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Displaying Results 176 - 200 of 2088 on page 8 of 84
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Advances in the Development of Non-steroidal Mineralocorticoidreceptor Antagonists
(2019)
Pérez-Gordillo, Felipe L; Jesús Pérez de Vega,, Maria; Gerona-Navarro, Guillermo; Rodrí...
Advances in the Development of Non-steroidal Mineralocorticoidreceptor Antagonists
(2019)
Pérez-Gordillo, Felipe L; Jesús Pérez de Vega,, Maria; Gerona-Navarro, Guillermo; Rodríguez, Yoel; Alvarez de la Rosa, Diego; González-Muñiz, Rosario; Martín-Martínez, Mercedes
Abstract:
<p>The original book chapter is available at https://www.intechopen.com/</p>
<p>Aldosterone plays an important role in the regulation of blood pressure, body fluid, and electrolyte homeostasis. Overactivation of aldosterone/mineralocorticoid receptor (MR) pathway leads to hypertension, atherosclerosis, vascular damage, heart failure, and chronic kidney disease and is involved in many other diseases associated with endothelial dysfunction, inflammation, fibrosis, and metabolic disorders. Aldosterone is a final product of the renin-angiotensin-aldosterone system (RAAS), and its production is activated by angiotensin II, while angiotensin-(1–7) negatively regulates angiotensin II-mediated aldosterone production and in some experimental models inhibits aldosterone-induced damage in target tissues. In fact, the aldosterone/mineralocorticoid receptor-dependent pathway is regulated upstream by at least two major axes of RAAS: classical axis (ACE/Ang II) and nonclassic...
https://epubs.rcsi.ie/molmedart/47
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Potential Benefit of Mineralocorticoid Receptor Antagonists in Kidney Diseases
(2019)
Barrera-Chimal, Jonatan
Potential Benefit of Mineralocorticoid Receptor Antagonists in Kidney Diseases
(2019)
Barrera-Chimal, Jonatan
Abstract:
<p>The original book chapter is available at https://www.intechopen.com/</p>
<p>Since the last two decades, a major paradigm shift occurred in our understanding of the physiological and pathophysiological roles of the mineralocorticoid receptor (MR). Expression of the MR in cells/tissues not involved in sodium/potassium balance and extracellular volume homeostasis, i.e., the primary role of the aldosterone/MR complex, paved the way to the discovery of unsuspected implications of MR in a variety of cellular processes and pathological consequences. It also opens the possibility for quick translation to the bedside using available MR antagonists (MRAs) such as spironolactone, canrenone, or eplerenone or using the more recently developed various nonsteroidal MRAs that are not yet marketed. Landmark clinical trials like RALES, EPHESUS, or EMPHASIS well established that MRAs provide great benefits in patients with heart failure and spironolactone or eplerenone have b...
https://epubs.rcsi.ie/molmedart/50
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Primary Aldosteronism: A Glimpse into the Most Common Endocrine Cause of Arterial Hypertension
(2019)
Rossi, Gian Paulo; Seccia, Teresa M
Primary Aldosteronism: A Glimpse into the Most Common Endocrine Cause of Arterial Hypertension
(2019)
Rossi, Gian Paulo; Seccia, Teresa M
Abstract:
<p>The original book chapter is available at https://www.intechopen.com/</p>
<p>Compelling evidences showed that primary aldosteronism (PA) is a quite common disease. In spite of this, hypertensive patients are seldom screened for PA and, therefore, many patients are mislabelled as (low-renin) essential hypertension thereby remaining exposed to the nefarious consequences of long-term hyperaldosteronism. In this chapter we reviewed the clinical aspects of PA and the evidences supporting the need of implementing strategies aimed at diagnosing early PA patients. After reporting the prevalence rates of PA in different cohorts of hypertensive patients, we examined the reasons why PA is rarely searched for. The cardiovascular and renal damage associated with PA were also discussed, with particular emphasis to endothelial dysfunction, vascular remodeling, left ventricular changes, fibrosis, diastolic dysfunction, atrial fibrillation and chronic kidney disease. Studies...
https://epubs.rcsi.ie/molmedart/49
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Renin-Angiotensin-Aldosterone System in Heart Failure: Focus on Nonclassical Angiotensin Pathways as Novel Upstream Targets Regulating Aldosterone
(2019)
Tyrankiewicz, Urszula; Kij, Agnieszka; Mohaissen, Tasnim; Olkowicz, Mariola; Smolenski,...
