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Displaying Results 226 - 250 of 2128 on page 10 of 86
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Identification of the Synthetic Cannabinoid R()WIN55,212-2 as a Novel Regulator of IFN Regulatory Factor 3 Activation and IFN- Expression
(2011)
Downer, Eric J.; Clifford, Eileen; Gran, Bruno; Hendrik, J. Nel; Fallon, Padraig G.; Mo...
Identification of the Synthetic Cannabinoid R()WIN55,212-2 as a Novel Regulator of IFN Regulatory Factor 3 Activation and IFN- Expression
(2011)
Downer, Eric J.; Clifford, Eileen; Gran, Bruno; Hendrik, J. Nel; Fallon, Padraig G.; Moynagh, Paul N.
Abstract:
Beta Interferons (IFN-βs) represent one of the first line treatments for relapsing remitting multiple sclerosis (RRMS), slowing disease progression whilst reducing the frequency of relapses. Despite this, more effective, well tolerated therapeutic strategies are needed. Cannabinoids palliate experimental autoimmune encephalomyelitis (EAE) symptoms and have therapeutic potential in MS patients although the precise molecular mechanism for these effects is not understood. Toll-like receptor (TLR) signaling controls innate immune responses and TLRs are implicated in MS. Here we demonstrate that the synthetic cannabinoid R(+)WIN55,212-2 is a novel regulator of TLR3 and TLR4 signaling by inhibiting the pro-inflammatory signaling axis triggered by TLR3 and TLR4 whilst selectively augmenting TLR3-induced activation of IFN regulatory factor 3 (IRF3) and expression of IFN-β. We present evidence that R(+)WIN55,212-2 strongly promotes the nuclear localization of IRF3. The potentiation of IFN-β ...
http://mural.maynoothuniversity.ie/4267/
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Genome of Acanthamoeba castellanii highlights extensive lateral gene transfer and early evolution of tyrosine kinase signaling
(2013)
Clarke, Michael; Lohan, Amanda; Liu, Bernard; Lagkouvardos, Ilias; Roy, Scott; Zafar, N...
Genome of Acanthamoeba castellanii highlights extensive lateral gene transfer and early evolution of tyrosine kinase signaling
(2013)
Clarke, Michael; Lohan, Amanda; Liu, Bernard; Lagkouvardos, Ilias; Roy, Scott; Zafar, Nikhat; Bertelli, Claire; Schilde, Christina; Kianianmomeni, Arash; Burglin, Thomas R.; Frech, Christian; Turcotte, Bernard; Kopec, Klaus O.; Synnott, John M.; Choo, Caleb; Paponov, Ivan; Finkler, Aliza; Soon Heng Tan, Chris; Hutchins, Andrew P.; Weinmeier, Thomas
Abstract:
Background The Amoebozoa constitute one of the primary divisio ns of eukaryotes encompassing taxa of both biomedic al and evolutionary importance, yet its genomic divers ity remains largely unsampled. Here we present an analysis of a whole genome assembly of Acanthamoeba castellanii ( Ac ) the first representative from a solitary free-living amoebozoan. Results Ac encodes 15,455 compact intron rich genes a signifi cant number of which are predicted to have arisen through interkingdom lateral gene transfer (LGT). A majority of the LGT candidates have undergone a substantial degree of intronization and Ac appears to have incorporated them into established transcriptional programs. Ac manifests a complex signaling and cell communicati on repertoire including a complete tyrosine kinase signaling toolkit and a comparable diversity of predicted extracellular receptors to that found in the facultatively multicellular dictyostelids. An impor tant environmental host of a diverse range of bac...
http://mural.maynoothuniversity.ie/4226/
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Gliotoxin effects on fungal growth: Mechanisms and exploitation
(2012)
Carberry, Stephen; Molloy, Emer; Hammel, Stephen; O'Keefe, Grainne; Jones, Gary W....
Gliotoxin effects on fungal growth: Mechanisms and exploitation
(2012)
Carberry, Stephen; Molloy, Emer; Hammel, Stephen; O'Keefe, Grainne; Jones, Gary W.; Kavanagh, Kevin; Doyle, Sean
Abstract:
Although initially investigated for its antifungal properties, little is actually known about the effect of gliotoxin on Aspergillus fumigatus and other fungi. We have observed that exposure of A. fumigatus to exogenous gliotoxin (14 lg/ml), under gliotoxin-limited growth conditions, results in significant alteration of the expression of 27 proteins (up- and down-regulated >1.9-fold; p < 0.05) including de novo expression of Cu, Zn superoxide dismutase, up-regulated allergen Asp f3 expression and down-regulated catalase and a peroxiredoxin levels. Significantly elevated glutathione GSH levels (p < 0.05), along with concomitant resistance to diamide, were evident in A. fumigatus ∆gliT, lacking gliotoxin oxidoreductase, a gliotoxin self-protection gene. Saccharomyces cerevisiae deletents (∆sod1 and ∆yap1) were hypersensitive to exogenous gliotoxin, while ∆gsh1 was resistant. Significant gliotoxin-mediated (5 µg/ml) growth inhibition (p < 0.001) of Aspergillus nidulans, Asp...
