Conjugation at the oligonucleotide level based on isoxazole phosphoramidites generated by click chemistry

The versatility of the isoxazole generating nitrile oxide–alkyne Huisgen cycloaddition for provision of chemically modified oligonucleotides has been extended; in a novel approach isoxazole conjugated oligodeoxyribonucleotides have been constructed by phosphoramidite chemistry of isoxazole derivatives previously generated by nitrile oxide–alkyne click chemistry. The conjugation involves manual solid phase synthesis at room temperature in aqueous ethanol and proceeds in high yield

An Idirchultúrthacht Iarchoilíneach i nGearrscéalaíocht Phádraic Bhreathnaigh.

Scríbhneoir é Pádraic Breathnach a bhfuil blianta fada caite aige i mbun gearrscéalaíochta. Go dtí seo ní dhearnadh plé cuimsitheach ar a shaothar gearrscéalaíochta ina iomláine. Is éard is cuspóir don tráchtas seo ná léamh faoi leith amháin a sholáthar ar an ngearrscéalaíocht sin chun léargas a thabhairt ar lárnacht na hidirchultúrthachta iarchoilíní inti. Chuige sin, déanfar iniúchadh ar chomhthéacs na hidirchultúrthachta iarchoilíní, agus ar an áit faoi leith atá ag Éirinn sa díospóireacht ar an gcoilíneachas agus ar an iarchoilíneachas. Áiteofar go bhfuil áit lárnach ag Éirinn agus ag litríocht na hÉireann, go háirithe ag litríocht na Gaeilge, sa phlé sin. Féachfar le haitheantas cuí a thabhairt do ghearrscéalaíocht an Bhreathnaigh sa dioscúrsa sin. Tabharfar faoi léargas a sholáthar ar chastacht cheist na hidirchultúrthachta a eascraíonn as próiseas an choilíneachais agus ar thábhacht na teanga dúchasaí i bpróiseas an díchoilínithe. Déanfar iniúchadh ar chastacht cheist na hidirchúltúrthachta a eascraíonn as an eispéireas coilíneach i litríocht na Gaeilge, á léiriú trí mhionphlé ar ghearrscéalaíocht Phádraic Bhreathnaigh. Féachfar ar fhéinaitheantas agus ar speictream an déachais idirchultúrtha i gcarachtracht scéalta an Bhreathnaigh, agus ar ghnéithe d’fhéinaitheantas an scríbhneora féin. Scríbhneoir Breac-Ghaeltachta is ea Pádraic Breathnach agus tá an tionchar sin soiléir ina shaothar cruthaitheach. Déanfar plé ar thionchar na timpeallachta ar a shaothar de réir theoiric an Third Space, a d’fhorbair Homi Bhabha. Speictream is ea an déachas idirchultúrtha a réimníonn an aonchultúrthacht, an chrossíolracht, agus an cumasc cultúrtha. Pléifear gearrscéalaíocht Phádraic Bhreathnaigh i gcomhthéacs an speictrim sin. Ina theannta sin, déanfar tábhacht Phádraic Bhreathnaigh mar scríbhneoir idirchultúrtha a chomhthéacsú i gcúlra socheacnamaíoch Éire a linne agus i gcúlra liteartha a linne féin. Mar thoradh ar léamh na hidirchultúrthachta iarchoilíní a dhéanfar sa tráchtas seo ar ghearrscéalaíocht Phádraic Bhreathnaigh, tá léamh nua ar shaothar an scríbhneora seo á chur ar fáil atá inchomparáide le saothar scríbhneoirí iarchoilíneacha eile ar fud na cruinne. Ag eascairt as an taighde seo, is léir gur réimse critice an idirchultúrthacht iarchoilíneach arbh fhiú é a fhorbairt a thuilleadh amach anseo mar uirlis chritice do litríocht Ghaeilge na linne seo, agus saothair liteartha scríbhneoirí eile na Gaeilge á meas

Isoxazole linked oligonucleotide conjugates by on resin and previously clicked nitrile oxide alkyne cycloadditions