Renin-Angiotensin-Aldosterone System in Heart Failure: Focus on Nonclassical Angiotensin Pathways as Novel Upstream Targets Regulating Aldosterone
(2019)
Tyrankiewicz, Urszula; Kij, Agnieszka; Mohaissen, Tasnim; Olkowicz, Mariola; Smolenski, Ryszard T; Chlopicki, Stefan
Abstract:
<p>The original book chapter is available at https://www.intechopen.com/</p>
<p>Aldosterone plays an important role in the regulation of blood pressure, body fluid, and electrolyte homeostasis. Overactivation of aldosterone/mineralocorticoid receptor (MR) pathway leads to hypertension, atherosclerosis, vascular damage, heart failure, and chronic kidney disease and is involved in many other diseases associated with endothelial dysfunction, inflammation, fibrosis, and metabolic disorders. Aldosterone is a final product of the renin-angiotensin-aldosterone system (RAAS), and its production is activated by angiotensin II, while angiotensin-(1–7) negatively regulates angiotensin II-mediated aldosterone production and in some experimental models inhibits aldosterone-induced damage in target tissues. In fact, the aldosterone/mineralocorticoid receptor-dependent pathway is regulated upstream by at least two major axes of RAAS: classical axis (ACE/Ang II) and nonclassic...
https://epubs.rcsi.ie/molmedart/48
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Science classroom discourse and learning in secondary biology classrooms implementing a Content and Language Integrated Learning (CLIL) approach
(2019)
Tagnin, Laura
Science classroom discourse and learning in secondary biology classrooms implementing a Content and Language Integrated Learning (CLIL) approach
(2019)
Tagnin, Laura
Abstract:
This multiple case study research analyses upper secondary teachers’ and students’ experiences of learning biology through the medium of a foreign language, which in this study is English, in the European context (German and Italy). This instructional approach has been named Content and Language Integrated Learning (CLIL). So far, the focus of research into CLIL has been mainly on language. When looking at content (science, in this study) research into CLIL has tended to adopt a language learning orientation in design, analytical tools and theoretical orientation. Furthermore, findings on content learning are overall inconclusive. Specifically, when examining science learning, research results are extremely scarce and often published in languages other than English. Leading on from this, the aim of this study is to contribute to the science teaching practice by filling the evidenced gap with a deeper understanding of science learning when a CLIL approach is implemented. Three case ...
http://hdl.handle.net/10379/15530
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Aldosterone Regulation of Protein Kinase Signaling Pathways and Renal Na+ Transport by Non-genomic Mechanisms
(2019)
Thomas, Warren; Harvey, Brian
Aldosterone Regulation of Protein Kinase Signaling Pathways and Renal Na+ Transport by Non-genomic Mechanisms
(2019)
Thomas, Warren; Harvey, Brian
Abstract:
<p>The original book chapter is available at https://www.intechopen.com/</p>
<p>Aldosterone is the key regulating hormone of whole-body fluid and electrolyte homeostasis. Perturbations in aldosterone synthesis and over-activation of the mineralocorticoid receptor (MR) can lead to excess salt reabsorption and hypertension. The cortical collecting duct (CCD) is the main site of action in the kidney for aldosterone regulation of whole-body sodium homeostasis through actions on the epithelial sodium channel (ENaC) and the Na/K-ATPase (Na/K pump). Aldosterone stimulates ENaC trafficking into the apical cell membranes in the CCD and enhances channel stability and open probability, as well as activating the basolateral membrane Na/K pump to produce an overall increase in the transepithelial reabsorption of sodium. Aldosterone/MR regulates the activity of ENaC in the CCD through both rapid non-genomic (secs-mins) and latent genomic (hours-days) signaling pathways. Thes...
https://epubs.rcsi.ie/molmedart/58
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COLT: A New Weapon to Disseminate Knowledge
(2019)
Rossier, Bernard C; Rossier, Michelle; Kraehenbühl, Jean-Pierre
COLT: A New Weapon to Disseminate Knowledge
(2019)
Rossier, Bernard C; Rossier, Michelle; Kraehenbühl, Jean-Pierre
Abstract:
<p>The original book chapter is available at https://www.intechopen.com/</p>
<p>Too few researchers receive adequate pre- or postgraduate training to conduct a rigorous scientific study. In the digital age, new tools are emerging, and the development of distance education could improve this worrying situation. In this context, Health Science e-Training (HSeT), a nonprofit Swiss foundation, has developed new pedagogical concepts and tools under customized online training (COLT). For the ADMIRE Cost network, we have used an article-based e-learning (ABL) tool that allowed the students to learn how to read in depth and critically a scientific article and to rigorously address the problem of scientific reproducibility. The evaluation of the program by the students and the tutors has been quite positive. In conclusion COLT was well adapted to the needs of the ADMIRE Cost Action, a European network in which students from countries separated by thousands of miles can ...