http://mural.maynoothuniversity.ie/4233/
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The effect of temperature on hatch and activity of second-stage juveniles of the root-knot nematode, Meloidogyne minor, an emerging pest in north-west Europe
(2011)
Morris, Karen S.; Horgan, Finbarr G.; Downes, Martin; Griffin, Christine
The effect of temperature on hatch and activity of second-stage juveniles of the root-knot nematode, Meloidogyne minor, an emerging pest in north-west Europe
(2011)
Morris, Karen S.; Horgan, Finbarr G.; Downes, Martin; Griffin, Christine
Abstract:
Meloidogyne minor is a serious threat to turfgrass in north-west Europe, and has a broad host range that includes other economically important plants. The species was described only recently and little is known about its biology. This study examines the effect of temperature on hatch and motility of second-stage juveniles (J2), and records hatching from egg masses collected from golf greens in different seasons. Eggs were present throughout the year and a high percentage hatch (46-88%) was recorded when they were incubated at 20◦C. When egg masses were incubated at constant temperatures, J2 hatched between 15 and 25◦C, with limited hatch (<1%) at 10 and 30◦C. The percentage hatch was lower at 15◦C (43%) than at 20-25◦C (63-76%). J2 hatched fastest at 23◦C, with an average duration to hatching of 7 days compared to 17 days at 15◦C. The range of temperatures at which J2 was active was broader than that at which they hatched. J2 were active from 4-30◦C, with greatest activity betwee...
http://mural.maynoothuniversity.ie/4190/
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Cross-taxa congruence, indicators and environmental gradients in soils under agricultural and extensive land management
(2012)
Keith, Aidan M.; Boots, Bas; Hazard, Christina; Niechoj, Robin; Arroyo, Julio; Bending,...
Cross-taxa congruence, indicators and environmental gradients in soils under agricultural and extensive land management
(2012)
Keith, Aidan M.; Boots, Bas; Hazard, Christina; Niechoj, Robin; Arroyo, Julio; Bending, Gary D.; Bolger, Tom; Breen, John; Clipson, Nicholas; Doohan, Fiona M.; Griffin, Christine; Schmidt, Olaf
Abstract:
Important steps in developing reliable bioindicators for soil quality are characterising soil biodiversity and determining the response of its components to environmental factors across a range of land uses and soil types. Baseline data from a national survey in Ireland were used to explore relationships between diversity and composition of micro-organisms (bacteria, fungi, mycorrhiza), and micro-, meso- and macro-fauna (nematodes; mites; earthworms, ants) across a general gradient representing dominant land uses (arable, pasture, rough-grazing, forest and bogland). These diversity data were also linked to soil physico-chemical properties. Differences in diversity and composition of meso- and macro-fauna, but not microbes, were clear between agriculturally-managed (arable and pasture) and extensivelymanaged (rough-grazing and bogland) soils corresponding to a broad division between ‘mineral’ and ‘organic’ soils. The abundance, richness and composition of nematode and earthworm taxa ...
http://mural.maynoothuniversity.ie/4183/
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The Role of Glutathione S-Transferase GliG in Gliotoxin Biosynthesis in Aspergillus fumigatus
(2011)
Davis, Carol; Carberry, Stephen; Schrettl, Markus; Singh, Ishwar ; Stephens, John C.; B...
The Role of Glutathione S-Transferase GliG in Gliotoxin Biosynthesis in Aspergillus fumigatus
(2011)
Davis, Carol; Carberry, Stephen; Schrettl, Markus; Singh, Ishwar ; Stephens, John C.; Barry, Sarah M.; Kavanagh, Kevin; Challis, Gregory L.; Brougham, Dermot; Doyle, Sean
Abstract:
Gliotoxin, a redox-active metabolite, is produced by the opportunistic fungal pathogen Aspergillus fumigatus, and its biosynthesis is directed by the gli gene cluster. Knowledge of the biosynthetic pathway to gliotoxin, which contains a disulfide bridge of unknown origin, is limited, although L-Phe and L-Ser are known biosynthetic precursors. Deletion of gliG from the gli cluster, herein functionally confirmed as a glutathione S-transferase, results in abrogation of gliotoxin biosynthesis and accumulation of 6-benzyl-6-hydroxy-1-methoxy-3-methylenepiperazine- 2,5-dione. This putative shunt metabolite from the gliotoxin biosynthetic pathway contains an intriguing hydroxyl group at C-6, consistent with a gliotoxin biosynthetic pathway involving thiolation via addition of the glutathione thiol group to a reactive acyl imine intermediate. Complementation of gliG restored gliotoxin production and, unlike gliT, gliG was found not to be involved in fungal self-protection against gliotoxin.
http://mural.maynoothuniversity.ie/4087/
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Simulation of biopsy bevel-tipped needle insertion into soft-gel
(2019)
Jushiddi, Mohamed Gouse; Mulvihill, John J.E.; Chovan, Drahomir; Mani, Aladin; Shanahan...
