Institutional Mergers in Ireland

The importance of knowledge as a driver of social and economic growth and prosperity, and the increasingly competitive “global race for knowledge and talent” (Hazelkorn, Higher Educ Manage Policy 21(1):55–76, 2009) have combined to transform the higher education landscape, forcing national governments and higher education institutions (HEIs) to pursue new ways of addressing the challenges of a multi-polar world order. Rising demand for higher education (HE), as part of the broader shift from elite to mass to universal participation, has led to the emergence of new models of provision. At the same time, many governments face restrictions on public resources due to high levels of public and private debt; accordingly, system-level and institutional restructuring has been contemplated as a way to enhance quality, performance and efficiency

Imaging in the time of NFD/NSF: do we have to change our routines concerning renal insufficiency?

To date there are potential chronology-based but not conclusive reasons to believe that at least some of the gadolinium complexes play a causative role in the pathophysiology of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). Still, the exact pathogenesis and the risk for patients is unclear beside the obvious connection to moderate to severe renal insufficiency. So far, MR imaging with Gd-enhancement was regarded as the safest imaging modality in these patients—the recent development creates tremendous uncertainty in the MR-community. Nevertheless, one should remember that, despite the over 200 cases of NSF and about 100 with proven involvement of Gd3+, the vast majority of over 200 million patients exposed to gadolinium since the 1980s have tolerated these agents well. Importantly, NSF is a rare disease and does not appear to occur in patients without renal impairment. Many patients and researchers have undergone MR investigations with Gd exposure in the past. For those, it is essential to know about the safety of the agents at normal renal function. We can hope that pharmacoepidemiological and preclinical studies will allow us to better understand the pathophysiology and role of the various MR contrast agents in the near future

High sample throughput genotyping for estimating C-lineage introgression in the dark honeybee: an accurate and cost-effective SNP-based tool

The natural distribution of the honeybee (Apis mellifera L.) has been changed by humans in recent decades to such an extent that the formerly widest-spread European subspecies, Apis mellifera mellifera, is threatened by extinction through introgression from highly divergent commercial strains in large tracts of its range. Conservation efforts for A. m. mellifera are underway in multiple European countries requiring reliable and cost-efficient molecular tools to identify purebred colonies. Here, we developed four ancestry-informative SNP assays for high sample throughput genotyping using the iPLEX Mass Array system. Our customized assays were tested on DNA from individual and pooled, haploid and diploid honeybee samples extracted from different tissues using a diverse range of protocols. The assays had a high genotyping success rate and yielded accurate genotypes. Performance assessed against whole-genome data showed that individual assays behaved well, although the most accurate introgression estimates were obtained for the four assays combined (117 SNPs). The best compromise between accuracy and genotyping costs was achieved when combining two assays (62 SNPs). We provide a ready-to-use cost-effective tool for accurate molecular identification and estimation oinfo:eu-repo/semantics/publishedVersio

JAK2 V617F Constitutive Activation Requires JH2 Residue F595: A Pseudokinase Domain Target for Specific Inhibitors

The JAK2 V617F mutation present in over 95% of Polycythemia Vera patients and in 50% of Essential Thrombocythemia and Primary Myelofibrosis patients renders the kinase constitutively active. In the absence of a three-dimensional structure for the full-length protein, the mechanism of activation of JAK2 V617F has remained elusive. In this study, we used functional mutagenesis to investigate the involvement of the JH2 αC helix in the constitutive activation of JAK2 V617F. We show that residue F595, located in the middle of the αC helix of JH2, is indispensable for the constitutive activity of JAK2 V617F. Mutation of F595 to Ala, Lys, Val or Ile significantly decreases the constitutive activity of JAK2 V617F, but F595W and F595Y are able to restore it, implying an aromaticity requirement at position 595. Substitution of F595 to Ala was also able to decrease the constitutive activity of two other JAK2 mutants, T875N and R683G, as well as JAK2 K539L, albeit to a lower extent. In contrast, the F595 mutants are activated by erythropoietin-bound EpoR. We also explored the relationship between the dimeric conformation of EpoR and several JAK2 mutants. Since residue F595 is crucial to the constitutive activation of JAK2 V617F but not to initiation of JAK2 activation by cytokines, we suggest that small molecules that target the region around this residue might specifically block oncogenic JAK2 and spare JAK2 wild-type