https://epubs.rcsi.ie/molmedart/59
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MicroRNAs in Aldosterone Production and Action
(2019)
MacKenzie, Scott M; van Kralingen, Josie; Martin, Hannah
MicroRNAs in Aldosterone Production and Action
(2019)
MacKenzie, Scott M; van Kralingen, Josie; Martin, Hannah
Abstract:
<p>The original book chapter is available at https://www.intechopen.com/</p>
<p>The secretion of aldosterone by the adrenal cortex is a tightly regulated process. Loss of this control can result in severe hypertension and end-organ damage, so detailed understanding of the various mechanisms by which the body regulates aldosterone biosynthesis is key. The emergence of microRNAs (miRNAs) as negative regulators of numerous physiological processes has naturally led to their study in the context of aldosterone production. We summarise several studies that have demonstrated a significant role for microRNAs in aldosterone biosynthesis and action, thereby presenting a possible therapeutic role in the treatment of common forms of hypertension such as primary aldosteronism. Furthermore, the presence of microRNAs in the circulation offers the prospect of accessible and informative biomarkers that may simplify the currently protracted and technically difficult diagnosis of...
https://epubs.rcsi.ie/molmedart/56
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Post-Translational Modification of MR Activity
(2019)
Alvarez de la Rosa, Diego; Serrano-Morillas, Natalia
Post-Translational Modification of MR Activity
(2019)
Alvarez de la Rosa, Diego; Serrano-Morillas, Natalia
Abstract:
<p>The original book chapter is available at https://www.intechopen.com/</p>
<p>The mineralocorticoid receptor (MR) is a ligand-activated transcription factor that transduces the effects of aldosterone and glucocorticoids in a tissue- and cell type-specific ways. Differential regulation of MR by post-translational modifications (PTMs) has been proposed to play a key role in modulating its function. In addition, modifications of other proteins that physically or functionally interact with MR add an additional layer of regulation to aldosterone or glucocorticoid signaling. In this chapter, we will summarize the main post-translational modifications of MR described so far, discussing their possible implications in the physiological and pathological roles of the receptor. We will also discuss post-translational modulation of other proteins impacting MR function such as heat shock protein 90 or 11ß-hydroxysteroid dehydrogenase type 2.</p>
https://epubs.rcsi.ie/molmedart/57
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View on Aldosterone and the Brain Revisited
(2019)
Hlavacova, Natasa; Jezova, Damiela
View on Aldosterone and the Brain Revisited
(2019)
Hlavacova, Natasa; Jezova, Damiela
Abstract:
<p>The original book chapter is available at https://www.intechopen.com/</p>
<p>The mineralocorticoid hormone aldosterone has been investigated almost exclusively with respect to cardiovascular function, as the main effects of aldosterone are related to water-electrolyte balance and the control of the blood pressure. This overview is focused on less traditional and long-time neglected effects of aldosterone on the brain and behavior. Preclinical studies by our research group brought evidence on causal relationships between aldosterone and anxiety as well as aldosterone and depression-like behavior. Aldosterone was found to be anxiogenic and depressogenic in a rat model. Preclinical studies also indicate that aldosterone may be an early marker of depression onset. Aldosterone is known to be an important component of the stress response, and we have shown that its role is particularly important during early postnatal period in pups. Studies in patients with major...