Simulation of biopsy bevel-tipped needle insertion into soft-gel
(2019)
Jushiddi, Mohamed Gouse; Mulvihill, John J.E.; Chovan, Drahomir; Mani, Aladin; Shanahan, Camelia; Silien, Christophe; Tofail, Syed A.M.; Tiernan, Peter
Abstract:
The full text of this article will not be available in ULIR until the embargo expires on the 22/06/2020
This is a pre-print of an article that was published in " Computers In Biology And Medicine" for the final version please see http://dx.doi.org/10.1016/j.compbiomed.2019.103337
Planning and practice of surgical procedures can be improved through the use of modelling. This study provides an insight into the biopsy needle (i.e. hollow cannula) and needle-tissue interactions using a modelling approach, thus enabling the optimization of needle-tip designs not only for training but also for the planning of surgical procedures. Simulations of needle insertion into agar gel were performed using a Coupled Eulerian-Lagrangian (CEL) based finite element (FE) analysis, adapted for large deformation and tissue fracture. The experimental work covers needle insertion into 3% agar gel using a needle with a beveled tip of various angles, to assess the validity of the simulation....
http://hdl.handle.net/10344/8565
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Multiple pathways involved in palmitic acid-induced toxicity: a system biology approach
(2020)
Osorio, Daniel; Pinzón, Andrés; Martín-Jiménez, Cynthia; Barreto, George E.; González, ...
Multiple pathways involved in palmitic acid-induced toxicity: a system biology approach
(2020)
Osorio, Daniel; Pinzón, Andrés; Martín-Jiménez, Cynthia; Barreto, George E.; González, Janneth
Abstract:
Inflammation is a complex biological response to injuries, metabolic disorders or infections. In the brain, astrocytes play an important role in the inflammatory processes duringneurodegenerativediseases.Recentstudieshaveshownthattheincreaseoffree saturated fatty acids such as palmitic acid produces a metabolic inflammatory response in astrocytes generally associated with damaging mechanisms such as oxidative stress, endoplasmic reticulum stress, and autophagic defects. In this aspect, the synthetic neurosteroid tibolone has shown to exert protective functions against inflammation in neuronal experimental models without the tumorigenic effects exerted by sexual hormones such as estradiol and progesterone. However, there is little information regarding the specific mechanisms of tibolone in astrocytes during inflammatory insults. In the present study, we performed a genome-scale metabolic reconstruction of astrocytes that was used to study astrocytic response during an inflammatory insult b...
http://hdl.handle.net/10344/8614
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HIF-dependent regulation of claudin-1 is central to intestinal epithelial tight junction integrity
(2015)
Saeedi, Bejan J.; Kao, Daniel J.; Kitzenberg, D.A.; Dobrinskikh, Evgenia; Schwisow, Kay...
HIF-dependent regulation of claudin-1 is central to intestinal epithelial tight junction integrity
(2015)
Saeedi, Bejan J.; Kao, Daniel J.; Kitzenberg, D.A.; Dobrinskikh, Evgenia; Schwisow, Kayla D.; Masterson, Joanne C.; Kendrick, Agnieszka A.; Kelly, Caleb J.; Bayless, A.; Kominsky, Douglas J.; Campbell, Eric L.; Kuhn, Kristine A.; Furuta, Glenn T.; Colgan, S.P.; Glover, Louise
Abstract:
Intestinal epithelial cells (IECs) are exposed to profound fluctuations in oxygen tension and have evolved adaptive transcriptional responses to a low-oxygen environment. These adaptations are mediated primarily through the hypoxia-inducible factor (HIF) complex. Given the central role of the IEC in barrier function, we sought to determine whether HIF influenced epithelial tight junction (TJ) structure and function. Initial studies revealed that short hairpin RNA–mediated depletion of the HIF1β in T84 cells resulted in profound defects in barrier and nonuniform, undulating TJ morphology. Global HIF1α chromatin immunoprecipitation (ChIP) analysis identified claudin-1 (CLDN1) as a prominent HIF target gene. Analysis of HIF1β-deficient IEC revealed significantly reduced levels of CLDN1. Overexpression of CLDN1 in HIF1β-deficient cells resulted in resolution of morphological abnormalities and restoration of barrier function. ChIP and site-directed mutagenesis revealed prominent hypoxia ...
http://mural.maynoothuniversity.ie/12486/
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Eosinophils, probiotics, and the microbiome
(2016)
Rosenberg, Helene F.; Masterson, Joanne C.; Furuta, Glenn T.
