shampla, tacair theoranta sonraí chun samhlacha iontaofacha teanga / acústaice a thraenáil, agus easpa taighdeoirí leis na scileanna cuí teangeolaíochta, teagaisc agus teicneolaíochta chun na córais a fhorbairt. Ciallaíonn an bhéim atá ar ollsonraíocht sna modhanna nua-aimseartha forbartha go bhfuil sé i bhfad níos deacra córais theagaisc a fhorbairt do theangacha neamhfhorleathana ná mar atá do na mórtheangacha (Ní Chiaráin et al., 2023: 5)peer-reviewe
An mhuc dhraíochta
No full textBhí Rí ann tráth a raibh triúr iníonacha aige. Tháinig an lá a raibh ar an Rí dul chun troda, mar sin chuir sé fios ar a iníonacha agus dúirt sé leo:
‘A chailíní, caithfidh mé dul chun cogaidh. Tá arm mór an namhad ar an mbealach. Is údar mór bróin dom é sibh a fhágáil, ach tabharfaidh sibh aire díobh féin agus mé imithe. Bígí go maith, agus tugaigí aire don teach. Féadfaidh sibh dul ag siúl sa ghairdín agus beidh cead bhur gcoise agaibh sa phálás, seachas an t-aon seomra amháin ar chúl ar an taobh thuaidh. Ná téigí isteach ansin ar bhur mbeo; ní fios cén dochar a dhéanfaí daoibh.’peer-reviewe
Making and breaking supramolecular synthons for modular protein frameworks
No full textAnionic calixarenes are useful mediators of protein assembly. In some cases, protein – calixarene cocrystallization yields multiple polymorphs. Ralstonia solanacearum lectin (RSL) cocrystallizes with p-sulfonato-calix[8]arene (sclx8) in at least four distinct pH-dependent arrangements. One of these polymorphs, occurring at pH ≤ 4, is a cubic framework in which RSL nodes are connected by sclx8 dimers. These dimers are supramolecular synthons that occur in distinct crystal structures. Now, we show that the discus-shaped dimer of p-phosphonato-calix[6]arene (pclx6), can replace the sclx8 dimer yielding a new assembly of RSL. Remarkably, just one type of RSL – pclx6 cocrystal was formed, irrespective of pH or crystallization condition. These results with pclx6 contrast starkly with sclx8 and suggest that the calixarene type (e.g., phosphonate versus sulfonate) dictates the synthon durability, which in turn exerts control over protein assembly and polymorph selection. Breaking the pclx6 dimer required a mutant of RSL with an affinity tag for macrocycle binding. This highly accessible, dicationic site resulted in a significantly altered and porous framework with pclx6 (but not with sclx8). Experiments with ternary mixtures of RSL, pclx6, and sclx8 provide evidence of pH-driven self-sorting. Thus, the “mix-and-match” of protein and supramolecular synthons is a promising approach to protein crystal engineering.The authors thank the University of Galway, the Irish Research Council (Government of Ireland postgraduate scholarship GOIPG/2021/333 to NMM), the Australian Research Council (DP1092810 grant to CLR), and Science Foundation Ireland (12/RC/2275_P2 and 13/CDA/2168) for funding. The authors thank SOLEIL synchrotron (Paris) for beam time allocation and the staff at beam line PROXIMA-2A (proposal # 20210974) for their assistance with data collection. The authors acknowledge the technical assistance of R. Doohan. An early version of this work was presented at the RSC Macrocyclic and Supramolecular Chemistry (MASC) meeting in Nottingham, in December 2022.peer-reviewe
Climate media amidst technopolitical change: challenges, transformations, and new directions for research
No full textIn this essay, we seek to provide a meta-level view of research on mediated climate change communication, taking stock of its achievements, historical and contemporary challenges, and future directions. While existing climate media scholarship has generated important insights to guide research and practice, recent empirical developments and technopolitical transformations challenge the traditional structure of climate media research. Historically, this research developed a tripartite structure where scholars have tended to focus on one of three distinct phases of the mediated communication process: (1) the production of narratives, frames, images, and other forms of communication about climate change; (2) the content and dissemination of these communication artifacts by and across media industries and institutions; and (3) these artifacts’ reception by and effects on policymakers, partisans, and publics. However, recent developments in communication technologies, media ecosystems, and the broader political landscape—including the increasing importance of social media and AI, new forms of climate obstruction, and rising antidemocratic forces across borders—have made these traditional lines of demarcation increasingly unworkable. While the lines of demarcation between production, dissemination, and reception are increasingly blurred in important new empirical phenomena, each has remained central in many scholarly works and the development of research questions. This persistence of the tripartite model, we argue, has caused climate media research to be slow to reflect the shifting dynamics of mediated climate communication today. After describing and analyzing the structural challenges that make doing more comprehensive climate media research so challenging, we conclude with proposals for new directions for scholarship that can help future research more fully contend with recent technopolitical transformations and move towards actionable research that is capable of grappling with and motivating robust responses to the complexities of climate change amid mounting authoritarian threats.