https://epubs.rcsi.ie/molmedart/54
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Transcriptional Regulation and Epigenetics in Cardiovascular Cells: Role of the Mineralocorticoid Receptor
(2019)
Deng, Lisa; Hein, Lutz; Lother, Achim
Transcriptional Regulation and Epigenetics in Cardiovascular Cells: Role of the Mineralocorticoid Receptor
(2019)
Deng, Lisa; Hein, Lutz; Lother, Achim
Abstract:
<p>The original book chapter is available at https://www.intechopen.com/</p>
<p>The mineralocorticoid receptor (MR), a ligand-activated transcription factor, plays an important role in the pathophysiology of cardiovascular disease. Epigenetic mechanisms such as DNA methylation or histone modifications in addition to the DNA sequence are decisive regulators of cell type-specific transcriptional activity and gene expression by controlling chromatin accessibility. In this review, we summarise the current knowledge about the impact of MR on gene expression in cardiovascular cells. We discuss studies investigating the interaction of MR with epigenetic mechanisms or other transcription factors and their implications for the cardiovascular system. Finally, we compare mechanisms of transcriptional regulation by MR and other nuclear transcription factors. In conclusion, MR is an important regulator of gene expression in cardiovascular cells. Potential mechanisms of cell...
https://epubs.rcsi.ie/molmedart/55
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Mineralocorticoid Receptor in Novel Target Tissues: A Closer Look at the Adipocyte
(2019)
Armani, Andrea; Marzolla, Vincenzo; Feraco, Alessandra; Gorini, Stefania; Mammi, Cateri...
Mineralocorticoid Receptor in Novel Target Tissues: A Closer Look at the Adipocyte
(2019)
Armani, Andrea; Marzolla, Vincenzo; Feraco, Alessandra; Gorini, Stefania; Mammi, Caterina; Infante, Marco; Caprio, Massimiliano
Abstract:
<p>The original book chapter is available at https://www.intechopen.com/</p>
<p>In addition to the well-documented role in the kidney, the mineralocorticoid receptor (MR) has been recently identified in different “non-classical” target tissues, such as the brain, the heart, vasculature, macrophages/monocytes, and adipose tissue. In this context, the MR is involved in adipocyte fundamental processes such as differentiation, autophagy, and adipokine secretion. Excessive activation of the MR contributes to metabolic derangements occurring in mice with obesity and metabolic syndrome. Interestingly, MR pharmacological blockade in murine models of obesity has led to protection from weight gain and adipocyte dysfunctions. Unfortunately, there is still a lack of knowledge on the metabolic effects of MR antagonists, and larger clinical studies are deemed necessary to clarify the metabolic role of MR blockade in humans. This review discusses the role of MR in adipose tis...
https://epubs.rcsi.ie/molmedart/51
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Investigating the Role of Von Willebrand Factor in Regulating Macrophage Biology and Innate Immunity
(2019)
DRAKEFORD, CLIVE
Investigating the Role of Von Willebrand Factor in Regulating Macrophage Biology and Innate Immunity
(2019)
DRAKEFORD, CLIVE
Abstract:
The plasma multimeric glycoprotein von Willebrand factor (VWF) plays a critical role in primary haemostasis by tethering platelets to exposed collagen at sites of vascular injury. Recent studies have suggested that VWF may play an important role in regulating inflammatory responses. In particular, data from clinical trials have demonstrated that patients with reduced plasma VWF levels are significantly protected against ischemic heart disease and stroke. In addition, studies performed in a number of animal inflammation models (including, sepsis, dermatitis, stroke and malaria) have reported a pathogenic role for VWF. Critically however, the biological mechanisms through which VWF exerts its immuno-modulatory effects remain poorly understood. Interestingly, recent studies have shown that VWF can bind to macrophages. Furthermore, a number of specific macrophage receptors have been implicated in regulating the binding of VWF, including the low density lipoprotein receptor-related prote...
http://hdl.handle.net/2262/90724
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Solving the chemical master equation for monomolecular reaction systems analytically
(2007)
Jahnke, Tobias; Huisinga, Wilhelm
Solving the chemical master equation for monomolecular reaction systems analytically
(2007)
Jahnke, Tobias; Huisinga, Wilhelm
Abstract:
The stochastic dynamics of a well-stirred mixture of molecular species interacting through different biochemical reactions can be accurately modelled by the chemical master equation (CME). Research in the biology and scientific computing community has concentrated mostly on the development of numerical techniques to approximate the solution of the CME via many realizations of the associated Markov jump process. The domain of exact and/or efficient methods for directly solving the CME is still widely open, which is due to its large dimension that grows exponentially with the number of molecular species involved. In this article, we present an exact solution formula of the CME for arbitrary initial conditions in the case where the underlying system is governed by monomolecular reactions. The solution can be expressed in terms of the convolution of multinomial and product Poisson distributions with time-dependent parameters evolving according to the traditional reaction-rate equations....
http://mural.maynoothuniversity.ie/1729/
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Determining the expected variability of immune responses using the Cyton Model
(2008)
Subramanian, Vijay G.; Duffy, Ken R.; Turner, Marian L.; Hodgkin, Philip D.