Eosinophils, probiotics, and the microbiome
(2016)
Rosenberg, Helene F.; Masterson, Joanne C.; Furuta, Glenn T.
Abstract:
There is currently substantial interest in the therapeutic properties of probiotic microorganisms as recent research suggests that oral administration of specific bacterial strains may reduce inflammation and alter the nature of endogenous microflora in the gastrointestinal tract. Eosinophils are multifunctional tissue leukocytes, prominent among the resident cells of the gastrointestinal mucosa that promote local immunity. Recent studies with genetically altered mice indicate that eosinophils not only participate in maintaining gut homeostasis, but that the absence of eosinophils may have significant impact on the nature of the endogenous gut microflora and responses to gut pathogens, notably Clostridium difficile. Furthermore, in human subjects, there is an intriguing relationship between eosinophils, allergic inflammation, and the nature of the lung microflora, notably a distinct association between eosinophil infiltration and detection of bacteria of the phylum Actinobacteria. A...
http://mural.maynoothuniversity.ie/12477/
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More Than a Repair Enzyme: Aspergillus nidulans Photolyase-like CryA Is a Regulator of Sexual Development
(2008)
Bayram, Ozgur; Biesemann, Christoph; Krappmann, Sven; Galland, Paul; Braus, Gerhard H.
More Than a Repair Enzyme: Aspergillus nidulans Photolyase-like CryA Is a Regulator of Sexual Development
(2008)
Bayram, Ozgur; Biesemann, Christoph; Krappmann, Sven; Galland, Paul; Braus, Gerhard H.
Abstract:
Cryptochromes are blue-light receptors that have presumably evolved from the DNA photolyase protein family, and the genomes of many organisms contain genes for both types of molecules. Both protein structures resemble each other, which suggests that light control and light protection share a common ancient origin. In the genome of the filamentous fungus Aspergillus nidulans, however, only one cryptochrome/photolyase-encoding gene, termed cryA, was identified. Deletion of the cryA gene triggers sexual differentiation under inappropriate culture conditions and results in up-regulation of transcripts encoding regulators of fruiting body formation. CryA is a protein whose N- and C-terminal synthetic green fluorescent protein fusions localize to the nucleus. CryA represses sexual development under UVA350-370 nm light both on plates and in submerged culture. Strikingly, CryA exhibits photorepair activity as demonstrated by heterologous complementation of a DNA repair-deficient Escherichia...
http://mural.maynoothuniversity.ie/7183/
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Autophagy mediates epithelial cytoprotection in Eosinophilic Oesophagitis
(2017)
Whelan, Kelly A.; Merves, Jamie F.; Giroux, Veronique; Tanaka, Koji; Guo, Andy; Chandra...
Autophagy mediates epithelial cytoprotection in Eosinophilic Oesophagitis
(2017)
Whelan, Kelly A.; Merves, Jamie F.; Giroux, Veronique; Tanaka, Koji; Guo, Andy; Chandramouleeswaran, Prasanna M.; Benitez, Benitez; Dods, Kara; Que, Jianwen; Masterson, Joanne C.; Fernando, Shahan D.; Godwin, Bridget C.; Klein-Szanto, Andres J.; Chikwava, Kudakwashe; Ruchelli, Eduardo D.; Hamilton, Kathryn E.; Muir, Amanda B.; Wang, Mei-Lun; Furuta, Glenn T.; Falk, Gary W.
Abstract:
Objective—The influence of eosinophilic oesophagitis (EoE)-associated inflammation upon oesophageal epithelial biology remains poorly understood. We investigated the functional role of autophagy in oesophageal epithelial cells (keratinocytes) exposed to the inflammatory EoE milieu. Design—Functional consequences of genetic or pharmacological autophagy inhibition were assessed in endoscopic oesophageal biopsies, human oesophageal keratinocytes, single cell-derived ex vivo murine oesophageal organoids as well as a murine model recapitulating EoE-like inflammation and basal cell hyperplasia. Gene expression, morphological and functional characterization of autophagy and oxidative stress were performed by transmission electron microscopy, immunostaining, immunoblotting, live cell imaging and flow cytometry. Results—EoE-relevant inflammatory conditions promoted autophagy and basal cell hyperplasia in three independent murine EoE models and oesophageal organoids. Inhibition of autophagic ...
http://mural.maynoothuniversity.ie/11827/
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Hepatitis C virus (HCV)-induced suppressor of cytokine signaling (SOCS) 3 regulates proinflammatory TNF-α responses
(2014)
Collins, Aideen S.; Ahmed, Suaad; Napoletano, Silvia; Schroeder, Martina; Johnston, Jam...
