المؤلفون: Sumrall, Eric T., Shen, Yang, Keller, Anja P., Rismondo, Jeanine, Pavlou, Maria, Eugster, Marcel R., Boulos, Samy, Disson, Olivier, Thouvenot, Pierre, Kilcher, Samuel, Wollscheid, Bernd, Cabanes, Didier, Lecuit, Marc, Gründling, Angelika, Loessner, Martin J.

المساهمون: Wellcome Trust, Medical Research Council (MRC), Institute of Food, Nutrition and Health [Zurich, Suisse] (IFNH), Department of Health Sciences and Technology [ETH Zürich] (D-HEST), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Section of Microbiology [Londres, Royaume-Uni], Medical Research Council Centre for Molecular Bacteriology and Infection [Londres, Royaume-Uni] (MRC CMBI), Imperial College London-Imperial College London, Institute of Molecular Systems Biology [Zurich], Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Instituto de Biologia Molecular e Celular (IBMC), Department of Infectious Diseases and Tropical Medicine [Paris], Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), E.T.S. has been supported by the Swiss National Science Foundation (SNF) grant 310030_156947/1. J.R. was funded by the Deutsche Forschungsgemeinschaft (DFG) grant RI 2920/1-1. A.G. was supported by the Medical Research Council grant MR/P011071/1 and Wellcome Trust grant 100289., Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidade do Porto = University of Porto, Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Bodescot, Myriam, Instituto de Investigação e Inovação em Saúde

المصدر: PLoS Pathogens
PLoS Pathogens, Public Library of Science, 2019, 15 (10), pp.e1008032. ⟨10.1371/journal.ppat.1008032⟩
PLoS Pathogens, 2019, 15 (10), pp.e1008032. ⟨10.1371/journal.ppat.1008032⟩
PLoS Pathogens, 15 (10)
PLoS Pathogens, Vol 15, Iss 10, p e1008032 (2019)

مصطلحات موضوعية: Cell Wall / metabolism, Cell Lines, Pathology and Laboratory Medicine, Physical Chemistry, Cell Wall, 1108 Medical Microbiology, Listeria monocytogenes / metabolism, Medicine and Health Sciences, Bacteriophages, Biology (General), Virulence, Monomers, Hep G2 Cells, Membrane Proteins / metabolism, Bacterial Pathogens, Galactose / metabolism, Chemistry, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Medical Microbiology, 1107 Immunology, Viruses, Physical Sciences, Sorption, Biological Cultures, Pathogens, Cellular Structures and Organelles, Teichoic Acids / metabolism, Research Article, 0605 Microbiology, Bacterial Proteins / genetics, QH301-705.5, Listeria, Virulence Factors, Bacterial Proteins / metabolismo, Research and Analysis Methods, Serogroup, Microbiology, Cell Walls, Bacterial Proteins, Virology, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Microbial Pathogens, Listeria monocytogenes / virology, Membrane Proteins / genetics, Bacteria, Organisms, Biology and Life Sciences, Galactose, Membrane Proteins, Cell Biology, RC581-607, Listeria Monocytogenes, Polymer Chemistry, Bacteriophages / genetics, Teichoic Acids, Bacteriophages / pathogenicity, Mutation, Adsorption, Immunologic diseases. Allergy, Caco-2 Cells