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Dathú Éadaigh
No full textPléifear dathú éadaigh san aiste seo, le béim speisialta ar dhathanna nádúrtha. Pléitear gnéithe den phróiseas ina ndéantaí éadach a dhathú go traidisiúnta. Pléifear cuid de na dathanna éagsúla agus conas mar a cruthaíodh iad. Baineadh úsáid as ábhar nádúrtha cosúil le glasraí agus plandaí agus ábhair eile nach iad mar chuid den phróiseas seo. Cuirfear san áireamh réimse leathan foinsí ó bhailiúcháin bhéaloidis go leabhair ar an ábhar.peer-reviewe
Mechano-dysfunction of Purkinje cells in Ataxia telangiectasia patients
No full textAtaxia telangiectasia (A-T) is a cerebellar ataxia caused by mutations in the ATM gene, leading to the progressive loss of Purkinje cells, though the mechanisms underlying this cell death are still largely unknown. While ATM is mainly recognized as a DNA damage response protein, it also plays a crucial role in many other cellular processes. Recently, it has emerged as a regulator of mechanotransduction. Using immunofluorescence, Brillouin microscopy, and laser microdissection proteomics, we investigated how mechanical dysfunction contributes to the degeneration of Purkinje cells in A-T patients. We found that Purkinje cell nuclei exhibit unique mechanical and elastic properties, making them especially vulnerable to chromatin hypermethylation and nuclear envelope invaginations in the absence of ATM. Furthermore, laser-capture proteomics of Purkinje cells from A-T patients revealed dysregulated mechanotransduction and chromatin remodeling pathways. Finally, we present in vitro evidence that promoting chromatin relaxation through various inhibitor treatments can rescue the nuclear shape defects in A-T Purkinje cells. Our findings suggest that mechanical stress in A-T Purkinje cells may contribute to their degeneration in Ataxia telangiectasia and highlight innovative therapeutic strategies targeting nuclear mechano-dysfunction in A-T patients
ZC3H14, a new player in the early response to DNA double strand breaks
No full textThe primary goal of all organisms is to pass down intact genetic information to the next generation, despite mutagenic threats from both endogenous and exogenous sources. To prevent accumulation of DNA damage, cells have developed complex mechanisms that detect and respond to different forms of lesions. These complex pathways are collectively called the DNA damage response (DDR). Impaired responses to DNA damage drive oncogenesis, neurodegeneration, and immunodeficiencies. Both DNA damaging agents and drugs which target specific repair proteins are a mainstay of modern current therapeutic approaches. Thus, to understand the aetiology of disease, the impact of current therapeutic interventions, and to develop further precision medicines, it is vital to understand the complex series of pathways involved in the DDR. One of the major protein kinases involved in signal transduction within the cells’ response to double strand breaks (DSBs) is Ataxia-telangiectasia mutated (ATM). Previous research from Prof. Noel Lowndes’ laboratory identified a zinc-finger protein, ZC3H14, as a DNA damage-dependent ATM-interacting partner. This is an unexpected interaction as ZC3H14’s canonical roles are in mRNA processing, including regulation of poly(A) tail length and mRNA nuclear export. Similarly to ATM and other DDR proteins, ZC3H14 has both neurological and links to cancer when it its function is impaired. This novel data implicates ZC3H14 in the DDR, as well as placing it in a disease-critical pathway. Unpublished data has placed ZC3H14 in the ‘Early’ response to DSBs, which occurs minutes after break formation. Cells lacking ZC3H14 showed striking repair defects: cells become sensitive to ionising radiation (IR); depletion of ZC3H14 results in a persistent increase in the damage markers γH2AX foci and ATM-pS1981; and knockdown of ZC3H14 ablated irradiation-induced foci (IRIF) of ‘Early’ DNA damage response proteins downstream of MDC1. In addition, ZC3H14 co-immunoprecipitated with both ATM and MDC1. Preliminary data suggests that ZC3H14 is more involved in NHEJ than HR, despite its placement in the response upstream of pathway choice. Here, we aim to deepen our understanding of the role of ZC3H14 in the DDR using bioinformatic, cellular and molecular geology, and biochemical methodology. We generated ZC3H14KO cells, allowing us to study the placement of ZC3H14 in the DDR pathway, and to confirm the defect of DDR protein recruitment via independent methods.