Hepatitis C virus (HCV)-induced suppressor of cytokine signaling (SOCS) 3 regulates proinflammatory TNF-α responses
(2014)
Collins, Aideen S.; Ahmed, Suaad; Napoletano, Silvia; Schroeder, Martina; Johnston, James A.; Hegarty, John E.; O'Farrelly, Cliona; Stevenson, Nigel J.
Abstract:
TNF-α is a proinflammatory cytokine, dramatically elevated during pathogenic infection and often responsible for inflammation-induced disease pathology. SOCS proteins are inhibitors of cytokine signaling and regulators of inflammation. In this study, we found that both SOCS1 and SOCS3 were transiently induced by TNF-α and negatively regulate its NF-κB-mediated signal transduction. We discovered that PBMCs from HCV-infected patients have elevated endogenous SOCS3 expression but less TNF-α-mediated IκB degradation and proinflammatory cytokine production than healthy controls. HCV protein expression in Huh7 hepatocytes also induced SOCS3 and directly inhibited TNF-α-mediated IL-8 production. Furthermore, we found that SOCS3 associates with TRAF2 and inhibits TRAF2-mediated NF-κB promoter activity, suggesting a mechanism by which SOCS3 inhibits TNF-α-mediated signaling. These results demonstrate a role for SOCS3 in regulating proinflammatory TNF-α signal transduction and reveal a novel ...
http://mural.maynoothuniversity.ie/6918/
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NK cells regulate CXCR2+ neutrophil recruitment during acute lung injury
(2017)
Hoegl, Sandra; Ehrentraut, Heidi; Brodsky, Kelley S.; Victorino, Francisco; Golden‐Maso...
NK cells regulate CXCR2+ neutrophil recruitment during acute lung injury
(2017)
Hoegl, Sandra; Ehrentraut, Heidi; Brodsky, Kelley S.; Victorino, Francisco; Golden‐Mason, Lucy; Eltzschig, Holger K.; McNamee, Eóin N.
Abstract:
A critical step in the pathogenesis of acute lung injury (ALI) is excessive recruitment of polymorphonuclear neutrophils (PMNs) into the lungs, causing significant collateral tissue damage. Defining the molecular and cellular steps that control neutrophil infiltration and activation during ALI is therefore of important therapeutic relevance. Based on previous findings implicating the transcription factor Tbet in mucosal Th1‐inflammation, we hypothesized a detrimental role for Tbet during ALI. In line with our hypothesis, initial studies of endotoxin‐induced lung injury revealed a marked protection of Tbet−/− mice, including attenuated neutrophilia compared to WT counterparts. Surprisingly, subsequent studies identified natural killer (NK) cells as the major source of pulmonary Tbet during ALI. In addition, a chemokine screen suggested that mature Tbet+ NK‐cells are critical for the production of pulmonary CXCL1 and ‐2, thereby contributing to pulmonary PMN recruitment. Indeed, both ...
http://mural.maynoothuniversity.ie/11659/
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Nuclear Factor κB2 p52 Protein Has a Role in Antiviral Immunity through IκB Kinase ϵ-dependent Induction of Sp1 Protein and Interleukin 15
(2013)
Doyle, Sarah L.; Shirey, Kari Ann; McGettrick, Anne F.; Kenny, Elaine F.; Carpenter, Su...
Nuclear Factor κB2 p52 Protein Has a Role in Antiviral Immunity through IκB Kinase ϵ-dependent Induction of Sp1 Protein and Interleukin 15
(2013)
Doyle, Sarah L.; Shirey, Kari Ann; McGettrick, Anne F.; Kenny, Elaine F.; Carpenter, Susan B.; Caffrey, Brian E.; Gargan, Siobhan; Quinn, Susan R.; Caamano, Jorge H.; Moynagh, Paul N.; Vogel, Stefanie N.; O'Neill, Luke A.
