14,899 results on '"Department of Pathobiology"'
Search Results
52. Arg375 tunes tetrahydrobiopterin functions and modulates catalysis by inducible nitric oxide synthase
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Mohammed Fadlalla, Ashis Biswas, Jérôme Santolini, Zhi Qiang Wang, Chin Chuan Wei, Dennis J. Stuehr, Mohammad Mahfuzul Haque, Jesús Tejero, Kent State University, Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, affiliation inconnue, Southern Illinois University [Edwardsville] ( SIUE ), Stress Oxydants et Détoxication ( LSOD ), Département Biochimie, Biophysique et Biologie Structurale ( B3S ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), National Institutes of Health Grants GM51491 and CA53914, American Heart Association Beginning Grant-in-aid 0565297B, KSU Farris Innovation Award, KSU Tuscarawas Faculty Professional Development Release Time Award, Southern Illinois University [Edwardsville] (SIUE), Stress Oxydants et Détoxication (LSOD), Département Biochimie, Biophysique et Biologie Structurale (B3S), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
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MECHANISM ,Nitric Oxide Synthase Type II ,Biochemistry ,[ CHIM ] Chemical Sciences ,Protein Structure, Secondary ,Hydroxylation ,chemistry.chemical_compound ,0302 clinical medicine ,ELECTRON-TRANSFER ,Pterin ,Heme ,0303 health sciences ,Tetrahydrobiopterin ,biology ,Nitric oxide synthase ,BINDING-SITE ,Single turn over ,Protein Binding ,inorganic chemicals ,Stereochemistry ,OXYGENASE DOMAIN ,Arginine ,Redox ,Catalysis ,Article ,Cofactor ,Ferrous ,NO ,Inorganic Chemistry ,03 medical and health sciences ,HEME-DIOXY REDUCTION ,[CHIM]Chemical Sciences ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Arg375 ,[ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,030304 developmental biology ,SINGLE-TURNOVER ,Hydrogen Bonding ,Biopterin ,STOPPED-FLOW ANALYSIS ,HYDROXY-L-ARGININE ,RADICAL FORMATION ,chemistry ,Mutagenesis, Site-Directed ,biology.protein ,Steady state (chemistry) ,NEURONAL NO SYNTHASE ,Protein Multimerization ,030217 neurology & neurosurgery ,Midpoint potential - Abstract
International audience; NO synthase enzymes (NOS) support unique single-electron transitions of a bound H(4)B cofactor during catalysis. Previous studies showed that both the pterin structure and surrounding protein residues impact H(4)B redox function during catalysis. A conserved Arg residue (Arg375 in iNOS) forms hydrogen bonds with the H(4)B ring. In order to understand the role of this residue in modulating the function of H(4)B and overall NO synthesis of the enzyme, we generated and characterized three mutants R375D, R375K and R375N of the oxygenase domain of inducible NOS (iNOSoxy). The mutations affected the dimer stability of iNOSoxy and its binding affinity toward substrates and H(4)B to varying degrees. Optical spectra of the ferric, ferrous, ferrous dioxy, ferrous-NO, ferric-NO, and ferrous-CO forms of each mutant were similar to the wild-type. However, mutants displayed somewhat lower heme midpoint potentials and faster ferrous heme-NO complex reactivity with O(2). Unlike the wild-type protein, mutants could not oxidize NOHA to nitrite in a H(2)O(2)-driven reaction. Mutation could potentially change the ferrous dioxy decay rate, H(4)B radical formation rate, and the amount of the Arg hydroxylation during single turnover Arg hydroxylation reaction. All mutants were able to form heterodimers with the iNOS G450A full-length protein and displayed lower NO synthesis activities and uncoupled NADPH consumption. We conclude that the conserved residue Arg375 (1) regulates the tempo and extent of the electron transfer between H(4)B and ferrous dioxy species and (2) controls the reactivity of the heme-based oxidant formed after electron transfer from H(4)B during steady state NO synthesis and H(2)O(2)-driven NOHA oxidation. Thus, Arg375 modulates the redox function of H(4)B and is important in controlling the catalytic function of NOS enzymes.
