Littérature scientifique sur le sujet « Iron pathways »

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Articles de revues sur le sujet "Iron pathways"

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Conrad, Marcel E., Jay N. Umbreit, Elizabeth G. Moore, Lucille N. Hainsworth, Michael Porubcin, Marcia J. Simovich, Marian T. Nakada, Kevin Dolan et Michael D. Garrick. « Separate pathways for cellular uptake of ferric and ferrous iron ». American Journal of Physiology-Gastrointestinal and Liver Physiology 279, no 4 (1 octobre 2000) : G767—G774. http://dx.doi.org/10.1152/ajpgi.2000.279.4.g767.

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Separate pathways for transport of nontransferrin ferric and ferrous iron into tissue cultured cells were demonstrated. Neither the ferric nor ferrous pathway was shared with either zinc or copper. Manganese shared the ferrous pathway but had no effect on cellular uptake of ferric iron. We postulate that ferric iron was transported into cells via β3-integrin and mobilferrin (IMP), whereas ferrous iron uptake was facilitated by divalent metal transporter-1 (DMT-1; Nramp-2). These conclusions were documented by competitive inhibition studies, utilization of a β3-integrin antibody that blocked uptake of ferric but not ferrous iron, development of an anti-DMT-1 antibody that blocked ferrous iron and manganese uptake but not ferric iron, transfection of DMT-1 DNA into tissue culture cells that showed enhanced uptake of ferrous iron and manganese but neither ferric iron nor zinc, hepatic metal concentrations in mk mice showing decreased iron and manganese but not zinc or copper, and data showing that the addition of reducing agents to tissue culture media altered iron binding to proteins of the IMP and DMT-1 pathways. Although these experiments show ferric and ferrous iron can enter cells via different pathways, they do not indicate which pathway is dominant in humans.
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Conrad, Marcel E., et Jay N. Umbreit. « Pathways of Iron Absorption ». Blood Cells, Molecules, and Diseases 29, no 3 (novembre 2002) : 336–55. http://dx.doi.org/10.1006/bcmd.2002.0564.

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Miethke, Marcus, et Mohamed A. Marahiel. « Siderophore-Based Iron Acquisition and Pathogen Control ». Microbiology and Molecular Biology Reviews 71, no 3 (septembre 2007) : 413–51. http://dx.doi.org/10.1128/mmbr.00012-07.

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SUMMARY High-affinity iron acquisition is mediated by siderophore-dependent pathways in the majority of pathogenic and nonpathogenic bacteria and fungi. Considerable progress has been made in characterizing and understanding mechanisms of siderophore synthesis, secretion, iron scavenging, and siderophore-delivered iron uptake and its release. The regulation of siderophore pathways reveals multilayer networks at the transcriptional and posttranscriptional levels. Due to the key role of many siderophores during virulence, coevolution led to sophisticated strategies of siderophore neutralization by mammals and (re)utilization by bacterial pathogens. Surprisingly, hosts also developed essential siderophore-based iron delivery and cell conversion pathways, which are of interest for diagnostic and therapeutic studies. In the last decades, natural and synthetic compounds have gained attention as potential therapeutics for iron-dependent treatment of infections and further diseases. Promising results for pathogen inhibition were obtained with various siderophore-antibiotic conjugates acting as “Trojan horse” toxins and siderophore pathway inhibitors. In this article, general aspects of siderophore-mediated iron acquisition, recent findings regarding iron-related pathogen-host interactions, and current strategies for iron-dependent pathogen control will be reviewed. Further concepts including the inhibition of novel siderophore pathway targets are discussed.
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Conrad, Marcel E., et Jay N. Umbreit. « Iron absorption : Relative importance of iron transport pathways ». American Journal of Hematology 67, no 3 (2001) : 215. http://dx.doi.org/10.1002/ajh.1114.

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Shakoury-Elizeh, Minoo, John Tiedeman, Jared Rashford, Tracey Ferea, Janos Demeter, Emily Garcia, Ronda Rolfes, Patrick O. Brown, David Botstein et Caroline C. Philpott. « Transcriptional Remodeling in Response to Iron Deprivation inSaccharomyces cerevisiae ». Molecular Biology of the Cell 15, no 3 (mars 2004) : 1233–43. http://dx.doi.org/10.1091/mbc.e03-09-0642.

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The budding yeast Saccharomyces cerevisiae responds to depletion of iron in the environment by activating Aft1p, the major iron-dependent transcription factor, and by transcribing systems involved in the uptake of iron. Here, we have studied the transcriptional response to iron deprivation and have identified new Aft1p target genes. We find that other metabolic pathways are regulated by iron: biotin uptake and biosynthesis, nitrogen assimilation, and purine biosynthesis. Two enzymes active in these pathways, biotin synthase and glutamate synthase, require an iron-sulfur cluster for activity. Iron deprivation activates transcription of the biotin importer and simultaneously represses transcription of the entire biotin biosynthetic pathway. Multiple genes involved in nitrogen assimilation and amino acid metabolism are induced by iron deprivation, whereas glutamate synthase, a key enzyme in nitrogen assimilation, is repressed. A CGG palindrome within the promoter of glutamate synthase confers iron-regulated expression, suggesting control by a transcription factor of the binuclear zinc cluster family. We provide evidence that yeast subjected to iron deprivation undergo a transcriptional remodeling, resulting in a shift from iron-dependent to parallel, but iron-independent, metabolic pathways.
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Perraud, Quentin, Paola Cantero, Béatrice Roche, Véronique Gasser, Vincent P. Normant, Lauriane Kuhn, Philippe Hammann, Gaëtan L. A. Mislin, Laurence Ehret-Sabatier et Isabelle J. Schalk. « Phenotypic Adaption of Pseudomonas aeruginosa by Hacking Siderophores Produced by Other Microorganisms ». Molecular & ; Cellular Proteomics 19, no 4 (5 février 2020) : 589–607. http://dx.doi.org/10.1074/mcp.ra119.001829.

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Bacteria secrete siderophores to access iron, a key nutrient poorly bioavailable and the source of strong competition between microorganisms in most biotopes. Many bacteria also use siderophores produced by other microorganisms (exosiderophores) in a piracy strategy. Pseudomonas aeruginosa, an opportunistic pathogen, produces two siderophores, pyoverdine and pyochelin, and is also able to use a panel of exosiderophores. We first investigated expression of the various iron-uptake pathways of P. aeruginosa in three different growth media using proteomic and RT-qPCR approaches and observed three different phenotypic patterns, indicating complex phenotypic plasticity in the expression of the various iron-uptake pathways. We then investigated the phenotypic plasticity of iron-uptake pathway expression in the presence of various exosiderophores (present individually or as a mixture) under planktonic growth conditions, as well as in an epithelial cell infection assay. In all growth conditions tested, catechol-type exosiderophores were clearly more efficient in inducing the expression of their corresponding transporters than the others, showing that bacteria opt for the use of catechol siderophores to access iron when they are present in the environment. In parallel, expression of the proteins of the pyochelin pathway was significantly repressed under most conditions tested, as well as that of proteins of the pyoverdine pathway, but to a lesser extent. There was no effect on the expression of the heme and ferrous uptake pathways. Overall, these data provide precise insights on how P. aeruginosa adjusts the expression of its various iron-uptake pathways (phenotypic plasticity and switching) to match varying levels of iron and competition.
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Spencer, Michelle J. S., Andrew Hung, Ian K. Snook et Irene Yarovsky. « Iron Surfaces : Pathways to Interfaces ». Surface Review and Letters 10, no 02n03 (avril 2003) : 169–74. http://dx.doi.org/10.1142/s0218625x03005025.

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We have used density functional theory to examine the effects of avalanche in adhesion between Fe(100) surfaces, in registry and out of registry. When the central layers of the two surfaces are constrained the surface layers are attracted towards each other, forming a strained crystal region at intermediate interfacial separations. When the constraints in the z-direction are lifted, the surfaces avalanche together. In addition, when the surfaces are allowed to move sideways, we find that an interface initially out of registry will tend to avalanche towards an interface that is in registry.
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Theil, Elizabeth C. « Mining ferritin iron : 2 pathways ». Blood 114, no 20 (12 novembre 2009) : 4325–26. http://dx.doi.org/10.1182/blood-2009-08-239913.