الوصف: The intracellular pathogen Listeria monocytogenes is distinguished by its ability to invade and replicate within mammalian cells. Remarkably, of the 15 serovars within the genus, strains belonging to serovar 4b cause the majority of listeriosis clinical cases and outbreaks. The Listeria O-antigens are defined by subtle structural differences amongst the peptidoglycan-associated wall-teichoic acids (WTAs), and their specific glycosylation patterns. Here, we outline the genetic determinants required for WTA decoration in serovar 4b L. monocytogenes, and demonstrate the exact nature of the 4b-specific antigen. We show that challenge by bacteriophages selects for surviving clones that feature mutations in genes involved in teichoic acid glycosylation, leading to a loss of galactose from both wall teichoic acid and lipoteichoic acid molecules, and a switch from serovar 4b to 4d. Surprisingly, loss of this galactose decoration not only prevents phage adsorption, but leads to a complete loss of surface-associated Internalin B (InlB),the inability to form actin tails, and a virulence attenuation in vivo. We show that InlB specifically recognizes and attaches to galactosylated teichoic acid polymers, and is secreted upon loss of this modification, leading to a drastically reduced cellular invasiveness. Consequently, these phage-insensitive bacteria are unable to interact with cMet and gC1q-R host cell receptors, which normally trigger cellular uptake upon interaction with InlB. Collectively, we provide detailed mechanistic insight into the dual role of a surface antigen crucial for both phage adsorption and cellular invasiveness, demonstrating a trade-off between phage resistance and virulence in this opportunistic pathogen.
Author summary L. monocytogenes is a Gram-positive, food-borne, intracellular pathogen that causes severe infection in susceptible individuals. Interestingly, almost all infections are caused by a subset of strains belonging to certain serovars featuring a complex glycosylation pattern on their cell surface. Using an engineered bacteriophage that specifically recognizes these modifications we selected for mutants that lost these sugars. We found that the resulting strains are severely deficient in invading host cells as we observed that a major virulence factor mediating host cell entry requires galactose decoration of the cell surface for its function. Without this galactose decoration, the strain represents a serovar not associated with disease. Altogether, we show a complex interplay between bacteriophages, bacteria, and the host, demonstrating that cellular invasiveness is dependent upon a serovar-defining structure, which also serves as a phage receptor.

وصف الملف: application/application/pdf; application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::f8ac5b03d06062415b1393964e8c6890Test
http://hdl.handle.net/10044/1/74039Test

المؤلفون: Tom Lenaerts, Nathaniel Mon Père, David Dingli, Jorge M. Pacheco

المساهمون: Physics, Faculty of Sciences and Bioengineering Sciences, Informatics and Applied Informatics, Artificial Intelligence, Universidade do Minho

المصدر: PLoS Computational Biology, Vol 14, Iss 6, p e1006133 (2018)
PLoS Computational Biology
Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
PLoS computational biology, 14 (6

مصطلحات موضوعية: 0301 basic medicine, Physiology, Hemoglobinuria, Paroxysmal, Clone (cell biology), Hemoglobinuria, medicine.disease_cause, Geographical locations, Animal Cells, Medicine and Health Sciences, hematopoïetic stem cells, Cell Cycle and Cell Division, lcsh:QH301-705.5, Genetics, Mutation, Ecology, Stem Cells, Cell Differentiation, Gene Pool, Hemoglobinuria/genetics, Computational Theory and Mathematics, Processus stochastiques, Cell Processes, Modeling and Simulation, Physical Sciences, Gene pool, Cellular Types, Stem cell, Research Article, Markov Models, Biology, Research and Analysis Methods, Models, Biological, Hemoglobinuria, Paroxysmal/genetics, Hematopoiesis/genetics, Evolution, Molecular, 03 medical and health sciences, Cellular and Molecular Neuroscience, Germline mutation, Modelling and Simulation, medicine, Humans, Membrane Proteins/genetics, Molecular Biology Techniques, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Evolutionary Biology, Science & Technology, Population Biology, Membrane Proteins, Biology and Life Sciences, Cell Biology, Hematopoietic Stem Cells, Probability Theory, medicine.disease, United States, Hematopoiesis, Clone Cells, Complement system, 030104 developmental biology, lcsh:Biology (General), North America, Paroxysmal nocturnal hemoglobinuria, People and places, mutation, Physiological Processes, Population Genetics, Mathematics, Hématologie, Cloning, Developmental Biology