Determining the expected variability of immune responses using the Cyton Model
(2008)
Subramanian, Vijay G.; Duffy, Ken R.; Turner, Marian L.; Hodgkin, Philip D.
Abstract:
During an adaptive immune response, lymphocytes proliferate for ve to twenty cell divisions, then stop and die over a period of weeks. The cyton model for regulation of lymphocyte proliferation and survival was introduced by Hawkins et al. [17] to provide a framework for understanding this response and its regulation. The model assumes stochastic values for division and survival times for each cell in a responding population. Experimental evidence indicates that the choice of times is drawn from a skewed distribution such as the lognormal, with the fate of individual cells being potentially highly variable. For this reason we calculate the higher moments of the model so that the expected variability can be determined. To do this we formulate a new analytic framework for the cyton model by introducing a generalization to the Bellman-Harris branching process.
http://mural.maynoothuniversity.ie/1645/
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On the impact of correlation between collaterally consanguineous cells on lymphocyte population dynamics
(2009)
Duffy, Ken R.; Subramanian, Vijay G.
On the impact of correlation between collaterally consanguineous cells on lymphocyte population dynamics
(2009)
Duffy, Ken R.; Subramanian, Vijay G.
Abstract:
During an adaptive immune response, lymphocytes proliferate for five to twenty five cell divisions, then stop and die over a period of weeks. Based on extensive flow cytometry data, Hawkins et al. (PNAS, 2007, 104, 5032{5037) introduced a cell-level stochastic model of lymphocyte population dynamics, called the Cyton Model, that accurately captures mean lymphocyte population size as a function of time. In Subramanian et al. (J. Math. Biol., 2008, 56:6, 861{892), we performed a branching process analysis of the Cyton Model and deduced from parameterizations for in vitro and in vivo data that the immune response is predictable despite each cell's fate being highly variable. One drawback of flow cytometry data is that individual cells cannot be tracked, so that it is not possible to investigate dependencies in the fate of cells within family trees. In the absence of this information, while the Cyton Model abandons one of the usual assumptions of branching processes (the independe...
http://mural.maynoothuniversity.ie/1650/
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Investigating the Relationship between Topology and Evolution in a Dynamic Nematode Odor Genetic Network
(2012)
Fitzpatrick, David A.; O'Halloran, Damien M.
Investigating the Relationship between Topology and Evolution in a Dynamic Nematode Odor Genetic Network
(2012)
Fitzpatrick, David A.; O'Halloran, Damien M.
Abstract:
The relationship between biological network architectures and evolution is unclear. Within the phylum nematoda olfaction represents a critical survival tool. For nematodes, olfaction contributes to multiple processes including the finding of food, hosts, and reproductive partners, making developmental decisions, and evading predators. Here we examine a dynamic nematode odor genetic network to investigate how divergence, diversity, and contribution are shaped by network topology. Our findings describe connectivity frameworks and characteristics that correlate with molecular evolution and contribution across the olfactory network. Our data helps guide the development of a robust evolutionary description of the nematode odor network that may eventually aid in the prediction of interactive and functional qualities of novel nodes.
http://mural.maynoothuniversity.ie/3974/
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Multiple lineage specific expansions within the guanylyl cyclase gene family
(2006)
Fitzpatrick, David A.; O'Halloran, Damien M.; Burnell, Ann
Multiple lineage specific expansions within the guanylyl cyclase gene family
(2006)
Fitzpatrick, David A.; O'Halloran, Damien M.; Burnell, Ann
Abstract:
Background: Guanylyl cyclases (GCs) are responsible for the production of the secondary messenger cyclic guanosine monophosphate, which plays important roles in a variety of physiological responses such as vision, olfaction, muscle contraction, homeostatic regulation, cardiovascular and nervous function. There are two types of GCs in animals, soluble (sGCs) which are found ubiquitously in cell cytoplasm, and receptor (rGC) forms which span cell membranes. The complete genomes of several vertebrate and invertebrate species are now available. These data provide a platform to investigate the evolution of GCs across a diverse range of animal phyla. Results: In this analysis we located GC genes from a broad spectrum of vertebrate and invertebrate animals and reconstructed molecular phylogenies for both sGC and rGC proteins. The most notable features of the resulting phylogenies are the number of lineage specific rGC and sGC expansions that have occurred during metazoan evolution. Among t...