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Chen, Jen-Chih, Scott I. Hsieh, Janette Kropat et Sabeeha S. Merchant. « A Ferroxidase Encoded by FOX1 Contributes to Iron Assimilation under Conditions of Poor Iron Nutrition in Chlamydomonas ». Eukaryotic Cell 7, no 3 (1 février 2008) : 541–45. http://dx.doi.org/10.1128/ec.00463-07.

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ABSTRACT When the abundance of the FOX1 gene product is reduced, Chlamydomonas cells grow poorly in iron-deficient medium, but not in iron-replete medium, suggesting that FOX1-dependent iron uptake is a high-affinity pathway. Alternative pathways for iron assimilation, such as those involving ZIP family transporters IRT1 and IRT2, may be operational.
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Mercier, Alexandre, et Simon Labbé. « Iron-Dependent Remodeling of Fungal Metabolic Pathways Associated with Ferrichrome Biosynthesis ». Applied and Environmental Microbiology 76, no 12 (30 avril 2010) : 3806–17. http://dx.doi.org/10.1128/aem.00659-10.

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ABSTRACT The fission yeast Schizosaccharomyces pombe excretes and accumulates the hydroxamate-type siderophore ferrichrome. The sib1 + and sib2 + genes encode, respectively, a siderophore synthetase and an l-ornithine N5-oxygenase that participate in ferrichrome biosynthesis. In the present report, we demonstrate that sib1 + and sib2 + are repressed by the GATA-type transcriptional repressor Fep1 in response to high levels of iron. We further found that the loss of Fep1 results in increased ferrichrome production. We showed that a sib1Δ sib2Δ mutant strain exhibits a severe growth defect on iron-poor media. We determined that two metabolic pathways are involved in biosynthesis of ornithine, an obligatory precursor of ferrichrome. Ornithine is produced by hydrolysis of arginine by the Car1 and Car3 proteins. Although car3 + was constitutively expressed, car1 + transcription levels were repressed upon exposure to iron, with a concomitant decrease of Car1 arginase activity. Ornithine is also generated by transformation of glutamate, which itself is produced by two separate biosynthetic pathways which are transcriptionally regulated by iron in an opposite fashion. In one pathway, the glutamate dehydrogenase Gdh1, which produces glutamate from 2-ketoglutarate, was repressed under iron-replete conditions in a Fep1-dependent manner. The other pathway involves two coupled enzymes, glutamine synthetase Gln1 and Fe-S cluster-containing glutamate synthase Glt1, which were both repressed under iron-limiting conditions but were expressed under iron-replete conditions. Collectively, these results indicate that under conditions of iron deprivation, yeast remodels metabolic pathways linked to ferrichrome synthesis in order to limit iron utilization without compromising siderophore production and its ability to sequester iron from the environment.
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Thèses sur le sujet "Iron pathways"

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Mettrick, Karla Adelle, et n/a. « Iron signalling pathways of Pseudomonas aeruginosa ». University of Otago. Department of Biochemistry, 2008. http://adt.otago.ac.nz./public/adt-NZDU20081128.143145.

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The pathogenic bacterium Pseudomonas aeruginosa uses a variety of highly efficient chelating compounds (siderophores) to acquire sufficient iron for growth and virulence. These siderophores can either be endogenous or acquired from exogenous sources such as other bacteria or fungi. The transport of the endogenous siderophore pyoverdine activates a signal-transduction pathway that increases the synthesis of both the ferripyoverdine receptor protein (FpvA) and pyoverdine itself. Signal-transduction systems similar to this have three specific proteins involved: a receptor protein specific for one siderophore in the outer membrane, an anti-sigma factor in the cytoplasmic membrane and a sigma factor that activates gene expression in the cytoplasm. The aim of the research presented in this thesis was to study the roles of the proteins in three different iron uptake and signalling pathways of P. aeruginosa. The substrates for each receptor protein were confirmed and the roles of each protein in the pathways were compared to the P. aeruginosa pyoverdine signalling pathway. The pyoverdine, desferrioxamine and ferrichrome transport pathways were studied to find whether interactions occur between them and if so, the mechanism(s) for that interaction. Furthermore, a technique for analysing gene expression of P. aeruginosa in sputum from the cystic fibrosis (CF) lung was developed. This technique was subsequently used to study the levels of iron responsive gene expression. The receptor, sigma factor and anti-sigma factors were all found to have a role in the siderophore-induced expression of their own signalling pathway. The experimental data provide evidence of similarities in the roles of the sigma and receptor proteins within each pathway but different roles for the anti-sigma factors. In the absence of the cognate sigma factor or anti-sigma factor the expression of the desferrioxamine and ferrichrome receptors could not be upregulated. Without its cognate sigma factor fpvA could no longer be upregulated in the presence of pyoverdine. However, unlike the other systems, in the absence of the cognate anti-sigma factor, expression of fpvA was always observed. This is consistent with the anti-sigma factors being required for the activity of the cognate sigma factor in the ferrichrome and desferrioxamine signalling pathways but not the pyoverdine signalling pathway. The siderophore signalling pathways were found to be upregulated in the presence of multiple siderophores, but generally to a lesser extent than if only one siderophore was available. This suggests that in the presence of multiple siderophores, P. aeruginosa uses all available iron chelators. The study of the role of the receptor, sigma factor and anti-sigma factor into these effects indicate sigma factor competition for RNA polymerase has a major role in the effects of multiple siderophores on pathways upregulation. The gene expression studies of P. aeruginosa in sputum from the lungs of CF patients provided support for the hypothesis that the bacteria were growing in an environment where iron levels were sufficient for bacterial growth, but not storage of iron. The expression of the sigma factor gene pvdS that is required for pyoverdine synthesis was studied because expression of this gene is a sensitive reporter of intracellular iron levels. It was found to be downregulated in bacteria in sputum compared to laboratory grown bacteria. This result suggests the bacteria are inhabiting a more iron-replete environment within the lung. This finding advances our understanding of the CF lung environment and the impact it has on P. aeruginosa infection. This knowledge has medical implications for the development of novel therapies to combat P. aeruginosa infection.
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Gomez, Perez Laura. « Alternative electron transfer pathways in iron-metabolising bacteria ». Thesis, University of East Anglia, 2018. https://ueaeprints.uea.ac.uk/69911/.

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Ferric iron (Fe3+) can be used as a terminal electron acceptor by iron-reducing microorganisms to facilitate cellular respiration under anoxic conditions. In contrast, ferrous iron (Fe2+) is used as an electron donor by iron-oxidising microorganisms. The presence of dissimilatory pathways in iron metabolisers maintain bioavailable iron in the environment for other organisms. Redox reactions between gram-negative bacteria and iron usually occur through an extracellular electron transport (EET) pathway that allows electrons to cross from the inner membrane to the extracellular environment or vice versa. The study of the redox pathway has been thoroughly studied in the iron reducer Shewanella oneidensis, however, there is little information about the metabolic pathways used by other iron metabolisers. In this thesis, the environmental isolates Acinetobacter and Citrobacter have been described as novel iron reducing bacteria by using a combination of techniques including ferrozine assays, cytochrome identification methods and transcriptomic analysis. Results in this thesis suggest that Acinetobacter (previously described as a strict aerobic microorganism) in fact is capable of respiring using iron when oxygen is not available. In contrast, Citrobacter's iron reduction pathway seems to involve fermentative processes. These results point out that extracellular electron transport is not the only mechanism in dissimilatory iron metabolism. Moreover, these results suggest that anaerobic environments could be a reservoir for pathogenic strains of Acinetobacter, as it has been shown that this species do not require oxygen to survive. In addition to the study of new iron reducers, an overexpression system has been developed to study proteins involved in metal oxidation pathways without the need of culturing the notoriously slow-growing iron oxidising bacteria. The genes cyc2 and cyc2PV-1, which encode outer membranes cytochromes from Acidithiobacillus ferrooxidans and Mariprofundus ferrooxydans respectively, have been transformed into the iron reducer Shewanella oneidensis for protein expression optimization. The optimization of this process offers great possibility for the future study and applications of metal oxidation pathways.
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Gabrielli, Natalia 1978. « Cross-talk between iron starvation and H202 signaling pathways in Schizosaccharomyces pombe ». Doctoral thesis, Universitat Pompeu Fabra, 2012. http://hdl.handle.net/10803/108037.