Bioconjugation protocols in environments free from residual copper or other catalytic components are important for therapeutic and biomedical applications as well as in living systems. In this communication we discuss the versatility of the catalyst free, isoxazole generating nitrile oxide alkyne Huisgen cycloaddition for provision of chemically modified oligonucleotide conjugates. Two distinct approaches will be demonstrated. In the first we discuss on resin cylcoaddition between in situ generated nitrile oxide

Slán Beo le Saol an Bhlascaoid: Tionchar na hlmirce ar an Oileán Tiar agus an Tréigean Deireanach

Is éard is aidhm don tráchtas seo ná iniúchadh a dhéanamh ar théama na himirce i litríocht an Bhlascaoid Mhóir. Breathnófar ar shaothair dhírbheathaisnéise, saothair chin lae agus ailt mhuintir an Bhlascaoid agus, chomh maith leis sin, ar agallaimh a cuireadh ar Bhlascaodaigh faoi leith, agus ar dhaoine a bhain leis an mBlascaod Mór, chun spléachadh a fháil ar thuiscintí agus ar thuairimí phobal an Bhlascaoid i leith na himirce. Bainfear leas as béaloideas agus dinnsheanchas na mBlascaodaí, ar uairibh, tríd an tráchtas seo, chun tuiscint a fháil ar nósanna agus ar luachanna mhuintir an Bhlascaoid. Beifear ag breathnú ar an tslí inar scríobh muintir an Bhlascaoid, mar aon le daoine a chuaigh isteach ar an mBlascaod, faoi eispéireas na himirce, agus faoina tionchar ar an bpobal beag a mhair ar an Oileán iargúlta sin siar ó chósta Chiarraí. Déanfar iniúchadh ar thuairimí na mBlascaodach i leith na himirce, agus cuirfear peirspeictíochtaí éagsúla na ndaoine os comhair an léitheora, ón seanóir nár fhág an tOileán Tiar riamh le dui go ‘Tir an Allais’, go dti an páiste a bhreathnaiodh ar na fir is na mná óga a théadh sali gach bliain, ag tnûth leis an mbliain a mbeadh sé féin in aois imeachta; ón mbean ôg neamhspléach a bhreathnaiodh ar an imirce mar shli éalaithe ón gcruachás ina raibh si ar an ‘árthach bàite’, agus a chuaigh sali go ‘Tir na mBrionglóidí’ chun saol iontach nua-aimseartha a chaitheamh ami beag beann ar chumhacht mhithrocaireach na farraige, go dti an t-ógánach uaigneach a d’fhan ar a oileán dúchais, nach raibh uaidh riamh ach saol an Oileáin Tiar ach a bhraith a chairde uaidh agus iad bailithe leo sali go Meiriceâ

Mathematics Anxiety and Metacognitive Processes: Proposal for a New Line of Inquiry

This paper presents a proposal for a new area of investigation that connects the metacognition literature, and especially the recently developed meta-reasoning framework, with research into mathematical reasoning, mathematics learning, and mathematics anxiety. Whereas the literature on mathematics anxiety focusses on the end result of learning and problem-solving, the metacognitive approach can offer further insight by a fine-grained analysis of the stages of these processes. In particular, it provides tools for exposing students' initial assessment of tasks and test situations, the targets they set for themselves, the process of monitoring progress, and decisions to stick with or abandon a particular solution. The paper outlines various ways in which the metacognitive approach could be used to investigate the effects of mathematics anxiety on mathematics learning and problem solving. This approach could help in answering questions like: Do anxious and non-anxious learners differ in how they prepare for an exam? Are anxious students more or less prone to overconfidence than non-anxious students? What metacognitive decisions mediate maths anxious participants' tendency to give up on problems too early? Additionally, this line of work has the potential to significantly expand the scope of metacognitive investigations and provide novel insights into individual differences in the metacognitive regulation of learning and problem solving. It could also offer some practical benefits by focusing the attention of educational designers on particular components within the learning process of anxious students.<br /