الوصف: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal blood disorder characterized by hemolysis and a high risk of thrombosis, that is due to a deficiency in several cell surface proteins that prevent complement activation. Its origin has been traced to a somatic mutation in the PIG-A gene within hematopoietic stem cells (HSC). However, to date the question of how this mutant clone expands in size to contribute significantly to hematopoiesis remains under debate. One hypothesis posits the existence of a selective advantage of PIG-A mutated cells due to an immune mediated attack on normal HSC, but the evidence supporting this hypothesis is inconclusive. An alternative (and simpler) explanation attributes clonal expansion to neutral drift, in which case selection neither favours nor inhibits expansion of PIG-A mutated HSC. Here we examine the implications of the neutral drift model by numerically evolving a Markov chain for the probabilities of all possible outcomes, and investigate the possible occurrence and evolution, within this framework, of multiple independently arising clones within the HSC pool. Predictions of the model agree well with the known incidence of the disease and average age at diagnosis. Notwithstanding the slight difference in clonal expansion rates between our results and those reported in the literature, our model results lead to a relative stability of clone size when averaging multiple cases, in accord with what has been observed in human trials. The probability of a patient harbouring a second clone in the HSC pool was found to be extremely low (~10-8). Thus our results suggest that in clinical cases of PNH where two independent clones of mutant cells are observed, only one of those is likely to have originated in the HSC pool.
SCOPUS: ar.j
info:eu-repo/semantics/published

وصف الملف: application/pdf; 2 full-text file(s): application/vnd.openxmlformats-officedocument.wordprocessingml.document

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2dd286d352f45bde2ac79cabbf462f57Test
http://europepmc.org/articles/PMC6023248?pdf=renderTest

المؤلفون: Ge He, Nicola L. Diny, Abdel Aouacheria, Margaret Dayhoff-Brannigan, Xianghui Chen, Cierra N. Sing, Zachary D. Stolp, Wen Chih Cheng, Mingjun Zhao, Kyle Metz, J. Marie Hardwick, Xinchen Teng, Guiqin Wang, Yu Zhang

المساهمون: Extraction de Caractéristiques et Identification (imagine), Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Beijing National Laboratory for Condensed Matter Physics, Chinese Academy of Sciences [Beijing] (CAS), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Department of Pharmacology and Molecular Sciences, Johns Hopkins University (JHU), National Natural Science Foundation of China 31401197, Natural Science Foundation of Jiangsu Province BK20140318, Jiangsu Key Laboratory of Neuropsychiatric Diseases BM2013003, National Institutes of Health USA [grant numbers R01NS083373 and R01GM077875, Fondation ARC N˚ LS172351, Ligue Contre le Cancer Comité du Gard N˚ LS 176487, Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École Centrale de Lyon (ECL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Université Lumière - Lyon 2 (UL2), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE)

المصدر: PLoS Genetics, Vol 14, Iss 8, p e1007592 (2018)
PLoS Genetics
PLoS Genetics, 2018, 14 (8), pp.e1007592. ⟨10.1371/journal.pgen.1007592⟩
PLoS Genetics, Public Library of Science, 2018, 14 (8), pp.e1007592. ⟨10.1371/journal.pgen.1007592⟩

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], GTPase, MESH: Intracellular Signaling Peptides and Proteins/genetics, Chlorocebus aethiops, Phosphoprotein Phosphatases, Amino Acids, [INFO.INFO-BT]Computer Science [cs]/Biotechnology, Genetics (clinical), chemistry.chemical_classification, MESH: Transcription Factors/metabolism, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Intracellular Signaling Peptides and Proteins, MESH: Gene Expression Regulation, Cell biology, Amino acid, MESH: COS Cells, COS Cells, Saccharomyces cerevisiae Proteins, lcsh:QH426-470, Saccharomyces cerevisiae, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH: Membrane Proteins/genetics, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Skp1, Genetics, Animals, Humans, MESH: Membrane Proteins/metabolism, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], MESH: Transcription Factors/genetics, Molecular Biology, Transcription factor, Ecology, Evolution, Behavior and Systematics, Monomeric GTP-Binding Proteins, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, Membrane Proteins, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, biology.organism_classification, MESH: Cercopithecus aethiops, Yeast, lcsh:Genetics, 030104 developmental biology, Gene Expression Regulation, Membrane protein, chemistry, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Transcription Factors, MESH: Intracellular Signaling Peptides and Proteins/metabolism, Genetic screen