http://mural.maynoothuniversity.ie/1465/
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A fungal phylogeny based on 42 complete genomes derived from supertree and combined gene analysis
(2006)
Fitzpatrick, David A.; Logue, Mary E.; Stajich, Jason E. ; Butler, Geraldine
A fungal phylogeny based on 42 complete genomes derived from supertree and combined gene analysis
(2006)
Fitzpatrick, David A.; Logue, Mary E.; Stajich, Jason E. ; Butler, Geraldine
Abstract:
Background To date, most fungal phylogenies have been derived from single gene comparisons, or from concatenated alignments of a small number of genes. The increase in fungal genome sequencing presents an opportunity to reconstruct evolutionary events using entire genomes. As a tool for future comparative, phylogenomic and phylogenetic studies, we used both supertrees and concatenated alignments to infer relationships between 42 species of fungi for which complete genome sequences are available. Results A dataset of 345,829 genes was extracted from 42 publicly available fungal genomes. Supertree methods were employed to derive phylogenies from 4,805 single gene families. We found that the average consensus supertree method may suffer from long-branch attraction artifacts, while matrix representation with parsimony (MRP) appears to be immune from these. A genome phylogeny was also reconstructed from a concatenated alignment of 153 universally distributed orthologs. Our MRP supertree ...
http://mural.maynoothuniversity.ie/1464/
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Evidence of recent interkingdom horizontal gene transfer between bacteria and Candida parapsilosis
(2008)
Fitzpatrick, David A.; Logue, Mary E.; Butler, Geraldine
Evidence of recent interkingdom horizontal gene transfer between bacteria and Candida parapsilosis
(2008)
Fitzpatrick, David A.; Logue, Mary E.; Butler, Geraldine
Abstract:
Background: To date very few incidences of interdomain gene transfer into fungi have been identified. Here, we used the emerging genome sequences of Candida albicans WO-1, Candida tropicalis, Candida parapsilosis, Clavispora lusitaniae, Pichia guilliermondii, and Lodderomyces elongisporus to identify recent interdomain HGT events. We refer to these as CTG species because they translate the CTG codon as serine rather than leucine, and share a recent common ancestor. Results: Phylogenetic and syntenic information infer that two C. parapsilosis genes originate from bacterial sources. One encodes a putative proline racemase (PR). Phylogenetic analysis also infers that there were independent transfers of bacterial PR enzymes into members of the Pezizomycotina, and protists. The second HGT gene in C. parapsilosis belongs to the phenazine F (PhzF) superfamily. Most CTG species also contain a fungal PhzF homolog. Our phylogeny suggests that the CTG homolog originated from an ancient HGT eve...
http://mural.maynoothuniversity.ie/1463/
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Parasitoids, predators, nematodes and pathogens associated with bark weevil pests in Europe
(2004)
Kenis, M.; Wegensteiner, R.; Griffin, Christine
Parasitoids, predators, nematodes and pathogens associated with bark weevil pests in Europe
(2004)
Kenis, M.; Wegensteiner, R.; Griffin, Christine
Abstract:
Among the main bark weevil pests in Europe, Hylobius abietis L. and Pissodes spp. have the subject of several major studies regarding the biology, impact and use of their natural enemies. In particular, parasitoids and namatodes of H. abietis, and parasitoids of pine and fir Pissodes spp. have been extensively studied. In contrast, very little has been done on Cryptorrhynchus lapathi L., and nothing on Hylobius pinastri (Gyllenhal), or on Otiorrhynchus spp. in the forest environment, probably relflecting their lower importance in forest protection.
http://mural.maynoothuniversity.ie/316/
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Cathepsin L1, the Major Protease Involved in Liver Fluke (Fasciola hepatica) Virulence
(2004)
Collins, Peter R.; Stack, Colin M.; O'Neill, Sandra M.; Doyle, Sean; Ryan, Thecla;...