Abstract:
In this study we describe a previously unreported function for NFκB2, an NFκB family transcription factor, in antiviral immunity. NFκB2 is induced in response to poly(I:C), a mimic of viral dsRNA. Poly(I:C), acting via TLR3, induces p52-dependent transactivation of a reporter gene in a manner that requires the kinase activity of IκB kinase ϵ (IKKϵ) and the transactivating potential of RelA/p65. We identify a novel NFκB2 binding site in the promoter of the transcription factor Sp1 that is required for Sp1 gene transcription activated by poly(I:C). We show that Sp1 is required for IL-15 induction by both poly(I:C) and respiratory syncytial virus, a response that also requires NFκB2 and IKKϵ. Our study identifies NFκB2 as a target for IKKϵ in antiviral immunity and describes, for the first time, a role for NFκB2 in the regulation of gene expression in response to viral infection.
http://mural.maynoothuniversity.ie/11035/
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Environmental stress resistance: Selection in plant cell cultures.
(1980)
Dix, Philip
Environmental stress resistance: Selection in plant cell cultures.
(1980)
Dix, Philip
Abstract:
The selection of variant lines in plant cell cultures has expanded to such an extent that it is no longer easy to review the subject in its entirety. The most recent and comprehensive review1 covers the variant cell lines which had been described by the beginning of 1979. The purpose of this report is to look at the progress in the selection of cell lines resistant to various environmental stresses. The rationale behind the selection of this kind of variant is generally practical, the objective bei11g to obtain cultivars of crop plants with a greater tolerance to adverse climatic o~ soil conditions. A further potential value of resistant cell lines for studies on the nature of stress sensitivity and resistance will also be emphasise-d here. Cell lines resistant to several different stresses have been described and these are considered in the following sections.
http://mural.maynoothuniversity.ie/9783/
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Antibiotic resistance in Nicotiana.
(1980)
Maliga, Pal; Xuan, Le Thi; Dix, Philip; Cseplo, Agnes
Antibiotic resistance in Nicotiana.
(1980)
Maliga, Pal; Xuan, Le Thi; Dix, Philip; Cseplo, Agnes
Abstract:
The mode of action, and mechanism of resistance of many antibiotics are known since antibiotic resistance markers are commonly used in microbial genetics. Some of them, such as streptomycin, kanamycin and chloramphenicol selectively inhibit protein synthesis on the ''bacterial type'' ribosomes of the chloroplasts and mitochondria. Resistance to these antibiotics is, in some cases, coded by the organellar DNA, so these mutations are convenient markers in studies on organelle segregation, recombination and function in fungi and a 1 gae 1 The need for marker mutations in plant cell genetics, and our interest in cytoplasmic organelles, suggested to us the selection of antibiotic resistant cell lines in cell cultures of two species belonging to the genus Nicotiana~ N. tabacum and N. sylvestris. Streptomycin, kanamycin and chloramphenicol resistant lines described in flowering plants (N. tabacum~ N. sylvestris~ Petunia hybrida) and the moss, Physcomitrella patens~ have...
http://mural.maynoothuniversity.ie/9749/
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Fasciola hepatica cathepsin L-like proteases: biology, function, and potential in the development of first generation liver fluke vaccines
(2003)
Dalton, John P.; O'Neill, Sandra M.; Stack, Colin M.; Collins, Peter R.; Walshe, A...
Fasciola hepatica cathepsin L-like proteases: biology, function, and potential in the development of first generation liver fluke vaccines
(2003)
Dalton, John P.; O'Neill, Sandra M.; Stack, Colin M.; Collins, Peter R.; Walshe, Alan; Sekiya, Mary; Doyle, Sean; Mulcahy, Grace; Hoyle, Deborah; Khaznadji, Eric; Moire, Nathalie; Brennan, Gerard; Mousley, Angela; Kreshchenko, Natalia; Maule, Aaron G.; Donnelly, Sheila M.
Abstract:
Fasciola hepatica secretes cathepsin L proteases that facilitate the penetration of the parasite through the tissues of its host, and also participate in functions such as feeding and immune evasion. The major proteases, cathepsin L1 (FheCL1) and cathepsin L2 (FheCL2) are members of a lineage that gave rise to the human cathepsin Ls, Ks and Ss, but while they exhibit similarities in their substrate specificities to these enzymes they differ in having a wider pH range for activity and an enhanced stability at neutral pH. There are presently 13 Fasciola cathepsin L cDNAs deposited in the public databases representing a gene family of at least seven distinct members, although the temporal and spatial expression of each of these members in the developmental stage of F. hepatica remains unclear. Immunolocalisation and in situ hybridisation studies, using antibody and DNA probes, respectively, show that the vast majority of cathepsin L gene expression is carried out in the epithelial cell...