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- 2012
53. VHH against DARC
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Smolarek, Dorota, Hattab, Claude, Hassanzadeh-Ghassabeh, Gholamreza, Cochet, Sylvie, Gutiérrez, Carlos, De Brevern, Alexandre, Udomsangpetch, Rachanee, Picot, Julien, Grodecka, Magdalena, Wasniowska, Kazimiera, Muyldermans, Serge, Colin, Yves, Le Van Kim, Caroline, Czerwinski, Marcin, Bertrand, Olivier, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polska Akademia Nauk = Polish Academy of Sciences (PAN), Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Cellular and Molecular Immunology, University of California [Irvine] (UCI), University of California-University of California, Department of Molecular and Cellular Interactions, Vrije Universiteit Brussel (VUB), Department Of Animal Medicine And Surgery, University of Las Palmas, Department of Pathobiology, Mahidol University [Bangkok], and D.S. was supported by scholarship from Ambassade de France à Varsovie and from the Flemish government. Project was supported by grant no. N N302 118835 from the Ministry of Science and Higher Education of Poland and in part by a Polonium Partenariat Hubert Curien grant.
- Subjects
MESH: Immunoglobulins ,VHH ,MESH: Carrier Proteins ,Immunoaffinity ,MESH: Recombinant Proteins ,HIV ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,MESH: Animals ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,atypical chemokine receptor ,Cancer ,MESH: Receptors, Cell Surface ,Inflammation ,MESH: Humans ,MESH: Blood Group Antigens ,MESH: Erythrocytes ,MESH: Camels ,MESH: Receptors, Antigen ,MESH: Chemokines ,[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,MESH: Plasmodium vivax ,MESH: Interleukin-8 ,MESH: Duffy Blood-Group System ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] ,Plasmodium vivax ,Duffy Antigen Receptor for Chemokines ,MESH: Receptors, Chemokine - Abstract
International audience; Fy blood group antigens are carried by the Duffy antigen receptor for chemokines (DARC), a red cells receptor for Plasmodium vivax broadly implicated in human health and diseases. Recombinant VHHs, or nanobodies, the smallest intact antigen binding fragment derivative from the heavy chain-only antibodies present in camelids, were prepared from a dromedary immunized against DARC N-terminal extracellular domain and selected for DARC binding. A described VHH, CA52, does recognize native DARC on cells. It inhibits P. vivax invasion of erythrocytes and displaces interleukin-8 bound to DARC. The targeted epitope overlaps the well-defined DARC Fy6 epitope. K (D) of CA52-DARC equilibrium is sub-nanomolar, hence ideal to develop diagnostic or therapeutic compounds. Immunocapture by immobilized CA52 yielded highly purified DARC from engineered K562 cells. This first report on a VHH with specificity for a red blood cell protein exemplifies VHHs' potentialities to target, to purify, and to modulate the function of cellular markers.
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- 2010
54. Detection and molecular analysis of West Nile virus infections in birds of prey in the eastern part of Austria in 2008 and 2009
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Herbert Weissenböck, Susanne Richter, Sandra Revilla-Fernández, Norbert Nowotny, Petra Winter, Eveline Wodak, Zoltán Bagó, Austrian Agency for Health and Food Safety (AGES), Department of Pathobiology, University of Veterinary Medicine, and Zoonoses and Emerging Infections Group
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Male ,viruses ,Enzyme-Linked Immunosorbent Assay ,goshawk ,Antibodies, Viral ,Microbiology ,Virus ,Disease Outbreaks ,Flaviviridae ,Mice ,Neutralization Tests ,medicine ,Animals ,Cells, Cultured ,Phylogeny ,Specific-pathogen-free ,Ovum ,[SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health ,General Veterinary ,biology ,Raptors ,Bird Diseases ,Reverse Transcriptase Polymerase Chain Reaction ,Flavivirus ,Zoonosis ,Antibody titer ,Embryonated ,virus diseases ,Accipiter ,General Medicine ,zoonosis ,biology.organism_classification ,medicine.disease ,Virology ,Austria ,RNA, Viral ,mosquito-borne flavivirus ,Female ,Chickens ,West Nile virus ,West Nile Fever - Abstract
The emergence of West Nile virus (WNV) was expected in Austria since the initial discovery of the infection in neighbouring Hungary in 2003/2004. In 2008 six cases of West Nile disease were diagnosed at the Institute for Veterinary Disease Control Modling, Austrian Agency for Health and Food Safety (AGES), involving five goshawks (Accipiter gentilis) and one gyrfalcon (Falco rusticolus), which were found dead in the eastern Austrian federal states of Lower Austria, Vienna and Styria, respectively. Pathomorphological and immunohistochemical findings suggested a WNV infection. Virus was isolated in embryonated specific pathogen free chicken eggs and propagated in mouse neuroblastoma cells (NA), in which a cytopathic effect occurred. The virus was identified and characterised by electron microscopic examination and molecular detection using RT-PCR, sequencing, and phylogenetic analysis. The Austrian WNV sequences exhibited nucleotide identities of 99.9% to the lineage 2 WNV sequences described in Hungary since 2004. In addition, 71 sera of 14 different bird species were screened for the presence of WNV antibodies using a commercial ELISA: 43.7% of the tested samples showed antibody titers. Selected positive sera were also subjected to WNV neutralisation tests, in which the ELISA results were verified in 66%. The results of this study confirm unambiguously the presence of a lineage 2 WNV infection in birds of prey in the eastern part of Austria.