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Hydrogen peroxide (H2O2), a reactive oxygen species (ROS), is involved in both oxidative stress and signaling cascades in a dosage dependent manner. Its toxicity is partially explained through reactivity with iron via the Fenton reaction. Iron, indispensible for many cellular processes, is thus tightly regulated to balance between need and toxicity. Using fission yeast as a model system, we explored the relationship between H2O2 and the iron starvation response system, specifically whether cross-talk allowed mutual regulation that could prevent synergistic toxicity of ROS via diminishing iron quantity. We screened around of 2700 haploid Schizosaccharomyces pombe deletion mutants in different oxidative stress agents, identifying new genes amongst which fep1, pcl1 and sib2 are involved in iron homeostasis. H2O2, unexpectedly, triggers transcriptional iron starvation response, including enhanced iron import and decreased iron consumption. Over-expression of several antioxidant proteins, in particular heme-containing catalase, causes strong iron consumption within the cell, triggering the iron starvation pathway accidentally. Furthermore, glutaredoxin Grx4 contains an iron-sulfur cluster (ISC) involved in iron sensing, underpinning regulation of the iron starvation response. Finally, we identify and characterize the frataxin homolog gene in S. pombe, pfh1. Deficiencies in frataxin provoke a neurodegenerative disease called Friedreich ataxia; the function of this protein remains controversial. We create ∆pfh1 strain as a new model system to elucidate the molecular events leading to the disease.
El peróxido de hidrógeno (H2O2) es un agente oxidante que además de participar en cascadas de señalización produce toxicidad por daño oxidativo. Parte de su toxicidad se explica por su reactividad con hierro. Así, las concentraciones de hierro en el interior celular han de estar estrictamente reguladas. Usando la levadura de fisión, Schizosaccharomyces pombe, como un sistema modelo, estudiamos las relaciones entre H2O2 y el sistema de respuesta a déficit de hierro. Genes como fep1, pcl1 y sib2, importantes para mantener su homeostasis, fueron encontrados en un análisis de 2700 mutantes de S. pombe, tras tratamiento con diferentes agentes oxidantes. Inesperadamente encontramos que H2O2 desencadena una respuesta transcripcional de déficit de hierro, incluyendo aumento de su entrada y disminución de su consumo. Ésta es una respuesta accidental debido a la sobreexpresión de proteínas como catalasa, una hemoproteína, consumidoras masivas de hierro. Encontramos además que la glutaredoxina Grx4 contiene un clúster de hierro-azufre implicado en sensar hierro. Finalmente, identificamos, caracterizamos y delecionamos el homólogo de frataxina en S. pombe, pfh1. Deficiencias en frataxina provocan ataxia de Friedreich. Los mecanismos por los cuales se desencadena esta enfermedad están todavía por elucidar, pero S. pombe es un buen sistema modelo para su estudio.
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Birmingham, Ryan W. « TRANSPORT PATHWAYS OF SHELF SOURCE MICRONUTRIENTS TO THE SOUTHERN OCEAN ». Thesis, Georgia Institute of Technology, 2015. http://hdl.handle.net/1853/53728.

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We use a numerical ocean model to evaluate the hypothesis that the continental shelves are significant sources of dissolved iron to the Southern Ocean. We simulate the distribution of passive tracers released from the 18 different continental shelf regions of the extra-tropical southern hemisphere oceans using an offline, eddy-permitting transport model. The circulation fields are taken from the Southern Ocean State Estimate, and we only simulate the transport of inert tracers focusing on the physical transport pathways. The resulting tracer fields are then compared with the remotely sensed ocean color data, revealing a remarkable resemblance between the distributions of shelf-source tracers and the climatological surface chlorophyll-a concentrations. We further analyze the spatial pattern of simulated tracer fields in relation to satellite ocean color data. Dynamic ocean features such as the Southern Ocean fronts and coastal waters are reflected in both the tracer model and the observed biological productivity. Our results support the overall importance of continental shelves as a potential source region for dissolved iron. The relative importance of different shelf regions is found to vary significantly depending on the relevant circulation features.
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Neate, Peter Gregory Nigel. « Pathways to sustainable catalysis : from novel catalysts to mechanistic understanding ». Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/25441.

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Catalysis allows for the controlled formation of new bonds, whilst reducing both time and energy expenditure in the process. Catalysis has traditionally been the realm of precious metals, which have been used to carry out a bewildering array of reactions. However, there is an ever-increasing drive for the development of catalytic methodology employing sustainable and environmentally benign catalysts. Two such candidates are organocatalysis, omitting the need for metals where possible, or the use of iron catalysis. Two key areas to the advancement of the of field catalysis are the identification and development of new catalysts as well as an understanding of the mechanisms of established catalytic processes. Novel catalysts can provide many benefits such as enhanced or even novel reactivity, access to new classes of substrates or simply be more readily accessible compared with previously developed catalysts. To this end, the first example of Lewis-base-catalysis using the recently developed cyclopropenimine motif is reported. This was exploited in the trifluoromethylation of aldehydes and ketones using the Rupert-Prakash reagent (Scheme A-1). Scheme A-1 Cyclopropenimine-catalysed trifluoromethylation of aldehydes and ketones Developing an understanding of catalytic methodologies in the terms of their mechanism and active species is also a key area in catalysis. Insight into these can direct the expansion of these systems in terms of both more effective catalysts and tailoring reaction conditions as examples. The iron-catalysed hydromagnesiation of styrene derivatives was studied in detail. This culminated in a proposed mechanism, involving a novel hydride transfer process (Scheme A-2). Studies were carried out using a combination of kinetic analysis and in situ Mössbauer spectroscopy, as well as successfully isolating and studying the reactivity of a catalytically-relevant, formal iron(0)-species.
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Gonska, Nathalie. « Proton pathways in energy conversion : K-pathway analogs in O2- and NO-reductases ». Doctoral thesis, Stockholms universitet, Institutionen för biokemi och biofysik, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-147267.

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Oxygen and nitric oxide reductases are enzymes found in aerobic and anaerobic respiration, respectively. Both enzyme groups belong to the superfamily of Heme-Copper Oxidases, which is further divided into several subgroups: oxygen-reducing enzymes into A-, B- and C-type and nitric oxide reductases into qNORs and cNORs. Oxygen reducing enzymes use the energy released from oxygen reduction to take up electrons and protons from different sides of the membrane. Additionally, protons are pumped. These processes produce a membrane potential, which is used by the ATP-synthase to produce ATP, the universal energy currency of the cell. Nitric oxide reductases are not known to conserve the energy from nitric oxide reduction, although the reaction is highly exergonic. Here, the detailed mechanism of a B-type oxidase is studied with special interest in an element involved in proton pumping (proton loading site, PLS). The study supports the hypothesis that the PLS is protonated in one and deprotonated in the consecutive step of the oxidative catalytic cycle, and that a proton is pumped during the final oxidation phase. It further strengthens the previous suggestion that the PLS is a cluster instead of a single residue or heme propionate. Additionally, it is proposed that the residue Asp372, which is in vicinity of the heme a3 propionates previously suggested as PLS, is part of this cluster. In another study, we show that the Glu15II at the entry of the proton pathway in the B-type oxidase is the only crucial residue for proton uptake, while Tyr248 is or is close to the internal proton donor responsible for coupling proton pumping to oxygen reduction. The thesis also includes studies on the mechanism and electrogenicity of qNOR. We show that there is a difference in the proton-uptake reaction between qNOR and the non-electrogenic homolog cNOR, hinting at a different reaction mechanism. Further, studies on a qNOR from a different host showed that qNOR is indeed electrogenic. This surprising result opens up new discussions on the evolution of oxygen and nitric oxide reductases, and about how energy conservation can be achieved.

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.

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Kirby, Shane Douglas. « Ferric binding proteins, identification and role in the iron acquisition pathways of the Pasteurellaceae and Neisseriaceae ». Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0008/NQ49508.pdf.

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Diekrup, David. « Depositional Pathways and the Post-Depositional History of the Neoarchean Algoma-Type BIF in Temagami, ON ». Thesis, Université d'Ottawa / University of Ottawa, 2019. http://hdl.handle.net/10393/39875.