http://mural.maynoothuniversity.ie/7404/
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The Relation between the What-It-Is and the Why-It-Is in Aristotle's Posterior Analytics, On the Parts of Animals, and Metaphysics
(2020)
GE, TIANQIN
The Relation between the What-It-Is and the Why-It-Is in Aristotle's Posterior Analytics, On the Parts of Animals, and Metaphysics
(2020)
GE, TIANQIN
Abstract:
In this dissertation, my aim is to answer the following main question: 'What is the relation between the what-it-is and the why-it-is in Aristotle?' I focus on Aristotle's three treatises: Posterior Analytics, On the Parts of Animals, and Metaphysics. The answer I will defend in this thesis can be formulated as follows: 1. In the Posterior Analytics, the enquiry into the what-it-is is inter-transformable to the enquiry into the why-it-is (This is what I call 'the Analytics Model'). 2. In the Parts of Animals, the enquiry into the what-it-is depends on the enquiry into the why-it-is, but the enquiry into the why-it-is need not depend on the enquiry into the what-it-is (This I regard as 'the Biology Model'). 3. In Metaphysics ZH, the final enquiry into the what-it-is depends on the enquiry into the why-it-is, and the enquiry into the why-it-is further depends on earlier enquiry into the what-it-is (This is 'the Metaphysics Model'). 4. The A...
http://hdl.handle.net/2262/92335
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A rational computer-aided drug discovery approach to target IRE1 and PERK: Insights into structural dynamics and selectivity
(2020)
Chintha, Chetan
A rational computer-aided drug discovery approach to target IRE1 and PERK: Insights into structural dynamics and selectivity
(2020)
Chintha, Chetan
Abstract:
Cells constantly monitor the number of misfolded proteins they accumulate. The accumulation of misfolded proteins in the endoplasmic reticulum (ER) triggers an evolutionarily conserved signaling pathway called the unfolded protein response (UPR). Inositol-requiring enzyme 1 (IRE1), PKR-like endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6) are the main UPR signal transducers. IRE1α and PERK were characterized using a chemical biology approach. Primarily, computational analysis of druggable sites of IRE1α and PERK was carried out. We performed docking studies to understand the selectivity of PERK kinase inhibitors. Additionally, KIT was identified as a common non-specific target of UPR kinase inhibitors kinase inhibiting RNase attenuator 6 (KIRA6) and GSK2606414 (GSK414). We analyzed the IRE1α RNase pocket for the suitability of structure-based drug screening. Further, we looked at how an IRE1α kinase inhibitor impacted the different dimer forms using ...
http://hdl.handle.net/10379/15977
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The actinin family of actin crosslinking proteins: natural functions and potential applications in synthetic biology
(2016)
Murphy, Anita Catherine Honor
The actinin family of actin crosslinking proteins: natural functions and potential applications in synthetic biology
(2016)
Murphy, Anita Catherine Honor
Abstract:
Actinin and spectrin proteins are members of the Spectrin Family of Actin Crosslinking Proteins. The importance of these proteins in the cytoskeleton is demonstrated by the fact that they are common targets for disease causing mutations. In their most prominent roles, actinin and spectrin are responsible for stabilising and maintaining the muscle architecture during contraction, and providing shape and elasticity to the red blood cell in circulation, respectively. To carry out such roles, actinin and spectrin must possess important mechanical and physical properties. These attributes are desirable when choosing a building block for protein-based nanoconstruction. In this study, I assess the contribution of several disease-associated mutations in the actinin-1 actin binding domain that have recently been linked to a rare platelet disorder, congenital macrothrombocytopenia. I investigate the suitability of both actinin and spectrin proteins as potential building blocks for nanoscale s...
http://hdl.handle.net/10468/3314
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Whole blood gene expression profiling of neonates with confirmed bacterial sepsis
(2020)
Dickinson, Paul; Smith, Claire L.; Forster, Thorsten; Craigon, Marie; Ross, Alan J.; Kh...
Whole blood gene expression profiling of neonates with confirmed bacterial sepsis
(2020)
Dickinson, Paul; Smith, Claire L.; Forster, Thorsten; Craigon, Marie; Ross, Alan J.; Khondoker, Mizan R.; Ivens, Alasdair; Lynn, David J.; Orme, Judith; Jackson, Allan; Lacaze, Paul; Flanagan, Katie L.; Stenson, Benjamin J.; Ghazal, Peter
Abstract:
Neonatal infection remains a primary cause of infant morbidity and mortality worldwide and yet our understanding of how human neonates respond to infection remains incomplete. Changes in host gene expression in response to infection may occur in any part of the body, with the continuous interaction between blood and tissues allowing blood cells to act as biosensors for the changes. In this study we have used whole blood transcriptome profiling to systematically identify signatures and the pathway biology underlying the pathogenesis of neonatal infection. Blood samples were collected from neonates at the first clinical signs of suspected sepsis alongside age matched healthy control subjects. Here we report a detailed description of the study design, including clinical data collected, experimental methods used and data analysis workflows and which correspond with data in Gene Expression Omnibus (GEO) data sets (GSE25504). Our data set has allowed identification of a patient invariant ...
http://hdl.handle.net/11019/2288
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Non-photopic and photopic visual cycles differentially regulate immediate, early and late-phases of cone photoreceptor-mediated vision
(2020)
Ward, Rebecca; Kaylor, Joanna J.; Cobice, Diego F.; Pepe, Dionissia A.; McGarrigle, Eog...