A Common Variant in the Adaptor Mal Regulates Interferon Gamma Signaling

Humans that are heterozygous for the common S180L polymorphism in the Toll-like receptor (TLR) adaptor Mal (encoded by TIRAP) are protected from a number of infectious diseases, including tuberculosis (TB), whereas those homozygous for the allele are at increased risk. The reason for this difference in susceptibility is not clear. We report that Mal has a TLR-independent role in interferon-gamma (IFN-gamma) receptor signaling. Mal-dependent IFN-gamma receptor (IFNGR) signaling led to mitogen-activated protein kinase (MAPK) p38 phosphorylation and autophagy. IFN-gamma signaling via Mal was required for phagosome maturation and killing of intracellular Mycobacterium tuberculosis (Mtb). The S180L polymorphism, and its murine equivalent S200L, reduced the affinity of Mal for the IFNGR, thereby compromising IFNGR signaling in macrophages and impairing responses to TB. Our findings highlight a role for Mal outside the TLR system and imply that genetic variation in TIRAP may be linked to other IFN-gamma-related diseases including autoimmunity and cancer

How does socio-economic position (SEP) get biologically embedded? A comparison of allostatic load and the epigenetic clock(s)

Individuals of lower socio-economic position (SEP) carry a heavier burden of disease and morbidity and live shorter lives on average compared with their more advantaged counterparts. This has sparked research interest in the processes and mechanisms via which social adversity gets biologically embedded. The present study directly compares the empirical worth of two candidate mechanisms: Allostatic Load (AL) and the Epigenetic Clock(s) for advancing our understanding of embodiment using a sub-sample of 490 individuals from the Irish Longitudinal Study (TILDA) who were explicitly selected for this purpose based on their inter-generational life course social class trajectory. A battery of 14 biomarkers representing the activity of 4 different physiological systems: Immunological, Cardiovascular, Metabolic, and Renal was used to construct the AL score. Biomarkers were dichotomised into high and low risk groups according to sex-specific quartiles of risk and summed to create a count ranging from 0-14. Three measures of epigenetic age acceleration were computed according to three sets of age-associated Cytosine-phosphate-Guanine (CpG) sites described by Horvath, Hannum and Levine. AL was strongly socially patterned across a number of measures of SEP, while the epigenetic clocks were not. AL partially mediated the association between measures of SEP and an objective measure of physiological functioning: performance on the Timed Up and Go (TUG test). We conclude that AL may represent the more promising candidate for understanding the pervasive link between SEP and health.Peer reviewe

Contexts and mechanisms that promote access to healthcare for populations experiencing homelessness: A realist review

ObjectiveThe objective of this study was to identify and understand the health system contexts and mechanisms that allow for homeless populations to access appropriate healthcare when needed.DesignA realist review.Data sourcesOvid MEDLINE, embase.com, CINAHL, ASSIA and grey literature until April 2019.Eligibility criteria for selecting studiesThe purpose of the review was to identify health system patterns which enable access to healthcare for people who experience homelessness. Peer-reviewed articles were identified through a systematic search, grey literature search, citation tracking and expert recommendations. Studies meeting the inclusion criteria were assessed for rigour and relevance and coded to identify data relating to contexts, mechanisms and/or outcomes.AnalysisInductive and deductive coding was used to generate context–mechanism–outcome configurations, which were refined and then used to build several iterations of the overarching programme theory.ResultsSystematic searching identified 330 review articles, of which 24 were included. An additional 11 grey literature and primary sources were identified through citation tracking and expert recommendation. Additional purposive searching of grey literature yielded 50 records, of which 12 were included, for a total of 47 included sources. The analysis found that healthcare access for populations experiencing homelessness is improved when services are coordinated and delivered in a way that is organised around the person with a high degree of flexibility and a culture that rejects stigma, generating trusting relationships between patients and staff/practitioners. Health systems should provide long-term, dependable funding for services to ensure sustainability and staff retention.ConclusionsWith homelessness on the rise internationally, healthcare systems should focus on high-level factors such as funding stability, building inclusive cultures and setting goals which encourage and support staff to provide flexible, timely and connected services to improve access.</jats:sec