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Algoma-type banded iron formation is common in Neoarchean greenstone belts, and many of its distinctive features such as the banding of iron-rich and silica-rich material and deposition in volcanic terranes have been ascribed to their deposition related to volcanic-hydrothermal activity and cyclic variability in depositional pathways. The work presented in this thesis tests these assumptions and presents a model for the deposition and post-depositional processes now represented by the petrography and geochemistry of a 2.73 Ga type-locality of Algoma-type BIF in Temagami, ON. Adsorption of components onto the surface of Fe-oxyhydroxides forming in the anoxic Neoarchean water column is the most likely process capable of transferring silica, as well as trace quantities of transition metals, rare earth elements, Ge, P, U and other components to the sediment. The petrogenesis of the Temagami BIF lithologies suggests ongoing recrystallization processes and volume loss reactions leading to the formation of magnetite layers, while jasper is identified as the most pristine lithology best representative of the initially deposited Fe-oxyhydroxide-silica gel. Recrystallization and volume loss reactions are controlled by the ongoing dewatering during compaction and diagenesis, without the influence of external hydrothermal or metamorphic fluids. When corrected for the volume loss and small amounts of clastic contamination, little residual variability can be observed in the composition of jasper and magnetite layers, indicative of an originally homogenous primary precipitate instead of sorted and layered material deposited on the seafloor. This model is in stark contrast to previous interpretations of seasonal variability in biologic activity, cyclical seasonal or hydrothermal events responsible for primary layering in BIF. Instead, very little direct input of hydrothermal components is recorded in the chemistry of the Temagami BIF, and elements abundant in high-temperature hydrothermal fluids such as sulfur are instead sourced from atmospheric sources and deposited by bacterial pathways. Lack of primary chemical variability and non-hydrothermally sourced components captured in BIF argue against a genetic link to local hydrothermal venting, but rather an open ocean depositional setting. As such, the Temagami BIF does not represent a marker horizon related to local or regional hydrothermal venting and potential formation of associated massive sulfide deposits but reflects processes and the chemistry of the open Neoarchean ocean.
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Parkin, David. « Decomposition pathways of an S-nitroso sugar, S-nitroso dithiols and the reaction of S-nitrosothiols with iron complexes ». Thesis, Durham University, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.251214.

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Ruegg, Evonne Teresa Nicole. « Investigating the porphyrias through analysis of biochemical pathways ». Thesis, University of Canterbury. Biochemistry, 2014. http://hdl.handle.net/10092/10257.

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ABSTRACT The porphyrias are a diverse group of metabolic disorders arising from diminished activity of enzymes in the heme biosynthetic pathway. They can present with acute neurovisceral symptoms, cutaneous symptoms, or both. The complexity of these disorders is demonstrated by the fact that some acute porphyria patients with the underlying genetic defect(s) are latent and asymptomatic while others present with severe symptoms. This indicates that there is at least one other risk factor required in addition to the genetic defect for symptom manifestation. A systematic review of the heme biosynthetic pathway highlighted the involvement of a number of micronutrient cofactors. An exhaustive review of the medical literature uncovered numerous reports of micronutrient deficiencies in the porphyrias as well as successful case reports of treatments with micronutrients. Many micronutrient deficiencies present with symptoms similar to those in porphyria, in particular vitamin B6. It is hypothesized that a vitamin B6 deficiency and related micronutrient deficiencies may play a major role in the pathogenesis of the acute porphyrias. In order to further investigate the porphyrias, a computational model of the heme biosynthetic pathway was developed based on kinetic parameters derived from a careful analysis of the literature. This model demonstrated aspects of normal heme biosynthesis and illustrated some of the disordered biochemistry of acute intermittent porphyria (AIP). The testing of this model highlighted the modifications necessary to develop a more comprehensive model with the potential to investigated hypotheses of the disordered biochemistry of the porphyrias as well as the discovery of new methods of treatment and symptom control. It is concluded that vitamin B6 deficiency might be the risk factor necessary in conjunction with the genetic defect to trigger porphyria symptoms.
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Livres sur le sujet "Iron pathways"

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author, Horak Kathryn E., dir. McCarren Play Center, including the bath house, swimming pool, diving pool, wading pool, filter house, lifeguard house, brick perimeter walls, piers and cast-iron fencing, comfort stations, linking pathways, and the planted median paralleling the western side of the bath house : Lorimer Street between Driggs Avenue and Bayard Street, Borough of Brooklyn. New York, N.Y.] : Landmarks Preservation Commission, 2007.

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author, Presa Donald G., dir. Astoria Park Pool and Play Center, including the bath house, wading pool, diving pool, filter house, bleachers, brick perimeter walls, piers and cast iron fencing, stairways to bath house roof-top observation decks, comfort station, and connecting pathways, 19th Street between 22nd Drive and Hoyt Avenue North, Astoria Park, Borough of Queens : Constructed 1934-36 ; John M. Hatton and others, Architects ; Aymar Embury II, Consulting Architect ; Gilmore D. Clarke and others, Landscape Architects. New York, N.Y.] : Landmarks Preservation Commission, 2006.

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Trocello, Jean-Marc, et France Woimant. Disorders of Copper and Iron Metabolism. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199972135.003.0044.

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Both copper and iron are essential metals that have a critical function in a series of biochemical pathways. This chapter describes the disorders associated with genetic abnormalities in copper and iron metabolic pathways and their manifestations in adult patients. Mutations in the genes of the copper transporting P-type ATPases, ATP7A and ATP7B are associated with Wilson disease, Menkes disease, occipital horn syndrome and ATP7A-related distal motor neuropathy. Neurodegeneration with brain iron accumulation (NBIA) is a group of disorders characterized by excess iron deposition in globus pallidus, substantia nigra pars reticulata, striata and cerebellar dentate nuclei. Several genes associated with NBIA have been identified.
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LaRoche, Cheryl Janifer. Poke Patch, Ohio. University of Illinois Press, 2017. http://dx.doi.org/10.5406/illinois/9780252038044.003.0005.

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This chapter examines the relationship between the Underground Railroad and Poke Patch's free Black community, arguing that routes connecting iron furnace regions surrounding the community reveal an overlooked escape strategy for those fleeing slavery. After providing an overview of Ohio's multiple highly developed routes along the Underground Railroad, the chapter discusses the role of Poke Patch as an Underground Railroad site in the state. It then considers the Black Baptist Church's involvement in the Underground Railroad, along with the AME Church's role in helping escapees fleeing slavery. It also describes several escape routes leading into and out of Poke Patch, including one that converged at Berlin Crossroads, and those running toward Ohio's iron furnaces in Lawrence and Gallia Counties. The chapter explains how routes connecting these iron furnaces served as major pathways to freedom, with free Blacks silently operating in the background.
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LaRoche, Cheryl Janifer. The Geography of Resistance. University of Illinois Press, 2017. http://dx.doi.org/10.5406/illinois/9780252038044.003.0006.

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This chapter examines escape routes, churches, iron forges and furnaces, and waterways that make up the pathways to freedom and “the geography of resistance.” It considers the concept of freedom as a place by exploring the connections between freedom and the landscape, and between Black communities and the Underground Railroad. It discusses the obstacles that captives escaping slavery had to hurdle, such as losing the challenges of the terrain and bad weather, betrayal, physical suffering, and slave catchers. It also looks at houses as artifacts of the Underground Railroad in the landscape, along with the patterns of rural Black settlements and how most free Blacks often found themselves saddled with the least desirable land. It argues that the landscape is an intimate component of the Black experience, providing crucial pathways out of slavery, and that generations of escapees on the Underground Railroad turned to the sheltering anonymity of the land to conceal their journey.
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Accardo, Jennifer. Restless Legs Syndrome and Periodic Limb Movement Disorder. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199937837.003.0172.

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Restless legs syndrome (RLS), also known as Willis Ekbom disease (WED), is a sensory disorder with a circadian component. An irresistible urge to move the legs disrupts sleep onset and maintenance. Periodic limb movements in sleep, semirhythmic in nature, often overlap with RLS, though periodic limb movement disorder can be diagnosed in the absence of RLS’s distinctive sensory symptoms. Disruptions in dopaminergic pathways, iron metabolism, and the opioid system have all been implicated in pathogenesis, and there is a strong genetic component. RLS is common, affecting 5% to 10% of adults. Its best-known treatments are dopamine agonists; however, other treatments are effective.
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Higham, Charles F. W., et Nam C. Kim, dir. The Oxford Handbook of Early Southeast Asia. Oxford University Press, 2022. http://dx.doi.org/10.1093/oxfordhb/9780199355358.001.0001.