Cathepsin L1, the Major Protease Involved in Liver Fluke (Fasciola hepatica) Virulence
(2004)
Collins, Peter R.; Stack, Colin M.; O'Neill, Sandra M.; Doyle, Sean; Ryan, Thecla; Brennan, Gerard; Mousley, Angela; Stewart, Michael; Maule, Aaron G.; Dalton, John P.; Donnelly, Sheila
Abstract:
The secretion and activation of the major cathepsin L1 cysteine protease involved in the virulence of the helminth pathogen Fasciola hepatica was investigated. Only the fully processed and active mature enzyme can be detected in medium in which adult F. hepatica are cultured. However, immunocytochemical studies revealed that the inactive procathepsin L1 is packaged in secretory vesicles of epithelial cells that line the parasite gut. These observations suggest that processing and activation of procathepsin L1 occurs following secretion from these cells into the acidic gut lumen. Expression of the 37-kDa procathepsin L1 in Pichia pastoris showed that an intermolecular processing event within a conserved GXNXFXD motif in the propeptide generates an active 30-kDa intermediate form. Further activation of the enzyme was initiated by decreasing the pH to 5.0 and involved the progressive processing of the 37 and 30- kDa forms to other intermediates and finally to a fully mature 24.5 kDa ca...
http://mural.maynoothuniversity.ie/323/
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Propagation of Saccharomyces cerevisiae [PSI] Prion Is Impaired by Factors That Regulate Hsp70 Substrate Binding
(2004)
Jones, Gary; Song, Youtao; Chung, Seyung; Masison, Daniel C.
Propagation of Saccharomyces cerevisiae [PSI] Prion Is Impaired by Factors That Regulate Hsp70 Substrate Binding
(2004)
Jones, Gary; Song, Youtao; Chung, Seyung; Masison, Daniel C.
Abstract:
The Saccharomyces cerevisiae [PSI] prion is believed to be a self-propagating cytoplasmic amyloid. Earlier characterization of HSP70 (SSA1) mutations suggested that [PSI] propagation is impaired by alterations that enhance Ssa1pâs substrate binding. This impairment is overcome by second-site mutations in Ssa1pâs conserved C-terminal motif (GPTVEEVD), which mediates interactions with tetratricopeptide repeat (TPR) cochaperones. Sti1p, a TPR cochaperone homolog of mammalian Hop1 (Hsp70/90 organizing protein), activates Ssa1p ATPase, which promotes substrate binding by Ssa1p. Here we find that in SSA1-21 cells depletion of Sti1p improved [PSI] propagation, while excess Sti1p weakened it. In contrast, depletion of Fes1p, a nucleotide exchange factor for Ssa1p that facilitates substrate release, weakened [PSI] propagation, while overproducing Fes1p improved it. Therefore, alterations of Hsp70 cochaperones that promote or prolong Hsp70 substrate binding impair [PSI] propagation. We al...
http://mural.maynoothuniversity.ie/324/
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The sympathetic nervous system's role in regulating blood pressure variability.
(2001)
Malpas, Simon C.; Leonard, Bridget L.; Guild, Sarah-Jane; Ringwood, John; Navakatikyan,...
The sympathetic nervous system's role in regulating blood pressure variability.
(2001)
Malpas, Simon C.; Leonard, Bridget L.; Guild, Sarah-Jane; Ringwood, John; Navakatikyan, Michael; Austin, Paul C.; Head, Geoffrey A.; Burgess, Don E.
Abstract:
This article focuses on how sympathetic nerve activity (SNA) contributes to the variability seen in blood pressure. Specifically, it examines the following questions: why do oscillations occur at certain frequencies, why do only certain frequencies of oscillations in SNA induce oscillations in the vasculature, and what may be the functional purpose of these oscillations.
http://mural.maynoothuniversity.ie/1909/
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Recurring cluster and operon assembly for Phenylacetate degradation genes
(2009)
Martin, Fergal J.; McInerney, James O.
Recurring cluster and operon assembly for Phenylacetate degradation genes
(2009)
Martin, Fergal J.; McInerney, James O.
Abstract:
Background: A large number of theories have been advanced to explain why genes involved in the same biochemical processes are often co-located in genomes. Most of these theories have been dismissed because empirical data do not match the expectations of the models. In this work we test the hypothesis that cluster formation is most likely due to a selective pressure to gradually colocalise protein products and that operon formation is not an inevitable conclusion of the process. Results: We have selected an exemplar well-characterised biochemical pathway, the phenylacetate degradation pathway, and we show that its complex history is only compatible with a model where a selective advantage accrues from moving genes closer together. This selective pressure is likely to be reasonably weak and only twice in our dataset of 102 genomes do we see independent formation of a complete cluster containing all the catabolic genes in the pathway. Additionally, de novo clustering of genes clearly ...
http://mural.maynoothuniversity.ie/1901/
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