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- 2010
55. VHH against DARC
- Author
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Alexandre G. de Brevern, Rachanee Udomsangpetch, Caroline Le Van Kim, Kazimiera Wasniowska, Magdalena Grodecka, Claude Hattab, Olivier Bertrand, Serge Muyldermans, Julien Picot, Yves Colin, Dorota Smolarek, Sylvie Cochet, Marcin Czerwinski, Carlos Gutierrez, Gholamreza Hassanzadeh-Ghassabeh, Cellular and Molecular Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polska Akademia Nauk = Polish Academy of Sciences (PAN), Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Cellular and Molecular Immunology, University of California [Irvine] (UCI), University of California-University of California, Department of Molecular and Cellular Interactions, Vrije Universiteit Brussel (VUB), Department Of Animal Medicine And Surgery, University of Las Palmas, Department of Pathobiology, Mahidol University [Bangkok], and D.S. was supported by scholarship from Ambassade de France à Varsovie and from the Flemish government. Project was supported by grant no. N N302 118835 from the Ministry of Science and Higher Education of Poland and in part by a Polonium Partenariat Hubert Curien grant.
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Erythrocytes ,MESH: Immunoglobulins ,Plasmodium vivax ,Epitope ,law.invention ,MESH: Recombinant Proteins ,0302 clinical medicine ,law ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Duffy antigen receptor for chemokines ,MESH: Animals ,Receptor ,MESH: Receptors, Cell Surface ,Cancer ,0303 health sciences ,biology ,MESH: Erythrocytes ,MESH: Camels ,MESH: Receptors, Antigen ,MESH: Chemokines ,[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,Recombinant Proteins ,3. Good health ,MESH: Plasmodium vivax ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Blood Group Antigens ,Recombinant DNA ,Molecular Medicine ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Receptors, Chemokine ,Chemokines ,Antibody ,Camelus ,Immunoglobulins ,Receptors, Cell Surface ,MESH: Carrier Proteins ,VHH ,Article ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,HIV ,Antigen ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,medicine ,Animals ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,atypical chemokine receptor ,Molecular Biology ,030304 developmental biology ,Pharmacology ,MESH: Humans ,MESH: Blood Group Antigens ,Interleukin-8 ,Cell Biology ,biology.organism_classification ,Virology ,Molecular biology ,MESH: Interleukin-8 ,MESH: Duffy Blood-Group System ,immunoaffinity ,Receptors, Antigen ,Red blood cell ,inflammation ,biology.protein ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] ,Carrier Proteins ,Duffy Blood-Group System ,MESH: Receptors, Chemokine ,K562 cells - Abstract
International audience; Fy blood group antigens are carried by the Duffy antigen receptor for chemokines (DARC), a red cells receptor for Plasmodium vivax broadly implicated in human health and diseases. Recombinant VHHs, or nanobodies, the smallest intact antigen binding fragment derivative from the heavy chain-only antibodies present in camelids, were prepared from a dromedary immunized against DARC N-terminal extracellular domain and selected for DARC binding. A described VHH, CA52, does recognize native DARC on cells. It inhibits P. vivax invasion of erythrocytes and displaces interleukin-8 bound to DARC. The targeted epitope overlaps the well-defined DARC Fy6 epitope. K (D) of CA52-DARC equilibrium is sub-nanomolar, hence ideal to develop diagnostic or therapeutic compounds. Immunocapture by immobilized CA52 yielded highly purified DARC from engineered K562 cells. This first report on a VHH with specificity for a red blood cell protein exemplifies VHHs' potentialities to target, to purify, and to modulate the function of cellular markers.