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Southeast Asia is one of the most significant regions in the world for tracing human prehistory over a period of 2 million years. Migrations from the African homeland saw settlement by Homo erectus and Homo floresiensis. Anatomically Modern Humans reached Southeast Asia at least 60,000 years ago to establish a hunter-gatherer tradition, adapting as climatic change saw sea levels fluctuate by over 100 meters. From about 2000 BC, settlement was affected by successive innovations that took place to the north and west. The first rice and millet farmers came by riverine and coastal routes to integrate with indigenous hunters. A millennium later, knowledge of bronze casting penetrated along similar pathways. Copper mines were identified, and metals were exchanged over hundreds of kilometers as elites commanded access to this new material. This Bronze Age ended with the rise of a maritime exchange network that circulated new ideas, religions and artifacts with adjacent areas of present-day India and China. Port cities were founded as knowledge of iron forging rapidly spread, as did exotic ornaments fashioned from glass, carnelian, gold, and silver. In the Mekong Delta, these developments led to an early transition into the state known as Funan. However, the transition to early states in inland regions arose as a sharp decline in monsoon rains stimulated an agricultural revolution involving permanent plowed rice fields. These twin developments illuminate how the great early kingdoms of Angkor, Champa, and Central Thailand came to be, a vital stage in understanding the roots of modern states.
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Sewlal, Robin, dir. REFLECTIONS of the SOUTH AFRICAN MEDIA 1994 - 2019. Radiocracy, 2021. http://dx.doi.org/10.51415/dut.3.

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Prior to 1994, the media operated in an environment that can best be described as ‘suppressed’. Diversity of thoughts, views and opinions on media platforms were non-existent as the regime, at the time, ruled with an iron-fist. A variety of print media outlets sought to reflect reality, but it was a steady struggle especially for those with meagre resources, and exacerbated by the constant clampdowns. The state-run broadcaster, if anything, entrenched discriminatory principles and practices. Given our precarious past, the birth of democracy proved to be the perfect panacea for a promising pathway for the media fraternity. Transformation, in more ways than one, permeated the sector. Reflections of the South African Media: 1994-2019 is a compilation by authors who have peculiar insight of and excelled in the different areas of the fast-developing industry in the first 25 years of South Africa’s democracy. And they are no ordinary authors. Every chapter contributed came from women and men who had, through the years, a direct link with ML Sultan Technikon, Technikon Natal, Durban Institute of Technology (DIT) or Durban University of Technology (DUT) * either as a student, lecturer, visiting professor, speaker or associate. Compiling and editing this book has been an incredibly invigorating experience. It was never in doubt whose image will adorn the cover of the book, so it was beautifully uplifting that many authors, not knowing my choice, gave Nelson Mandela due recognition. My brief to the authors was simple: let me have your personal lookback in your own style on the topic that you are most comfortable with. All of them stepped up to the plate, and the vast array of content in the book bares strong testimony. A section titled Journeys in Journalism encapsulates input from alumni of DUT Journalism – they were afforded free reign to trace the territory they traversed. I’m indebted to each and every contributor for generously volunteering their precious time and talent to the book. They were simply magnificent. It has to be said that this publication far exceeded my expectations as it, initially, was a humble idea to celebrate 25 years of the media industry with a handful of contributions. Little did I realise that my desk will be flooded with 40 pieces of excellence and a Foreword penned by the brilliant Jeremy Thompson. My eternal gratitude must also be extended to the small team of assistants for understanding my vision upfront and rallying remarkably throughout. Once you’ve enjoyed the read, I invite you to share Reflections of the South African Media: 1994-2019 with whoever you believe can benefit from its rich and diverse content!
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Chapitres de livres sur le sujet "Iron pathways"

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Smith, Ann. « Iron Salvage Pathways ». Dans Iron Physiology and Pathophysiology in Humans, 141–71. Totowa, NJ : Humana Press, 2011. http://dx.doi.org/10.1007/978-1-60327-485-2_8.

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Vecchi, Chiara, et Antonello Pietrangelo. « Hepcidin and iron ». Dans Signaling Pathways in Liver Diseases, 400–410. Chichester, UK : John Wiley & Sons, Ltd, 2015. http://dx.doi.org/10.1002/9781118663387.ch29.

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Thurston, Tina L. « Bitter Arrows and Generous Gifts : WhatWas a ‘King’ in the European Iron Age ? » Dans Pathways to Power, 193–254. New York, NY : Springer New York, 2010. http://dx.doi.org/10.1007/978-1-4419-6300-0_8.

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Farver, Ole, et Israel Pecht. « Elucidation of Electron- Transfer Pathways in Copper and Iron Proteins by Pulse Radiolysis Experiments ». Dans Progress in Inorganic Chemistry, 1–78. Hoboken, NJ, USA : John Wiley & Sons, Inc., 2008. http://dx.doi.org/10.1002/9780470144428.ch1.

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Garg, Shikha, Andrew L. Rose et T. David Waite. « Pathways Contributing to the Formation and Decay of Ferrous Iron in Sunlit Natural Waters ». Dans ACS Symposium Series, 153–76. Washington, DC : American Chemical Society, 2011. http://dx.doi.org/10.1021/bk-2011-1071.ch008.

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Groves, John T., et Zeev Gross. « On the Mechanism of Epoxidation and Hydroxylation Catalyzed by Iron Porphyrins. Evidence for Non-Intersecting Reaction Pathways ». Dans Bioinorganic Chemistry, 39–47. Dordrecht : Springer Netherlands, 1995. http://dx.doi.org/10.1007/978-94-011-0255-1_4.

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Rebeiz, Constantin A. « The Iron and Magnesium Branches of the Porphyrin Biosynthetic Pathway ». Dans Chlorophyll Biosynthesis and Technological Applications, 183–96. Dordrecht : Springer Netherlands, 2013. http://dx.doi.org/10.1007/978-94-007-7134-5_6.

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Kerr, P., Q. Liu et T. H. Etsell. « Iron Segregation Roasting as a Potential Decarbonization Pathway for Ironmaking ». Dans Proceedings of the 61st Conference of Metallurgists, COM 2022, 207–9. Cham : Springer International Publishing, 2023. http://dx.doi.org/10.1007/978-3-031-17425-4_30.

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Tabatabai, Adnan. « Iran and Saudi Arabia’s Difficult Pathway Toward Reconciliation : A Conversation ». Dans Frontiers in International Relations, 135–44. Cham : Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-55144-5_10.

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Konijn, A. M., E. G. Meyron-Holtz, D. Gelvan et E. Fibach. « Cellular Ferritin Uptake : A Highly Regulated Pathway for Iron Assimilation in Human Erythroid Precursor Cells ». Dans Advances in Experimental Medicine and Biology, 189–97. Boston, MA : Springer US, 1994. http://dx.doi.org/10.1007/978-1-4615-2554-7_21.

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Actes de conférences sur le sujet "Iron pathways"

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Monson, Todd, Tyler Stevens, Charles Pearce, Melinda Hoyt, Erika Vreeland, Robert Delaney, Stanley Atcitty et al. « New pathways to iron nitride soft magnets. » Dans Proposed for presentation at the Magnetism and Magnetic Materials 2020. US DOE, 2020. http://dx.doi.org/10.2172/1830981.

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Faupel, Franziska. « Reconstructing Early Iron Age pathways in the Upper Rhine Valley ». Dans Interdisciplinarité et nouvelles approches dans les recherches sur l'âge du Fer. Interdisciplinarity and New Approaches in the Research of the Iron Age. Brno : Masarykova univerzita, 2017. http://dx.doi.org/10.5817/cz.muni.p210-8822-2017-17.

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Hockmann, Kerstin, Niloofar Karimian, Sara Schlagenhauff, Britta Planer-Friedrich et Edward D. Burton. « Antimony Mobility and Influence on Iron(II)-Catalyzed Ferrihydrite Transformation Pathways ». Dans Goldschmidt2020. Geochemical Society, 2020. http://dx.doi.org/10.46427/gold2020.1042.

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Anfinrud, Philip A., Chui-Hee Han, Tianquan Lian et Robin M. Hochstrasser. « Subpicosecond Infrared Spectroscopy : the Condensed Phase Photochemistry of Iron Carbonyls ». Dans International Conference on Ultrafast Phenomena. Washington, D.C. : Optica Publishing Group, 1990. http://dx.doi.org/10.1364/up.1990.mc17.