Before and after study of bar workers' perceptions of the impact of smoke-free workplace legislation in the Republic of Ireland

<p>Abstract</p> <p>Background</p> <p><it>Objectives</it>: To compare support for, and perceptions of, the impacts of smoke-free workplace legislation among bar workers in the Republic of Ireland (ROI) pre- and post-implementation, and to identify predictors of support for the legislation.</p> <p>Methods</p> <p><it>Setting</it>: Public houses (pubs) in three areas of the ROI.</p> <p><it>Design</it>: Comparisons pre- and post-implementation of smoke-free workplace legislation.</p> <p><it>Participants</it>: From a largely non-random selection, 288 bar workers volunteered for the baseline survey; 220 were followed up one year later (76.4%).</p> <p><it>Outcome measures: </it>Level of support for the legislation, attitude statements concerning potential impacts of the law and modelled predictors of support for the legislation.</p> <p>Results</p> <p>Pre-implementation 59.5% of participants supported the legislation, increasing to 76.8% post-implementation. Support increased among smokers by 27.3 percentage points from 39.4% to 66.7% (p < 0.001) and among non-smokers by 12.4% percentage points from 68.8% to 81.2% (p = 0.003).</p> <p>Pre-legislation three-quarters of participants agreed that the legislation would make bars more comfortable and was needed to protect workers' health. Post-legislation these proportions increased to over 90% (p < 0.001). However, negative perceptions also increased, particularly for perceptions that the legislation has a negative impact on business (from 50.9% to 62.7%, p = 0.008) and that fewer people would visit pubs (41.8% to 62.7%, p < 0.001). After adjusting for relevant covariates, including responses to the attitude statements, support for the ban increased two to three-fold post-implementation. Regardless of their views on the economic impact, most participants agreed, both pre- and post-implementation, that the legislation was needed to protect bar workers' health.</p> <p>Conclusion</p> <p>Smoke-free legislation had the support of three-quarters of a large sample of bar workers in the ROI. However, this group holds complex sets of both positive and negative perspectives on the legislation. Of particular importance is that negative economic perceptions did not diminish the widely held perception that the ban is needed to protect workers' health.</p

Proteomic Candidate Biomarkers of Drug-Induced Nephrotoxicity in the Rat

Improved biomarkers of acute nephrotoxicity are coveted by the drug development industry, regulatory agencies, and clinicians. In an effort to identify such biomarkers, urinary peptide profiles of rats treated with two different nephrotoxins were investigated. 493 marker candidates were defined that showed a significant response to cis-platin comparing a cis-platin treated cohort to controls. Next, urine samples from rats that received three consecutive daily doses of 150 or 300 mg/kg gentamicin were examined. 557 potential biomarkers were initially identified; 108 of these gentamicin-response markers showed a clear temporal response to treatment. 39 of the cisplatin-response markers also displayed a clear response to gentamicin. Of the combined 147 peptides, 101 were similarly regulated by gentamicin or cis-platin and 54 could be identified by tandem mass spectrometry. Most were collagen type I and type III fragments up-regulated in response to gentamicin treatment. Based on these peptides, classification models were generated and validated in a longitudinal study. In agreement with histopathology, the observed changes in classification scores were transient, initiated after the first dose, and generally persistent over a period of 10–20 days before returning to control levels. The data support the hypothesis that gentamicin-induced renal toxicity up-regulates protease activity, resulting in an increase in several specific urinary collagen fragments. Urinary proteomic biomarkers identified here, especially those common to both nephrotoxins, may serve as a valuable tool to investigate potential new drug candidates for the risk of nephrotoxicity

The Development of Inclusive Learning Relationships in Mainstream Settings: A Multimodal Perspective