- Published
- 2010
56. A recombinant dromedary antibody fragment (VHH or nanobody) directed against human Duffy antigen receptor for chemokines
- Author
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Smolarek, Dorota, Hattab, Claude, Hassanzadeh-Ghassabeh, Gholamreza, Cochet, Sylvie, Gutiérrez, Carlos, de Brevern, Alexandre, Udomsangpetch, Rachanee, Picot, Julien, Grodecka, Magdalena, Wasniowska, Kazimiera, Muyldermans, Serge, Colin, Yves, Le van Kim, Caroline, Czerwinski, Marcin, Bertrand, Olivier, de Brevern, Alexandre G., Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polska Akademia Nauk = Polish Academy of Sciences (PAN), Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Cellular and Molecular Immunology, University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Department of Molecular and Cellular Interactions, Vrije Universiteit Brussel (VUB), Department Of Animal Medicine And Surgery, University of Las Palmas, Department of Pathobiology, Mahidol University [Bangkok], and D.S. was supported by scholarship from Ambassade de France à Varsovie and from the Flemish government. Project was supported by grant no. N N302 118835 from the Ministry of Science and Higher Education of Poland and in part by a Polonium Partenariat Hubert Curien grant.
- Subjects
MESH: Immunoglobulins ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,VHH ,MESH: Carrier Proteins ,Immunoaffinity ,MESH: Recombinant Proteins ,HIV ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,MESH: Animals ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,atypical chemokine receptor ,Cancer ,[INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM] ,MESH: Receptors, Cell Surface ,Inflammation ,[SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,MESH: Humans ,MESH: Blood Group Antigens ,MESH: Erythrocytes ,MESH: Camels ,MESH: Receptors, Antigen ,MESH: Chemokines ,[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,MESH: Plasmodium vivax ,MESH: Interleukin-8 ,MESH: Duffy Blood-Group System ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] ,Plasmodium vivax ,Duffy Antigen Receptor for Chemokines ,MESH: Receptors, Chemokine - Abstract
International audience; Fy blood group antigens are carried by the Duffy antigen receptor for chemokines (DARC), a red cells receptor for Plasmodium vivax broadly implicated in human health and diseases. Recombinant VHHs, or nanobodies, the smallest intact antigen binding fragment derivative from the heavy chain-only antibodies present in camelids, were prepared from a dromedary immunized against DARC N-terminal extracellular domain and selected for DARC binding. A described VHH, CA52, does recognize native DARC on cells. It inhibits P. vivax invasion of erythrocytes and displaces interleukin-8 bound to DARC. The targeted epitope overlaps the well-defined DARC Fy6 epitope. K (D) of CA52-DARC equilibrium is sub-nanomolar, hence ideal to develop diagnostic or therapeutic compounds. Immunocapture by immobilized CA52 yielded highly purified DARC from engineered K562 cells. This first report on a VHH with specificity for a red blood cell protein exemplifies VHHs' potentialities to target, to purify, and to modulate the function of cellular markers.