Non-photopic and photopic visual cycles differentially regulate immediate, early and late-phases of cone photoreceptor-mediated vision
(2020)
Ward, Rebecca; Kaylor, Joanna J.; Cobice, Diego F.; Pepe, Dionissia A.; McGarrigle, Eoghan M.; Kennedy, Breandán; et al.
Abstract:
Cone photoreceptors in the retina enable vision over a wide range of light intensities. However, the processes enabling cone vision in bright light (i.e. photopic vision) are not adequately understood. Chromophore regeneration of cone photopigments may require the retinal pigment epithelium (RPE) and/or retinal Müller glia. In the RPE, isomerization of all-trans-retinyl esters (atRE) to 11-cis-retinol (11cROL) is mediated by the retinoid isomerohydrolase Rpe65. A putative alternative retinoid isomerase, dihydroceramide desaturase-1 (DES1), is expressed in RPE and Müller cells. The retinol-isomerase activities of Rpe65 and Des1 are inhibited by emixustat and fenretinide, respectively. Here, we tested the effects of these visual cycle inhibitors on immediate, early and late phases of cone photopic vision. In zebrafish larvae raised under cyclic light conditions, fenretinide impaired late cone photopic vision, whereas emixustat-treated zebrafish unexpectedly had normal vision. In contr...
http://hdl.handle.net/10197/11496
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Advances in astrocyte computational models: from metabolic reconstructions to multi-omic approaches
(2020)
González, Janneth; Pinzón, Andrés; Angarita-Rodríguez, Andrea; Aristizaba, Andrés Felip...
Advances in astrocyte computational models: from metabolic reconstructions to multi-omic approaches
(2020)
González, Janneth; Pinzón, Andrés; Angarita-Rodríguez, Andrea; Aristizaba, Andrés Felipe; Barreto, George E.; Martín-Jiménez, Cynthia
Abstract:
The growing importance of astrocytes in the field of neuroscience has led to a greater number of computational models devoted to the study of astrocytic functions and their metabolic interactions with neurons. The modeling of these interactions demands a combined understanding of brain physiology and the development of computational frameworks based on genomic-scale reconstructions, system biology, and dynamic models. These computational approaches have helped to highlight the neuroprotective mechanisms triggered by astrocytes and other glial cells, both under normal conditions and during neurodegenerative processes. In the present review, we evaluate some of the most relevant models of astrocyte metabolism, including genome-scale reconstructions and astrocyte-neuron interactions developed in the last few years. Additionally, we discuss novel strategies from the multi-omics perspective and computational models of other glial cell types that will increase our knowledge in brain...
http://hdl.handle.net/10344/9194
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Does the scion or rootstock of Citrus sp. affect the feeding and biology of Diaphorina citri Kuwayama (Hemiptera: Liviidae)?
(2018)
Alves Rodrigues, Gustavo; Beloti, Victor Hugo; Faggioni-Floriano, Kenya Martins; de Car...
Does the scion or rootstock of Citrus sp. affect the feeding and biology of Diaphorina citri Kuwayama (Hemiptera: Liviidae)?
(2018)
Alves Rodrigues, Gustavo; Beloti, Victor Hugo; Faggioni-Floriano, Kenya Martins; de Carvalho, Sergio Alves; de Andrade Moral, Rafael; Borges Demetrio, Clarice Garcia; Postali Parra, Jose Roberto; Yamamoto, Pedro Takao
Abstract:
The Asian citrus psyllid (ACP) Diaphorina citri is the main vector of the bacteria associated with Huanglongbing, and can exploit more than 50 species of the family Rutaceae as hosts. The number of possible hosts is even higher if plant varieties are included. This study evaluated the influence of different combinations of scion and rootstock citrus varieties on the development and feeding of ACP. Survival rates for the egg stage were highest on the Valencia and Sicilian varieties, both grafted on Sunki mandarin, with means of 87.99 and 87.98%, respectively; and lowest (67.63%) on Hamlin 9 Rangpur lime. The lowest levels of both nymphal and total viability (egg-adult) were obtained on Hamlin, regardless of the rootstock used. The total development time (egg-adult) ranged from 17.92 to 19.33 days for the Peˆra 9 Sunki and Hamlin 9 Swingle combinations, respectively. Cluster analysis separated the hosts into two groups, the first consisting of the combinations of the Hamlin variety, a...
http://mural.maynoothuniversity.ie/13260/
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