الوصف: International audience; Yeast WHI2 was originally identified in a genetic screen for regulators of cell cycle arrest and later suggested to function in general stress responses. However, the function of Whi2 is unknown. Whi2 has predicted structure and sequence similarity to human KCTD family proteins, which have been implicated in several cancers and are causally associated with neurological disorders but are largely uncharacterized. The identification of conserved functions between these yeast and human proteins may provide insight into disease mechanisms. We report that yeast WHI2 is a new negative regulator of TORC1 required to suppress TORC1 activity and cell growth specifically in response to low amino acids. In contrast to current opinion, WHI2 is dispensable for TORC1 inhibition in low glucose. The only widely conserved mechanism that actively suppresses both yeast and mammalian TORC1 specifically in response to low amino acids is the conserved SEACIT/GATOR1 complex that inactivates the TORC1-activating RAG-like GTPases. Unexpectedly, Whi2 acts independently and simultaneously with these established GATOR1-like Npr2-Npr3-Iml1 and RAG-like Gtr1-Gtr2 complexes, and also acts independently of the PKA pathway. Instead, Whi2 inhibits TORC1 activity through its binding partners, protein phosphatases Psr1 and Psr2, which were previously thought to only regulate amino acid levels downstream of TORC1. Furthermore, the ability to suppress TORC1 is conserved in the SKP1/BTB/POZ domain-containing, Whi2-like human protein KCTD11 but not other KCTD family members tested.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c583efb63eb90e35e76b8524666ee49cTest
https://doi.org/10.1371/journal.pgen.1007592Test

المؤلفون: Julie Bapst, Camille Ansermet, Anna Keppner, Antoine Nobile, Ditte Andreasen, Anne-Marie Mérillat, Sumedha Malsure, Edith Hummler, Marc Maillard, Qing Wang

المصدر: PLoS ONE, Vol 10, Iss 8, p e0135224 (2015)
PLoS One
PLoS ONE
Plos One, vol. 10, no. 8, pp. e0135224

مصطلحات موضوعية: Epithelial sodium channel, Proteases, medicine.medical_specialty, Sodium, Science, Absorption, Physicochemical, Animals, Biological Transport, Cell Membrane/metabolism, Epithelial Sodium Channels/metabolism, Gene Knockout Techniques, Homeostasis, Membrane Proteins/deficiency, Membrane Proteins/genetics, Mice, Serine Endopeptidases/deficiency, Serine Endopeptidases/genetics, Sodium/metabolism, chemistry.chemical_element, Biology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, In vivo, Internal medicine, medicine, Epithelial Sodium Channels, 030304 developmental biology, Serine protease, 0303 health sciences, Multidisciplinary, Aldosterone, urogenital system, Cell Membrane, Serine Endopeptidases, Membrane Proteins, respiratory system, Endocrinology, chemistry, 030220 oncology & carcinogenesis, Knockout mouse, biology.protein, Medicine, hormones, hormone substitutes, and hormone antagonists, Research Article

الوصف: The membrane-bound serine protease CAP2/Tmprss4 has been previously identified in vitro as a positive regulator of the epithelial sodium channel (ENaC). To study its in vivo implication in ENaC-mediated sodium absorption, we generated a knockout mouse model for CAP2/Tmprss4. Mice deficient in CAP2/Tmprss4 were viable, fertile, and did not show any obvious histological abnormalities. Unexpectedly, when challenged with sodium-deficient diet, these mice did not develop any impairment in renal sodium handling as evidenced by normal plasma and urinary sodium and potassium electrolytes, as well as normal aldosterone levels. Despite minor alterations in ENaC mRNA expression, we found no evidence for altered proteolytic cleavage of ENaC subunits. In consequence, ENaC activity, as monitored by the amiloride-sensitive rectal potential difference (ΔPD), was not altered even under dietary sodium restriction. In summary, ENaC-mediated sodium balance is not affected by lack of CAP2/Tmprss4 expression and thus, does not seem to directly control ENaC expression and activity in vivo.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9631bd63ec79b62e0f63c8203a22a042Test
https://doaj.org/article/150db2d379c04a63818ede209b929fa0Test