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The condensed phase photochemistry of transition metal carbonyls has been investigated by various techniques in recent years. It is anticipated that such studies will contribute to our understanding of coordinatively unsaturated organometallic complexes and their role in homogeneous catalysis. IR characterization of photogenerated intermediates in isolated matrices has helped to identify photochemical reaction pathways, however, the frozen matrix imposes steric restrictions on pathways which may be important in the liquid phase at room or elevated temperatures. Transient IR methods offering microsecond time resolution have made an important leap in characterizing those reactive intermediates whose lifetimes are determined by diffusion limited bimolecular collisions. Characterization of the primary photochemical events and their products, however, requires significantly improved time resolution. Picosecond transient absorption methods which probe the uv/visible absorption spectrum offer the potential to temporally resolve the ultrafast events leading to the primary photoproducts, however the electronic spectrum is quite complex and generally does not contain features which are structure specific. Clearly, ultrafast IR methods can shed much light on the primary events in condensed phase photochemical processes.
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« Comparison of synthetic pathways of iron (III) complexes with macroligands of fulvic acids for correction of iron deficiency anemia ». Dans Seventh International Conference on Humic Innovative Technologies "Humic substances and technologies for resilience" (HIT – 2022). NP CBR "Humus Sapiens", 2022. http://dx.doi.org/10.36291/hit.2022.072.

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Nikas, A., A. Arsenopoulos, H. Doukas et A. Labella Romero. « Prioritisation of risks associated with decarbonisation pathways for the Austrian iron and steel sector using 2-tuple TOPSIS ». Dans 14th International FLINS Conference (FLINS 2020). WORLD SCIENTIFIC, 2020. http://dx.doi.org/10.1142/9789811223334_0093.

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Lim, Manho, Timothy A. Jackson et Philip A. Anfinrud. « Ultrafast Mid-IR Spectroscopy of Carbonmonoxymyoglobin : The Dynamics of Ligand Motion ». Dans International Conference on Ultrafast Phenomena. Washington, D.C. : Optica Publishing Group, 1994. http://dx.doi.org/10.1364/up.1994.fb.4.

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Myoglobin (Mb) is an oxygen-binding protein found in muscle. The active binding site is an iron-II-containing porphyrin (heme) that is located within the hydrophobic interior of the protein. The X-ray structure of Mb reveals a distal cavity large enough to accommodate a ligand the size of O2, but no channel large enough for the ligand to diffuse between the heme pocket and the surrounding solvent. Clearly, structural fluctuations of the protein are required to open channels for ligand transport to and from the binding site. What is the functional role of the heme pocket and the residues that circumscribe it? What pathways exist for ligand transport between the heme pocket and the solvent? On what time scale does the ligand escape into the surrounding solvent? We have sought to answer these questions by probing the time-resolved vibrational spectrum of CO, a ligand similar in size to O2, following photodissociation of MbCO at physiological temperatures. We have developed a femtosecond time-resolved mid-IR spectrometer with the sensitivity required to measure the “free” CO absorbance. Ultrafast diffusion to a “docking” site has been observed, the orientation of the docked CO relative to the plane of the heme has been measured, and the rate of escape from the heme pocket has been determined. Additional studies with mutants of Mb are being conducted to probe the location of the docking site within the heme pocket and the pathways for ligand escape from the heme pocket.
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Greenwood, Michael, Rawan Eid, Nagla Arab, Chamel Khoury et Paul Young. « Expression of human H ferritin prompts the identification of a hitherto elusive yeast orthologue and enables parsing of distinct iron-induced cell death pathways in Saccharomyces cerevisiae ». Dans 1st Electronic Conference on Molecular Science. Basel, Switzerland : MDPI, 2015. http://dx.doi.org/10.3390/ecms-1-b002.

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de Freitas, Larissa A., Aline A. Vanin, Denise N. Hogetop, Marco N. Bochernitsan et Renata Vieira. « Pathways for irony detection in tweets ». Dans SAC 2014 : Symposium on Applied Computing. New York, NY, USA : ACM, 2014. http://dx.doi.org/10.1145/2554850.2555048.

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Barbosa, Fábio C. « Shortline Freight Rail System Review : North American Experiences and Brazilian Perspectives ». Dans 2020 Joint Rail Conference. American Society of Mechanical Engineers, 2020. http://dx.doi.org/10.1115/jrc2020-8034.

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Abstract Shortline industry plays a prominent role in the North American Freight Rail System (mainly United States and Canada), providing a customized freight rail service to the shippers, i.e. the first/last mile rail access for those low dense/light demand markets, outside the Class I’s business model (highly loaded corridors), as well as competition enhancers, through the connection of shippers facilities with more than one Class I railroad. The Short Line’s Rail industry role and its inherent freight rail business model have been strengthened in the years that followed the so called Staggers Act (1980), in the U.S., in which freight rail carriers have focused their efforts on the high density rail markets. Meanwhile, the Shortlines, also known as Class II and Class III freight rail companies, have lead the way in the light density branch lines, providing a customized freight rail service to those shippers located outside the boundary limits of the rail trunk corridors. The importance of Shortline for the U.S. freight rail industry is illustrated by the 603 U.S. shortlines currently operating on 76,000 km (47,500 miles), providing service for one in five (20%) cars moving each year, which accounts for 29% of freight rail production in the country. Furthermore, the recent launch of the controversial Class I Precision Schedule Railroading (PSR) concept, and its inherent asset maximization (mainly associated with disruptive service features — essentially lane and yards closures), has strengthened the strategic importance of Shortlines in the U.S. freight rail scenario, which ultimately requires an improved Class I – Shortline relationship, to guarantee/maintain a connection between shippers (farmers, manufacturers and other industries), and the customers market. Brazil, a continental country located in South America, has a sprawled and low density rail network (28,218 km – 17,636.25 mi). Besides sprawled/low density, the Brazilian rail network is not uniformly demanded, with just 40% of the network with used (demanded) capacities higher than 50%, basically associated with iron ore and agricultural commodities transport (which accounts for almost 80% of the country’s whole freight rail production), while almost 60% of the network remain with very light use (available capacity higher than 80%). This picture shows a great opportunity for the introduction of the Shortline Rail Concept in the Brazilian Freight Rail System, focused on smaller rail operators to provide a customized and accessible freight rail service for shippers located in the influence area of the rail network. To reach this target, Brazil has basically two alternative pathways: i) a structural approach, associated with a complete network restructuration (in a similar way the U.S. Class I railroads have marketed unproductive branches to short line operators) and ii) a regulatory approach, in which the current concession format would be maintained, with the imposition of rail stretches production targets to current rail concessionaires (incumbents), which ultimately could be encouraged to set operational partnerships with the so called Independent Rail Operators (IRO), to comply with those production rail targets. This work is supposed to present an overview, in a review format, of the North American Shortline Freight Rail experience, highlighting its operational regime/requirements, the business model, the tax incentives and the Shortline’s role in the class I PSR scenario. This analysis is, then, followed by an assessment of the perspectives and the inherent pathways for a Shortline Freight Rail Model implementation in Brazil.
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Rapports d'organisations sur le sujet "Iron pathways"

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Scherer, Michelle M., et Kevin M. Rosso. 2015 Progress Report/July 2016 : Iron Oxide Redox Transformation Pathways : The Bulk Electrical Conduction Mechanism. Office of Scientific and Technical Information (OSTI), juillet 2016. http://dx.doi.org/10.2172/1271183.

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Horwitz, Benjamin A., et Barbara Gillian Turgeon. Fungal Iron Acquisition, Oxidative Stress and Virulence in the Cochliobolus-maize Interaction. United States Department of Agriculture, mars 2012. http://dx.doi.org/10.32747/2012.7709885.bard.