The debate regarding the inclusion of children with Special Educational Needs and Disabilities (SEND) in mainstream education in the UK partly revolves around what makes the classroom environment inclusive. Through the potential offered by the specific qualitative methodologies employed, this study aimed to explore the development of teachers’ pedagogical practices and learning relationships upon the inclusive education of children with special educational needs and disabilities in two primary school classes. The study considered the views and behaviours of primary school pupils with and without special educational needs, primary school teachers and teaching assistants (TAs) in one mainstream school. Drawing on a multimodal approach to discourse analysis to account for the complex relationships between symbolic and non-verbal modes of classroom signification, the study explored how meaning is produced in classrooms and children’s modes of communication, as well as in teachers’ practices. The two classes are compared on the basis of teaching observations, interviews, transcripts of dialogues, and analyses of classroom organisation and decoration. This paper suggests that the greatest influence on the educational and social outcomes of students with special educational needs is the behaviour and practices of the classroom teacher

Sensitive Detection of p65 Homodimers Using Red-Shifted and Fluorescent Protein-Based FRET Couples

BACKGROUND: Fluorescence Resonance Energy Transfer (FRET) between the green fluorescent protein (GFP) variants CFP and YFP is widely used for the detection of protein-protein interactions. Nowadays, several monomeric red-shifted fluorescent proteins are available that potentially improve the efficiency of FRET. METHODOLOGY/PRINCIPAL FINDINGS: To allow side-by-side comparison of several fluorescent protein combinations for detection of FRET, yellow or orange fluorescent proteins were directly fused to red fluorescent proteins. FRET from yellow fluorescent proteins to red fluorescent proteins was detected by both FLIM and donor dequenching upon acceptor photobleaching, showing that mCherry and mStrawberry were more efficient acceptors than mRFP1. Circular permutated yellow fluorescent protein variants revealed that in the tandem constructs the orientation of the transition dipole moment influences the FRET efficiency. In addition, it was demonstrated that the orange fluorescent proteins mKO and mOrange are both suitable as donor for FRET studies. The most favorable orange-red FRET pair was mKO-mCherry, which was used to detect homodimerization of the NF-kappaB subunit p65 in single living cells, with a threefold higher lifetime contrast and a twofold higher FRET efficiency than for CFP-YFP. CONCLUSIONS/SIGNIFICANCE: The observed high FRET efficiency of red-shifted couples is in accordance with increased Förster radii of up to 64 A, being significantly higher than the Förster radius of the commonly used CFP-YFP pair. Thus, red-shifted FRET pairs are preferable for detecting protein-protein interactions by donor-based FRET methods in single living cells

Whole genome SNP-associated signatures of local adaptation in honeybees of the Iberian Peninsula

The availability of powerful high-throughput genomic tools, combined with genome scans, has helped identifying genes and genetic changes responsible for environmental adaptation in many organisms, including the honeybee. Here, we resequenced 87 whole genomes of the honeybee native to Iberia and used conceptually different selection methods (Samβada, LFMM, PCAdapt, iHs) together with in sillico protein modelling to search for selection footprints along environmental gradients. We found 670 outlier SNPs, most of which associated with precipitation, longitude and latitude. Over 88.7% SNPs laid outside exons and there was a significant enrichment in regions adjacent to exons and UTRs. Enrichment was also detected in exonic regions. Furthermore, in silico protein modelling suggests that several non-synonymous SNPs are likely direct targets of selection, as they lead to amino acid replacements in functionally important sites of proteins. We identified genomic signatures of local adaptation in 140 genes, many of which are putatively implicated in fitness-related functions such as reproduction, immunity, olfaction, lipid biosynthesis and circadian clock. Our genome scan suggests that local adaptation in the Iberian honeybee involves variations in regions that might alter patterns of gene expression and in protein-coding genes, which are promising candidates to underpin adaptive change in the honeybee.John C. Patton, Phillip San Miguel, Paul Parker, Rick Westerman, University of Purdue, resequenced the 87 whole genomes of IHBs. Jose Rufino provided computational resources at IPB. Analyses were performed using the computational resources at the Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX), Uppsala University. DH was supported by a PhD scholarship (SFRH/BD/84195/2012) from the Portuguese Science Foundation (FCT). MAP is a member of and receives support from the COST Action FA1307 (SUPER-B). This work was supported by FCT through the programs COMPETE/QREN/EU (PTDC/BIA-BEC/099640/2008) and the 2013-2014 BiodivERsA/FACCE-JPI (joint call for research proposals, with the national funders FCT, Portugal, CNRS, France, and MEC, Spain) to MAP