المؤلفون: Mauld M Lamarque, Julien Papoin, Alan W. Thomas, Magali Roques, Graham Ga Bentley, Martin J. Boulanger, Juliette Morlon-Guyot, Brigitte Vulliez-Le Normand, Stanislas Tomavo, Jean-François Dubremetz, Bart Bw Faber, Clemens Ch Kocken, Maryse Lebrun, Sylvain Fauquenoy, Sébastien Besteiro

المصدر: PLoS Pathogens, Vol 7, Iss 2, p e1001276 (2011)
P L o S Pathogens, 7 (2
PLoS Pathogens

مصطلحات موضوعية: Models, Molecular, Parasites -- genetics -- metabolism -- physiology, Membrane Proteins -- genetics -- metabolism -- physiology, Protozoan Proteins, Connexins, Chlorocebus aethiops, Microbiology/Parasitology, Integral membrane protein, lcsh:QH301-705.5, Cells, Cultured, Conserved Sequence, Protein Binding -- genetics, Host cell membrane, biology, Connexins -- metabolism, Sciences bio-médicales et agricoles, Cell biology, Antigens, Protozoan -- chemistry -- genetics -- metabolism, Infectious Diseases, Rhoptry neck, Microbiology/Cellular Microbiology and Pathogenesis, Toxoplasma, Research Article, Infectious Diseases/Tropical and Travel-Associated Diseases, Protein Binding, lcsh:Immunologic diseases. Allergy, Plasmodium falciparum -- genetics -- metabolism -- physiology, Plasmodium falciparum, Immunology, Antigens, Protozoan, Models, Biological, Microbiology, Host-Parasite Interactions, Cercopithecus aethiops, Apicomplexa, Virology, parasitic diseases, Genetics, Animals, Humans, Parasites, Protein Interaction Domains and Motifs, Protozoan Proteins -- chemistry -- genetics -- metabolism, Secretion, Toxoplasma -- genetics -- metabolism -- physiology, Apical membrane antigen 1, Protein Interaction Domains and Motifs -- genetics, Vero Cells, Molecular Biology, Host-Parasite Interactions -- genetics -- physiology, Rhoptry, Infectious Diseases/Protozoal Infections, Membrane Proteins, Virus Internalization, biology.organism_classification, Apicomplexa -- genetics -- metabolism -- physiology, Membrane protein, lcsh:Biology (General), Parasitology, lcsh:RC581-607

الوصف: Obligate intracellular Apicomplexa parasites share a unique invasion mechanism involving a tight interaction between the host cell and the parasite surfaces called the moving junction (MJ). The MJ, which is the anchoring structure for the invasion process, is formed by secretion of a macromolecular complex (RON2/4/5/8), derived from secretory organelles called rhoptries, into the host cell membrane. AMA1, a protein secreted from micronemes and associated with the parasite surface during invasion, has been shown in vitro to bind the MJ complex through a direct association with RON2. Here we show that RON2 is inserted as an integral membrane protein in the host cell and, using several interaction assays with native or recombinant proteins, we define the region that binds AMA1. Our studies were performed both in Toxoplasma gondii and Plasmodium falciparum and although AMA1 and RON2 proteins have diverged between Apicomplexa species, we show an intra-species conservation of their interaction. More importantly, invasion inhibition assays using recombinant proteins demonstrate that the RON2-AMA1 interaction is crucial for both T. gondii and P. falciparum entry into their host cells. This work provides the first evidence that AMA1 uses the rhoptry neck protein RON2 as a receptor to promote invasion by Apicomplexa parasites.
Author Summary Apicomplexa parasites are obligate intracellular pathogens causing severe diseases such as the deadly malaria or toxoplasmosis. Host cell invasion by these parasites involves the formation of a structure between the apex of the parasite and the host cell membrane called the moving junction (MJ), which is built upon collaboration between secretory organelles from the parasite that insert microneme protein AMA1 in the parasite plasma membrane and a complex of four rhoptry neck (RON2/4/5/8) proteins at the host cell plasma membrane. We have now identified a strong interaction between AMA1 and a C-terminal region of RON2, which is crucial for invasion. In spite of sequence variations in both proteins orthologs from distinct Apicomplexa, we could show that this interaction is functionally conserved and equally important for the invasive process by Toxoplasma gondii and Plasmodium falciparum. These findings open the way for therapeutic approaches that could interfere with key functions of parasitic MJ.