- Published
- 2010
57. Fast ferrous heme-NO oxidation in nitric oxide synthases
- Author
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Jérôme Santolini, Dennis J. Stuehr, Jesús Tejero, Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, affiliation inconnue, Stress Oxydants et Détoxication (LSOD), Département Biochimie, Biophysique et Biologie Structurale (B3S), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), National Institutes of Health Grants CA53914, GM51491, HL76491American Heart Association postdoctoral fellowship 0625632B, Stress Oxydants et Détoxication ( LSOD ), Département Biochimie, Biophysique et Biologie Structurale ( B3S ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Institut de Biologie Intégrative de la Cellule ( I2BC ), and Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS )
- Subjects
MECHANISM ,Chemical Phenomena ,Nitric Oxide Synthase Type II ,Nitric Oxide Synthase Type I ,Biochemistry ,TETRAHYDROBIOPTERIN ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Dioxygenase ,Heme ,IN-VIVO ,0303 health sciences ,L-ARGININE ,biology ,Tetrahydrobiopterin ,CO BINDING ,Nitric oxide synthase ,redox ,medicine.drug ,inorganic chemicals ,Hemeprotein ,OXYGENASE DOMAIN ,Redox ,Article ,Nitric oxide ,Ferrous ,FLASH-PHOTOLYSIS ,03 medical and health sciences ,nitric oxide ,medicine ,Animals ,enzyme mechanism ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,[ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Molecular Biology ,KINETICS ,030304 developmental biology ,Cell Biology ,Combinatorial chemistry ,Rats ,FLAVOHEMOGLOBIN ,Oxygen ,chemistry ,heme-thiolate ,DIOXYGENASE ,heme protein ,biology.protein ,Nitric Oxide Synthase ,030217 neurology & neurosurgery - Abstract
International audience; During catalysis, the heme in nitric oxide synthase (NOS) binds NO before releasing it to the environment. Oxidation of the NOS ferrous heme-NO complex by O2 is key for catalytic cycling, but the mechanism is unclear. We utilized stopped-flow methods to study the reaction of O2 with ferrous heme-NO complexes of inducible and neuronal NOS enzymes. We found that the reaction does not involve heme-NO dissociation, but instead proceeds by a rapid direct reaction of O2 with the ferrous heme-NO complex. This behavior is novel and may distinguish heme-thiolate enzymes, such as NOS, from related heme proteins.
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- 2009
58. Comparative sensitivity of harbour and grey seals to several environmental contaminants using in vitro exposure
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S. Pillet, Michel Fournier, S. De Guise, Véronique Lesage, Héloïse Frouin, Marc M. Dufresne, Université du Québec à Montréal = University of Québec in Montréal (UQAM), Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Fisheries and Oceans Canada, Maurice Lamontagne Institute, Department of Pathobiology and Veterinary Science, and University of Connecticut (UCONN)
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Male ,Seals, Earless ,Lymphocyte proliferation ,010501 environmental sciences ,Oceanography ,01 natural sciences ,Chloride ,MESH: Dose-Response Relationship, Drug ,chemistry.chemical_compound ,Cadmium Chloride ,Immunotoxicity ,MESH: Animals ,PCBs ,Lymphocytes ,Methylmercury ,MESH: Cadmium Chloride ,0303 health sciences ,Cadmium ,Immunotoxins ,Harbour seals ,Chlorodiphenyl (54% Chlorine) ,Methylmercury Compounds ,Pollution ,Polychlorinated Biphenyls ,MESH: Water Pollutants, Chemical ,MESH: Cell Survival ,MESH: Phoca ,[SDV.TOX]Life Sciences [q-bio]/Toxicology ,Environmental chemistry ,Mercuric Chloride ,Female ,medicine.drug ,MESH: Methylmercury Compounds ,MERCURE ,Cell Survival ,MESH: Environmental Exposure ,chemistry.chemical_element ,Phoca ,Aquatic Science ,Biology ,Cadmium chloride ,MESH: Immunotoxins ,03 medical and health sciences ,MESH: Cell Proliferation ,Toxicity Tests ,medicine ,Ecotoxicology ,Animals ,MESH: Chlorodiphenyl (54% Chlorine) ,MESH: Mercuric Chloride ,MESH: Seals, Earless ,MESH: Toxicity Tests ,030304 developmental biology ,0105 earth and related environmental sciences ,Cell Proliferation ,Dose-Response Relationship, Drug ,Grey seals ,Mercury ,Environmental Exposure ,MESH: Male ,Mercury (element) ,MESH: Polychlorinated Biphenyls ,chemistry ,MESH: Lymphocytes ,MESH: Female ,Water Pollutants, Chemical - Abstract
In this study, we investigated the effects of cadmium chloride (CdCl 2 ), mercury chloride (HgCl 2 ), methylmercury chloride (CH 3 HgCl), and PCBs on lymphocyte proliferation in phocids. PBMCs isolated from harbour and grey seals were exposed in vitro to varying concentrations of contaminants. A reduction of viability occurred when cells were exposed to 10 −4 M HgCl 2 or CH 3 HgCl or to 50 ppm of Aroclor 1254. In both grey and harbour seals, T-lymphocyte proliferation was suppressed when their cells were incubated with 5 × 10 −5 M CdCl 2 or 10 −4 M HgCl 2 . An inhibition of proliferation occurred with CH 3 HgCl from 10 −6 M in grey seals and from 10 −5 M in harbour seals. In grey seals, Aroclor 1254 reduced lymphocyte proliferation at 15 ppm. In both harbour and grey seals, CH 3 HgCl was ten times more immunotoxic that HgCl 2 . From IC 50 , chemicals were ranked in terms of toxicity as followed: CH 3 HgCl > CdCl 2 > HgCl 2 > Aroclor 1254.