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Our project focused on genes for high affinity iron acquisition in Cochliobolus heterostrophus, a necrotrophic pathogen of maize, and their intertwined relationship to oxidative stress status and virulence of the fungus on the host. An intriguing question was why mutants lacking the nonribosomal peptide synthetase (NRPS) gene (NPS6) responsible for synthesis of the extracellular siderophore, coprogen, are sensitive to oxidative stress. Our overall objective was to understand the mechanistic connection between iron stress and oxidative stress as related to virulence of a plant pathogen to its host. The first objective was to examine the interface where small molecule peptide and reactive oxygen species (ROS) mechanisms overlap. The second objective was to determine if the molecular explanation for common function is common signal transduction pathways. These pathways, built around sensor kinases, response regulators, and transcription factors may link sequestering of iron, production of antioxidants, resistance to oxidative stress, and virulence. We tested these hypotheses by genetic manipulation of the pathogen, virulence assays on the host plant, and by following the expression of key fungal genes. An addition to the original program, made in the first year, was to develop, for fungi, a genetically encoded indicator of redox state based on the commercially available Gfp-based probe pHyper, designed for animal cell biology. We implemented several tools including a genetically encoded indicator of redox state, a procedure to grow iron-depleted plants, and constructed a number of new mutants in regulatory genes. Lack of the major Fe acquisition pathways results in an almost completely avirulent phenotype, showing how critical Fe acquisition is for the pathogen to cause disease. Mutants in conserved signaling pathways have normal ability to regulate NPS6 in response to Fe levels, as do mutants in Lae1 and Vel1, two master regulators of gene expression. Vel1 mutants are sensitive to oxidative stress, and the reason may be underexpression of a catalase gene. In nps6 mutants, CAT3 is also underexpressed, perhaps explaining the sensitivity to oxidative stress. We constructed a deletion mutant for the Fe sensor-regulator SreA and found that it is required for down regulation of NPS6 under Fe-replete conditions. Lack of SreA, though, did not make the fungus over-sensitive to ROS, though the mutant had a slow growth rate. This suggests that overproduction of siderophore under Fe-replete conditions is not very damaging. On the other hand, increasing Fe levels protected nps6 mutants from inhibition by ROS, implying that Fe-catalyzed Fenton reactions are not the main factor in its sensitivity to ROS. We have made some progress in understanding why siderophore mutants are sensitive to oxidative stress, and in doing so, defined some novel regulatory relationships. Catalase genes, which are not directly related to siderophore biosynthesis, are underexpressed in nps6 mutants, suggesting that the siderophore product (with or without bound Fe) may act as a signal. Siderophores, therefore, could be a target for intervention in the field, either by supplying an incorrect signal or blocking a signal normally provided during infection. We already know that nps6 mutants cause smaller lesions and have difficulty establishing invasive growth in the host. Lae1 and Vel1 are the first factors shown to regulate both super virulence conferred by T-toxin, and basic pathogenicity, due to unknown factors. The mutants are also altered in oxidative stress responses, key to success in the infection court, asexual and sexual development, essential for fungal dissemination in the field, aerial hyphal growth, and pigment biosynthesis, essential for survival in the field. Mutants in genes encoding NADPH oxidase (Nox) are compromised in development and virulence. Indeed the triple mutant, which should lack all Nox activity, was nearly avirulent. Again, gene expression experiments provided us with initial evidence that superoxide produced by the fungus may be most important as a signal. Blocking oxidant production by the pathogen may be a way to protect the plant host, in interactions with necrotrophs such as C. heterostrophus which seem to thrive in an oxidant environment.
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Horwitz, Benjamin, et Barbara Gillian Turgeon. Secondary Metabolites, Stress, and Signaling : Roles and Regulation of Peptides Produced by Non-ribosomal Peptide Synthetases. United States Department of Agriculture, 2005. http://dx.doi.org/10.32747/2005.7696522.bard.

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Fungal pathogens of plants produce a diverse array of small molecules. Often referred to as secondary metabolites because they were thought to be dispensable for basic functions, they may indeed have central roles as signals for the fungal cell, and in interactions with the host. We have identified more than a dozen genes encoding nonribosomal peptide synthetases (NPS) in Cochliobolusheterostrophus, the agent of southern corn leaf blight. The aim of this project was to identify roles of these genes in stress responses and signaling. The first objective was to test a complete collection of C. heterostrophus nonribosomal peptide synthetase (NRPS)-encoding gene deletion mutant and wildtype (WT) strains for sensitivity to various agents of oxidative (ROS) and nitrosative (RNOS) stress, in vitro. The second objective and next step in this part of the project was to study the relevance of sensitivity to ROS and RNOS in the host pathogen interaction, by measuring the production of ROS and RNOS in planta, when plants are inoculated with wild type and mutant strains. A third objective was to study expression of any genes shown to be involved in sensitivity to ROS or RNOS, in vitro and in planta. Another objective was to determine if any of the genes involved in oxidative or nitrosative stress responses are regulated by components of signal transduction pathways (STP) that we have identified and to determine where mechanisms overlap. Study of the collection of nps mutants identified phenotypes relevant for virulence, development and oxidative stress resistance for two of the genes, NPS2 and NPS6. Mutants in genes related to RNOS stress have no virulence phenotypes, while some of those related to ROS stress have reduced virulence as well as developmental phenotypes, so we focused primarily on ROS stress pathways. Furthermore, the identification of NPS2 and NPS6 as encoding for NRPS responsible for siderophore biosynthesis lent a new focus to the project, regulation by Fe. We have not yet developed good methods to image ROS in planta and work in this direction is continuing. We found that NPS6 expression is repressed by Fe, responding over the physiological Fe concentration range. Studying our collection of mutants, we found that conserved MAPK and G protein signal transduction pathways are dispensable for Fe regulation of NPS6, and initiated work to identify other pathways. The transcription factor SreA is one candidate, and is responsible for part, but not all, of the control of NPS6 expression. The results of this project show that the pathogen contends with oxidative stress through several signaling pathways. Loss of the siderophore produced by Nps6 makes the fungus sensitive to oxidative stress, and decreases virulence, suggesting a central role of the ability to sequester and take up extracellular iron in the host-pathogen interaction. Siderophores, and manipulation of Fe levels, could be targets for new strategies to deal with fungal pathogens of maize and other plants.
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Savaldi-Goldstein, Sigal, et Siobhan M. Brady. Mechanisms underlying root system architecture adaptation to low phosphate environment. United States Department of Agriculture, janvier 2015. http://dx.doi.org/10.32747/2015.7600024.bard.

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In order to advance our understanding towards potential biotechnology improvement of plant performance, we studied root responses to limited P in two different plants, Arabidopsis and tomato. Arabidopsis is among the most studied model plants that allows rapid application of molecular and developmental experiments while tomato is an important crop, with application in agriculture. Using Arabidopsis we found that steroid hormones modulate the extent of root elongation in response to limited P, by controlling the accumulation of iron in the root. We also found that the availability of P and iron control the activity of the steroid hormone in the root. Finally, we revealed the genes involved in this nutrient-hormone interaction. Hence, the ferroxidase LPR1 that promotes iron accumulation in response to low P is repressed by the transcription factor BES1/BZR1. Low P inhibits the steroid hormone pathway by enhancing the accumulation of BKI1. High levels of BKI1 inhibit the activity of the steroid hormone receptor at the cell surface and iron accumulation increases inside the root, resulting in a slow growth. Together, the extent of root elongation depends on interactions between an internal cue (steroid hormone) and cues derived from the availability of P and iron in the environment. Using tomato, we found that the response of two cultivated tomato varieties (M82 and New Yorker) to limited P is distinct from that of the wild species, Solanumpennellii. This is implicated at both the levels of root development and whole plant physiology. Specifically, while the root system architecture of cultivated tomato is modulated by limited P availability, that of the wild type species remained unaffected. The wild species appears to be always behaving as if it is always in phosphate deprived conditions, despite sufficient levels of phosphate. Hyper-accumulation of metals appears to mediate this response. Together, this knowledge will be used to isolate new genes controlling plant adaptation to limited P environment.
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Chen, Yona, Jeffrey Buyer et Yitzhak Hadar. Microbial Activity in the Rhizosphere in Relation to the Iron Nutrition of Plants. United States Department of Agriculture, octobre 1993. http://dx.doi.org/10.32747/1993.7613020.bard.