وصف الملف: 1 full-text file(s): application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fe912dcfe19edb9880bed3876a3b7ad7Test
http://europepmc.org/articles/PMC3037350?pdf=renderTest

المؤلفون: Gabriella Ficz, Wolf Reik, Myriam Hemberger, Ray Kit Ng, Wendy Dean, CF Chan, Cassandra R. Farthing, Simon Andrews

المصدر: PLoS Genetics, Vol 4, Iss 6, p e1000116 (2008)
PLoS Genetics

مصطلحات موضوعية: Homeodomain Proteins - Genetics - Metabolism, Male, Cancer Research, Developmental Biology/Germ Cells, Chromosomal Proteins, Non-Histone, Left-Right Determination Factors, Stem Cells - Physiology, Epigenesis, Genetic, Mice, Transforming Growth Factor beta, Membrane Glycoproteins - Genetics - Metabolism, Nuclear Reprogramming, Developmental Biology/Developmental Molecular Mechanisms, Induced pluripotent stem cell, Promoter Regions, Genetic, RNA-Directed DNA Methylation, Genetics (clinical), Molecular Biology/DNA Methylation, Cells, Cultured, Genetics, Genome, Membrane Glycoproteins, Stem Cells, Transforming Growth Factor Beta - Genetics - Metabolism, Gene Expression Regulation, Developmental, Nanog Homeobox Protein, Cellular Reprogramming, Spermatozoa, Developmental Biology/Stem Cells, Neoplasm Proteins, Chromosomal Proteins, Non-Histone - Genetics - Metabolism, DNA methylation, Female, Reprogramming, Research Article, Homeobox protein NANOG, Pluripotent Stem Cells, lcsh:QH426-470, Epidermal Growth Factor - Genetics - Metabolism, Rex1, Cell Biology/Developmental Molecular Mechanisms, Membrane Proteins - Genetics - Metabolism, Mice, Inbred Strains, Biology, Epigenetics of physical exercise, Neoplasm Proteins - Genetics - Metabolism, Genetics and Genomics/Epigenetics, Animals, Molecular Biology, Cell potency, Ecology, Evolution, Behavior and Systematics, Cell Biology/Gene Expression, Homeodomain Proteins, Epidermal Growth Factor, Membrane Proteins, DNA Methylation, Microarray Analysis, lcsh:Genetics, Pluripotent Stem Cells - Physiology, Developmental Biology/Cell Differentiation, Spermatozoa - Physiology

الوصف: DNA methylation patterns are reprogrammed in primordial germ cells and in preimplantation embryos by demethylation and subsequent de novo methylation. It has been suggested that epigenetic reprogramming may be necessary for the embryonic genome to return to a pluripotent state. We have carried out a genome-wide promoter analysis of DNA methylation in mouse embryonic stem (ES) cells, embryonic germ (EG) cells, sperm, trophoblast stem (TS) cells, and primary embryonic fibroblasts (pMEFs). Global clustering analysis shows that methylation patterns of ES cells, EG cells, and sperm are surprisingly similar, suggesting that while the sperm is a highly specialized cell type, its promoter epigenome is already largely reprogrammed and resembles a pluripotent state. Comparisons between pluripotent tissues and pMEFs reveal that a number of pluripotency related genes, including Nanog, Lefty1 and Tdgf1, as well as the nucleosome remodeller Smarcd1, are hypomethylated in stem cells and hypermethylated in differentiated cells. Differences in promoter methylation are associated with significant differences in transcription levels in more than 60% of genes analysed. Our comparative approach to promoter methylation thus identifies gene candidates for the regulation of pluripotency and epigenetic reprogramming. While the sperm genome is, overall, similarly methylated to that of ES and EG cells, there are some key exceptions, including Nanog and Lefty1, that are highly methylated in sperm. Nanog promoter methylation is erased by active and passive demethylation after fertilisation before expression commences in the morula. In ES cells the normally active Nanog promoter is silenced when targeted by de novo methylation. Our study suggests that reprogramming of promoter methylation is one of the key determinants of the epigenetic regulation of pluripotency genes. Epigenetic reprogramming in the germline prior to fertilisation and the reprogramming of key pluripotency genes in the early embryo is thus crucial for transmission of pluripotency. © 2008 Farthing et al.
link_to_subscribed_fulltext