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- 2009
59. Unexpectedly High Proportion of Ancestral Manu Genotype Mycobacterium tuberculosis Strains Cultured from Tuberculosis Patients in Egypt ▿
- Author
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Sankhiros Babapoor, Nalin Rastogi, Ghanem Abd-Elatef, Zeinab H. Helal, Thierry Zozio, Somaia A. Eissa, Mazhar I. Khan, Mohamed Ashour, Department of Microbiology and Immunology, Faculty of Pharmacy, Molecular Biology Laboratory, Department of Pathobiology and Veterinary Science, University of Connecticut (UCONN), Center of Tuberculosis, Department of Microbiology and Immunology, Cairo University - Faculty of Medicine, Department of Chest Diseases, Faculty of Medicine, Al-Azhar University [Gaza] (AUG), Institut Pasteur de la Guadeloupe, Réseau International des Instituts Pasteur (RIIP), and TZ was awarded a Ph.D. fellowship by the European Social Funds through the Regional Council of Guadeloupe. The work done at the Pasteur Institute of Guadeloupe was financed by the European Regional Development Fund, the European Commission (grant ERDF/FEDER, A34-05), and the Regional Council of Guadeloupe (grant CR/08-1612, Biodiversité et Risque Infectieux dans les Modèles Insulaires).
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Male ,MESH: Mycobacterium tuberculosis ,"DNA Fingerprinting" ,"SITVIT2" ,MESH: Egypt ,"Tuberculosis" ,MESH: Genotype ,MESH: Aged, 80 and over ,Genotype ,MESH: DNA Fingerprinting ,Cluster Analysis ,MESH: Tuberculosis ,Clade ,Spoligotyping ,MESH: Aged ,Aged, 80 and over ,Molecular Epidemiology ,MESH: Middle Aged ,biology ,"Spoligotyping" ,"Manu" ,Middle Aged ,Bacterial Typing Techniques ,DNA profiling ,MESH: Young Adult ,Egypt ,Female ,Microbiology (medical) ,Adult ,DNA, Bacterial ,Lineage (genetic) ,Tuberculosis ,Adolescent ,MESH: Bacterial Typing Techniques ,Mycobacterium ,Microbiology ,Mycobacterium tuberculosis ,Young Adult ,"Mycobacterium" ,medicine ,MESH: Molecular Epidemiology ,Humans ,Aged ,MESH: Adolescent ,MESH: Humans ,"Molecular Epidemiology" ,Molecular epidemiology ,MESH: Adult ,Mycobacteriology and Aerobic Actinomycetes ,biology.organism_classification ,medicine.disease ,MESH: Cluster Analysis ,MESH: DNA, Bacterial ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Virology ,DNA Fingerprinting ,MESH: Male ,Manu ,SITVIT2 ,MESH: Female - Abstract
Tuberculosis is one of the important public health problems in Egypt. However, limited information on the Mycobacterium tuberculosis genotypes circulating in Egypt is available. A total of 151 M. tuberculosis strains were characterized by spoligotyping. The results revealed that 74.8% of M. tuberculosis isolates grouped into 13 different clusters, while 25.2% had unique spoligotype patterns. Comparison with an international spoligotyping database (the SITVIT2 database) showed that types SIT53 (T1 variant) and SIT54 (Manu2 variant) were the most common types between cluster groups. In addition, new shared types SIT2977, SIT2978, and SIT2979 were observed. The results identified for the first time an unusually high proportion of ancestral Manu strains of M. tuberculosis from patients in Egypt. The percentage of the Manu clade in this study (27.15%) was significantly higher than its overall representation of 0.4% in the SITVIT2 database. We show that in Egypt tuberculosis is caused by a predominant M. tuberculosis genotype belonging to the ancestral Manu lineage which could be a missing link in the split between ancestral and modern tubercle bacilli during the evolution of M. tuberculosis .