These cells show an increase in endogenous damage and impaired foci formation. We designed GFP-ZC3H14 domain mutants that truncate the N-terminal PWI-like domain or the five tandem C-terminal zinc finger domains in order to explore the mechanisms of these domains on ZC3H14’s role in repair. We were able to determine that ZC3H14 is a damage-specific substrate of ATM, and that it localises in proximity to damage-activated ATM-pS1981 in vivo. Despite these interactions, we were unable to visualise ZC3H14 at damage foci, and hypothesise that due to ZC3H14’s heavy localisation to nuclear speckles, there may be only a subset of ZC3H14 at the speckle’s periphery that is phosphorylated and responsive to damage. As well, ZC3H14 has a large intrinsically disordered domain which could contribute to its localisation. Interestingly, we used the newly released AlphaFold3 server to predict that ZC3H14 could contain a disorder-toorder region which has an alpha-helixes rich folded structure in the presence of DNA and other DDR proteins, but not nuclear speckle proteins. All of this points to a damageactivated phosphorylated form of ZC3H14 which has some as-yet unsolved role at DSBs. This role is likely in regulating the recruitment of MDC1 or RNF8, but could also have to do with phase separation of IRIF condensates, or provide a link between mRNA processing and DNA repair. The project aims to characterize a novel role for a zinc-finger protein, ZC3H14, in the DNA damage response (DDR): its interactions with Ataxia-telangiectasia mutated (ATM), its effect on cell survival, its impact on formation of irradiation-induced foci (IRIF), its mechanism of action, and its signature in human diseases. ZC3H14 has not been previously implicated in DNA repair. Many proteins within this pathway can be targeted for synthetic lethality, to be taken advantage of both for molecular tools for further study, and for druggable targets with the advent of personalised medicines.Hardiman Research Fun
Social frailty and social isolation in the context of dementia: A simultaneous concept analysis
No full textObjectives
Early management of risk factors related to social health such as social frailty and social isolation could modify the progression of dementia and reduce its impact on people with dementia. However, due to overlapping definitions and interchangeable use of measurement tools, the precise distinction between these two concepts is unclear. This simultaneous concept analysis aimed to examine the definitions and interrelationships between the concepts of social frailty and social isolation within the context of dementia.
Methods
The simultaneous concept analysis method developed by Haase et al. was employed. A literature search was conducted across six databases (Ovid Medline, CINAHL, PsycINFO, Scopus, Embase and Cochrane Library) to retrieve original research, review and theoretical papers, published in English. Data from the literature was synthesised and analysed thematically following Braun and Clarke's six steps.
Results
The attributes of concepts of social frailty and social isolation overlap, including being alone and having limited or less social activities, engagements or interactions. The specific attributes of social frailty are financial difficulties and less talk while social isolation is distinctly marked by a lack of social networks or social relationships. Socio-economic welfare is a specific antecedent of social frailty, while decreased access to social resources and lower social well-being are distinctive consequences of social isolation. Cognitive decline and dementia are distinctive antecedents of social isolation; however, they also exist as shared consequences of both social frailty and social isolation.
Conclusions
This simultaneous concept analysis clarified the similarities and differences between social frailty and social isolation in the context of dementia. A clearer understanding of the interrelationships between social frailty and social isolation and distinct and overlapping characteristics of them will support strategies to comprehensively address social health issues experienced by people with dementia.This research was funded by University of Galway - Chinese Scholarship Council Research Scholarship, grant number 202308300025.peer-reviewe
Bias tuning of an event camera for in-cabin automotive environments
No full textThis research proposes solutions to the challenges of integrating event cameras into real world applications, with a specific focus on in-cabin driver monitoring systems (DMS). While the world’s first event-based DMS demonstrated the ability to track a driver’s face, count blinks, and estimate head pose and gaze under controlled office lighting, it’s performance was degraded under real-world driving conditions. Factors such as varying lighting environments (e.g., day, night, flickering, and unevenly lit roads) and interference from in-cabin screens or
sensors adversely affected performance. To address these challenges, first, we propose novel mathematical metrics, and utilize others including average gradient (AG) and YOLO confidence scores to quantitatively assess DMS performance. Second, a performance monitoring framework was proposed, leveraging these metrics to guide system optimization. Third, a convolutional neural network (CNN) was employed to detect and mitigate specific lighting issue, flickering. Finally, a fully blind optimization approach, using Nelder-Mead algorithm, was implemented to dynamically tune event camera biases (e.g., bias_fo, bias_diff_on, bias_diff_off, bias_refr, and bias_hpf). This approach ensures robust system performance and optimized control of event output without requiring additional filters, thereby minimizing design complexity. The proposed methods significantly enhance event camera performance, improving reliability in challenging scenarios such as low-light environments, high-frequency flickering, and other dynamic conditions. While the focus of this work is primarily on DMS, the findings lay the groundwork for broader applications of event cameras in fields such as robotics, augmented reality, and smart cities. Future work will explore AI-driven adaptive optimization strategies and domain-specific metrics to further enhance the potential of event cameras in next-generation technologies. By bridging the gap between sensor technology and real-world requirements, this research demonstrates that event cameras can transform driver monitoring systems and open up opportunities for advancements in automotive safety, automation, and precision vision systems