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::527d68282112680943e1cabbf6635dc3Test
http://europepmc.org/articles/PMC2432031?pdf=renderTest

المؤلفون: Rosalynn Ord, Adriana Tami, Colin J. Sutherland

المساهمون: Microbes in Health and Disease (MHD)

المصدر: PLoS ONE, Vol 3, Iss 10, p e3366 (2008)
PLoS ONE, 3(10):e3366. PUBLIC LIBRARY SCIENCE
PLoS ONE

مصطلحات موضوعية: Plasmodium vivax, Protozoan Proteins, Public Health and Epidemiology/Infectious Diseases, lcsh:Medicine, Population genetics, Balancing selection, Linkage Disequilibrium, Gene Frequency, Effective population size, Malaria/genetics, lcsh:Science, Recombination, Genetic, Genetics, education.field_of_study, Multidisciplinary, Antigens, Protozoan/genetics, Protozoan Proteins/genetics, Plasmodium vivax/genetics, Research Article, Plasmodium falciparum, Population, Antigens, Protozoan, Biology, Genetic, Genetics and Genomics/Population Genetics, parasitic diseases, Genetic variation, Animals, Humans, Selection, Genetic, Antigens, Membrane Proteins/genetics, education, Selection, Genetic diversity, Base Sequence, lcsh:R, Infectious Diseases/Protozoal Infections, Plasmodium falciparum/genetics, Membrane Proteins, Genetic Variation, Venezuela, biology.organism_classification, Recombination, Malaria, Genetics, Population, Population bottleneck, Haplotypes, lcsh:Q, Protozoan/genetics

الوصف: BACKGROUND: We present the first population genetic analysis of homologous loci from two sympatric human malaria parasite populations sharing the same human hosts, using full-length sequences of ama1 genes from Plasmodium vivax and P. falciparum collected in the Venezuelan Amazon.METHODOLOGY/PRINCIPAL FINDINGS: Significant differences between the two species were found in genetic diversity at the ama1 locus, with 18 distinct haplotypes identified among the 73 Pvama1 sequences obtained, compared to 6 unique haplotypes from 30 Pfama1 sequences, giving overall diversity estimates of h = 0.9091, and h = 0.538 respectively. Levels of recombination were also found to differ between the species, with P. falciparum exhibiting very little recombination across the 1.77 kb sequence. In contrast, analysis of patterns of nucleotide substitutions provided evidence that polymorphisms in the ama1 gene of both species are maintained by balancing selection, particularly in domain I. The two distinct population structures observed are unlikely to result from different selective forces acting upon the two species, which share both human and mosquito hosts in this setting. Rather, the highly structured P. falciparum population appears to be the result of a population bottleneck, while the much less structured P. vivax population is likely to be derived from an ancient pool of diversity, as reflected in a larger estimate of effective population size for this species. Greatly reduced mosquito transmission in 1997, due to low rainfall prior to the second survey, was associated with far fewer P. falciparum infections, but an increase in P. vivax infections, probably due to hypnozoite activation.CONCLUSIONS/SIGNIFICANCE: The relevance of these findings to putative competitive interactions between these two important human pathogen species is discussed. These results highlight the need for future control interventions to employ strategies targeting each of the parasite species present in endemic areas.

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الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dbc94d74b65f3e63aa056c9dd48968c2Test
https://doi.org/10.1371/journal.pone.0003366Test