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Iron is the fourth most abundant element in the soil, but since it forms insoluble hydroxides at neutral and basic pH, it often falls short of meeting the basic requirements of plants and microorganisms. Most aerobic and facultative aerobic microorganisms possess a high-affinity Fe transport system in which siderophores are excreted and the consequent Fe complex is taken up via a cognate specific receptor and a transport pathway. The role of the siderophore in Fe uptake by plants and microorganisms was the focus of this study. In this research Rhizopus arrhizus was found to produce a novel siderophore named Rhizoferrin when grown under Fe deficiency. This compound was purified and its chemical structure was elucidated. Fe-Rhizoferrin was found to alleviate Fe deficiency when applied to several plants grown in nutrient solutions. It was concluded that Fe-Rhizoferrin is the most efficient Fe source for plants when compared with other among microbial siderophores known to date and its activity equals that of the most efficient synthetic commercial iron fertilizer-Fe EDDHA. Siderophores produced by several rhizosphere organisms including Rhizopus Pseudomonas were purified. Monoclonal antibodies were produced and used to develop a method for detection of the siderophores produced by plant-growth-promoting microorganisms in barley rhizosphere. The presence of an Fe-ferrichrome uptake in fluorescent Pseudomonas spp. was demonstrated, and its structural requirements were mapped in P. putida with the help of biomimetic ferrichrome analogs. Using competition experiments, it was shown that FOB, Cop B and FC share at least one common determinant in their uptake pathway. Since FC analogs did not affect FOB or Cop-mediated 55Fe uptake, it could be concluded that these siderophores make use of a different receptor(s) than FC. Therefore, recognition of Cop, FOB and FC proceeds through different receptors having different structural requirements. On the other hand, the phytosiderophores mugineic acid (MA and DMA), were utilized indirectly via ligand exchange by P. putida. Receptors from different biological systems seem to differ in their structural requirements for siderophore recognition and uptake. The design of genus- or species-specific drugs, probes or chemicals, along with an understanding of plant-microbe and microbe-microbe relationships as well as developing methods to detect siderophores using monoclonal antibodies are useful for manipulating the composition of the rhizosphere microbial population for better plant growth, Fe-nutrition and protection from diseases.
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Blumwald, Eduardo, et Avi Sadka. Citric acid metabolism and mobilization in citrus fruit. United States Department of Agriculture, octobre 2007. http://dx.doi.org/10.32747/2007.7587732.bard.

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Accumulation of citric acid is a major determinant of maturity and fruit quality in citrus. Many citrus varieties accumulate citric acid in concentrations that exceed market desires, reducing grower income and consumer satisfaction. Citrate is accumulated in the vacuole of the juice sac cell, a process that requires both metabolic changes and transport across cellular membranes, in particular, the mitochondrial and the vacuolar (tonoplast) membranes. Although the accumulation of citrate in the vacuoles of juice cells has been clearly demonstrated, the mechanisms for vacuolar citrate homeostasis and the components controlling citrate metabolism and transport are still unknown. Previous results in the PIs’ laboratories have indicated that the expression of a large number of a large number of proteins is enhanced during fruit development, and that the regulation of sugar and acid content in fruits is correlated with the differential expression of a large number of proteins that could play significant roles in fruit acid accumulation and/or regulation of acid content. The objectives of this proposal are: i) the characterization of transporters that mediate the transport of citrate and determine their role in uptake/retrieval in juice sac cells; ii) the study of citric acid metabolism, in particular the effect of arsenical compounds affecting citric acid levels and mobilization; and iii) the development of a citrus fruit proteomics platform to identify and characterize key processes associated with fruit development in general and sugar and acid accumulation in particular. The understanding of the cellular processes that determine the citrate content in citrus fruits will contribute to the development of tools aimed at the enhancement of citrus fruit quality. Our efforts resulted in the identification, cloning and characterization of CsCit1 (Citrus sinensis citrate transporter 1) from Navel oranges (Citrus sinesins cv Washington). Higher levels of CsCit1 transcripts were detected at later stages of fruit development that coincided with the decrease in the juice cell citrate concentrations (Shimada et al., 2006). Our functional analysis revealed that CsCit1 mediates the vacuolar efflux of citrate and that the CsCit1 operates as an electroneutral 1CitrateH2-/2H+ symporter. Our results supported the notion that it is the low permeable citrateH2 - the anion that establishes the buffer capacity of the fruit and determines its overall acidity. On the other hand, it is the more permeable form, CitrateH2-, which is being exported into the cytosol during maturation and controls the citrate catabolism in the juice cells. Our Mass-Spectrometry-based proteomics efforts (using MALDI-TOF-TOF and LC2- MS-MS) identified a large number of fruit juice sac cell proteins and established comparisons of protein synthesis patterns during fruit development. So far, we have identified over 1,500 fruit specific proteins that play roles in sugar metabolism, citric acid cycle, signaling, transport, processing, etc., and organized these proteins into 84 known biosynthetic pathways (Katz et al. 2007). This data is now being integrated in a public database and will serve as a valuable tool for the scientific community in general and fruit scientists in particular. Using molecular, biochemical and physiological approaches we have identified factors affecting the activity of aconitase, which catalyze the first step of citrate catabolism (Shlizerman et al., 2007). Iron limitation specifically reduced the activity of the cytosolic, but not the mitochondrial, aconitase, increasing the acid level in the fruit. Citramalate (a natural compound in the juice) also inhibits the activity of aconitase, and it plays a major role in acid accumulation during the first half of fruit development. On the other hand, arsenite induced increased levels of aconitase, decreasing fruit acidity. We have initiated studies aimed at the identification of the citramalate biosynthetic pathway and the role(s) of isopropylmalate synthase in this pathway. These studies, especially those involved aconitase inhibition by citramalate, are aimed at the development of tools to control fruit acidity, particularly in those cases where acid level declines below the desired threshold. Our work has significant implications both scientifically and practically and is directly aimed at the improvement of fruit quality through the improvement of existing pre- and post-harvest fruit treatments.
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Bercovier, Herve, Raul Barletta et Shlomo Sela. Characterization and Immunogenicity of Mycobacterium paratuberculosis Secreted and Cellular Proteins. United States Department of Agriculture, janvier 1996. http://dx.doi.org/10.32747/1996.7573078.bard.

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Our long-term goal is to develop an efficient acellular vaccine against paratuberculosis based on protein antigen(s). A prerequisite to achieve this goal is to analyze and characterize Mycobacterium paratuberculosis (Mpt) secreted and cellular proteins eliciting a protective immune response. In the context of this general objective, we proposed to identify, clone, produce, and characterize: the Mpt 85B antigen and other Mpt immunoreactive secreted proteins, the Mpt L7/L12 ribosomal protein and other immunoreactive cellular proteins, Mpt protein determinants involved in invasion of epithelial cells, and Mpt protein antigens specifically expressed in macrophages. Paratuberculosis is still a very serious problem in Israel and in the USA. In the USA, a recent survey evaluated that 21.6% of the dairy herd were infected with Mpt resulting in 200-250 million dollars in annual losses. Very little is known on the virulence factors and on protective antigens of Mpt. At present, the only means of controlling this disease are culling or vaccination. The current vaccines do not allow a clear differentiation between infected and vaccinated animals. Our long-term goal is to develop an efficient acellular paratuberculosis vaccine based on Mpt protein antigen(s) compatible with diagnostic tests. To achieve this goal it is necessary to analyze and characterize secreted and cellular proteins candidate for such a vaccine. Representative Mpt libraries (shuttle plasmid and phage) were constructed and used to study Mpt genes and gene products described below and will be made available to other research groups. In addition, two approaches were performed which did not yield the expected results. Mav or Mpt DNA genes that confer upon Msg or E. coli the ability to invade and/or survive within HEp-2 cells were not identified. Likewise, we were unable to characterize the 34-39 kDa induced secreted proteins induced by stress factors due to technical difficulties inherent to the complexity of the media needed to support substantial M. pt growth. We identified, isolated, sequenced five Mpt proteins and expressed four of them as recombinant proteins that allowed the study of their immunological properties in sensitized mice. The AphC protein, found to be up regulated by low iron environment, and the SOD protein are both involved in protecting mycobacteria against damage and killing by reactive oxygen (Sod) and nitrogen (AhpC) intermediates, the main bactericidal mechanisms of phagocytic cells. SOD and L7/L12 ribosomal proteins are structural proteins constitutively expressed. 85B and CFP20 are both secreted proteins. SOD, L7/L12, 85B and CFP20 were shown to induce a Th1 response in immunized mice whereas AphC was shown by others to have a similar activity. These proteins did not interfere with the DTH reaction of naturally infected cows. Cellular immunity provides protection in mycobacterial infections, therefore molecules inducing cellular immunity and preferentially a Th1 pathway will be the best candidate for the development of an acellular vaccine. The proteins characterized in this grant that induce a cell-mediated immunity and seem compatible with diagnostic tests, are good candidates for the construction of a future acellular vaccine.
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