The National University of Ireland Maynooth , known as Maynooth University since August 2014, is a university in the town of Maynooth, Ireland. It was founded by the Universities Act, 1997 as a constituent university of the National University of Ireland, but it may be considered Ireland's second oldest university, having been formed from St Patrick's College, Maynooth which was founded in 1795. Wikipedia.
Humphries F.,National University of Ireland, Maynooth
Cell Death and Differentiation | Year: 2014
Innate immunity represents the first line of defence against invading pathogens. It consists of an initial inflammatory response that recruits white blood cells to the site of infection in an effort to destroy and eliminate the pathogen. Some pathogens replicate within host cells, and cell death by apoptosis is an important effector mechanism to remove the replication niche for such microbes. However, some microbes have evolved evasive strategies to block apoptosis, and in these cases host cells may employ further countermeasures, including an inflammatory form of cell death know as necroptosis. This review aims to highlight the importance of the RIP kinase family in controlling these various defence strategies. RIP1 is initially discussed as a key component of death receptor signalling and in the context of dictating whether a cell triggers a pathway of pro-inflammatory gene expression or cell death by apoptosis. The molecular and functional interplay of RIP1 and RIP3 is described, especially with respect to mediating necroptosis and as key mediators of inflammation. The function of RIP2, with particular emphasis on its role in NOD signalling, is also explored. Special attention is given to emphasizing the physiological and pathophysiological contexts for these various functions of RIP kinases.Cell Death and Differentiation advance online publication, 22 August 2014; doi:10.1038/cdd.2014.126.
Heaney F.,National University of Ireland, Maynooth
European Journal of Organic Chemistry | Year: 2012
The need for precise and flexible synthetic methodology to underpin modern research in chemical biology and materials science has fuelled a resurgence of interest in Huisgen 1,3-dipolar cycloaddition chemistry. Of late, the in vogue chemistry for the assembly of complex biological molecules and specialist materials has been the copper-catalysed azide alkyne cycloaddition (CuAAC) reaction. However, in certain circumstances aversion to the copper catalyst flaws this approach and alternatives have been sought. Click chemistry has developed beyond the original triazole-forming trick and azides are no longer the only dipoles pursued as click cycloaddition partners. This article reviews some of the complications of the CuAAC reaction and evaluates the potential of nitrile oxide/alkyne cycloaddition (NOAC) as a covalent conjugation tool. With a focus on applications in nucleic acid chemistry and materials science it presents the case for a prominent position for nitrile oxides in the catalyst-free bioconjugation toolbox. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
English K.,National University of Ireland, Maynooth
Immunology and Cell Biology | Year: 2013
Multipotent mesenchymal stromal cells (MSCs) have generated considerable interest in the fields of regenerative medicine, cell therapy and immune modulation. Over the past 5 years, the initial observations that MSCs could enhance regeneration and modulate immune responses have been significantly advanced and we now have a clearer picture of the effects that MSCs have on the immune system particularly in the context of inflammatory-mediated disorders. A number of mechanisms of action have been reported in MSC immunomodulation, which encompass the secretion of soluble factors, induction of anergy, apoptosis, regulatory T cells and tolerogenic dendritic cells. It is clear that MSCs modulate both innate and adaptive responses and evidence is now emerging that the local microenvironment is key in the activation or licensing of MSCs to become immunosuppressive. More recently, studies have suggested that MSCs have the capacity to sense their environment and have a role in pathogen clearance in conjunction with the resolution of insult or injury. This review focuses on the mechanisms of MSC immunomodulation discussing the multistep process of MSC localisation at sites of inflammation, the cross talk between MSCs and the local microenvironment as well as the subsequent mechanisms of action used to resolve inflammation. © 2013 Australasian Society for Immunology Inc. All rights reserved.
Doyle S.,National University of Ireland, Maynooth
BMC genomics | Year: 2014
BACKGROUND: Aspergillus fumigatus produces a number of secondary metabolites, one of which, gliotoxin, has been shown to exhibit anti-fungal activity. Thus, A. fumigatus must be able to protect itself against gliotoxin. Indeed one of the genes in the gliotoxin biosynthetic gene cluster in A. fumigatus, gliT, is required for self-protection against the toxin- however the global self-protection mechanism deployed is unclear. RNA-seq was employed to identify genes differentially regulated upon exposure to gliotoxin in A. fumigatus wild-type and A. fumigatus ∆gliT, a strain that is hypersensitive to gliotoxin.RESULTS: Deletion of A. fumigatus gliT resulted in altered expression of 208 genes (log2 fold change of 1.5) when compared to A. fumigatus wild-type, of which 175 genes were up-regulated and 33 genes were down-regulated. Expression of 164 genes was differentially regulated (log2 fold change of 1.5) in A. fumigatus wild-type when exposed to gliotoxin, consisting of 101 genes with up-regulated expression and 63 genes with down-regulated expression. Interestingly, a much larger number of genes, 1700, were found to be differentially regulated (log2 fold change of 1.5) in A. fumigatus ∆gliT when challenged with gliotoxin. These consisted of 508 genes with up-regulated expression, and 1192 genes with down-regulated expression. Functional Catalogue (FunCat) classification of differentially regulated genes revealed an enrichment of genes involved in both primary metabolic functions and secondary metabolism. Specifically, genes involved in gliotoxin biosynthesis, helvolic acid biosynthesis, siderophore-iron transport genes and also nitrogen metabolism genes and ribosome biogenesis genes underwent altered expression. It was confirmed that gliotoxin biosynthesis is induced upon exposure to exogenous gliotoxin, production of unrelated secondary metabolites is attenuated in A. fumigatus ∆gliT, while quantitative proteomic analysis confirmed disrupted translation in A. fumigatus ∆gliT challenged with exogenous gliotoxin.CONCLUSIONS: This study presents the first global investigation of the transcriptional response to exogenous gliotoxin in A. fumigatus wild-type and the hyper-sensitive strain, ∆gliT. Our data highlight the global and extensive affects of exogenous gliotoxin on a sensitive strain devoid of a self-protection mechanism and infer that GliT functionality is required for the optimal biosynthesis of selected secondary metabolites in A. fumigatus.
Ohlendieck K.,National University of Ireland, Maynooth
Biomarkers in Medicine | Year: 2013
Disease-specific biomarkers play a central diagnostic and therapeutic role in muscle pathology. Serum levels of a variety of muscle-derived enzymes are routinely used for the detection of muscle damage in diagnostic procedures, as well as for the monitoring of physical training status in sports medicine. Over the last few years, the systematic application of mass spectrometry-based proteomics for studying skeletal muscle degeneration has greatly expanded the range of muscle biomarkers, including new fiber-associated proteins involved in muscle transformation, muscular atrophy, muscular dystrophy, motor neuron disease, inclusion body myositis, myotonia, hypoxia, diabetes, obesity and sarcopenia of old age. These mass spectrometric studies have clearly established skeletal muscle proteomics as a reliable method for the identification of novel indicators of neuromuscular diseases. © 2013 Future Medicine Ltd.