- Published
- 2009
60. Key role of pKa of guanidines in the mechanism of NO synthase
- Author
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Giroud , Claire, Boucher , Jean-Luc, Stuehr , Dennis, Balland , Veronique, Santolini , J., Centre National de la Recherche Scientifique ( CNRS ), Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, affiliation inconnue, Laboratoire d'Electrochimie Moléculaire ( LEM UMR7591 ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Stress Oxydants et Détoxication ( LSOD ), Département Biochimie, Biophysique et Biologie Structurale ( B3S ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Electrochimie Moléculaire (LEM (UMR_7591)), Université Paris Diderot - Paris 7 (UPD7)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Stress Oxydants et Détoxication (LSOD), Département Biochimie, Biophysique et Biologie Structurale (B3S), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Institut de Biologie Intégrative de la Cellule (I2BC), and Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay
- Subjects
[ SDV.BC ] Life Sciences [q-bio]/Cellular Biology ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,[ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2008
61. Inhibitory effects of a series of 7-substituted-indazoles toward nitric oxide synthases: Particular potency of 1H-indazole-7-carbonitrile
- Author
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Jean Luc Boucher, Betty Cottyn, Dominique Vichard, Booma Ramassamy, Daniel Mansuy, Francine Acher, Michel Lepoivre, Luke J. Alvey, Yves Frapart, Dennis J. Stuehr, Institut Jean-Pierre Bourgin (IJPB), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Lavoisier de Versailles (ILV), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CNRS URA 1116, Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, and affiliation inconnue
- Subjects
7-Nitroindazole ,Indazoles ,Nitric Oxide Synthase Type III ,Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Nitric Oxide Synthase Type II ,Nitric Oxide Synthase Type I ,Nitric Oxide ,01 natural sciences ,Biochemistry ,Cofactor ,Catalysis ,Nitric oxide ,Cell Line ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Structure-Activity Relationship ,Drug Discovery ,Structure–activity relationship ,Animals ,[CHIM]Chemical Sciences ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,Indazole ,Binding Sites ,biology ,010405 organic chemistry ,Organic Chemistry ,Active site ,0104 chemical sciences ,3. Good health ,Nitric oxide synthase ,chemistry ,Enzyme inhibitor ,biology.protein ,Molecular Medicine ,Spectrophotometry, Ultraviolet ,Nitric Oxide Synthase - Abstract
A series of new 7-monosubstituted and 3,7-disubstituted indazoles have been prepared and evaluated as inhibitors of nitric oxide synthases (NOS). 1H-Indazole-7-carbonitrile (6) was found equipotent to 7-nitro-1H-indazole (1) and demonstrated preference for constitutive NOS over inducible NOS. By contrast, 1H-indazole-7-carboxamide (8) was slightly less potent but demonstrated a surprising selectivity for the neuronal NOS. Further substitution of 6 by a Br-atom at carbon-3 of the heterocycle enhanced 10-fold the inhibitory effects. Inhibition of NO formation by 6 appeared to be competitive versus both substrate and the cofactor (6R)-5,6,7,8-tetrahydro-L L-biopterin (H 4 B). In close analogies with 1, compound 6 strongly inhibited the NADPH oxi-dase activity of nNOS and induced a spin state transition of the heme-Fe III. Our results are explained with the help of the X-ray structures that identified key-features for binding of 1 at the active site of NOS.
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- 2008
62. Human longevity within an evolutionary perspective: The peculiar paradigm of a postreproductive genetics
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Daniela Mari, Giovannella Baggio, Calogero Caruso, Giovanna De Benedictis, Claudio Franceschi, Miriam Capri, Daniela Monti, Fabiola Olivieri, Stefano Salvioli, Paolo Sansoni, Giuseppe Passarino, Francesca Marchegiani, Sonya Vasto, Giuseppina Candore, CAPRI, M, SALVIOLI, S, MONTI, D, CARUSO, C, CANDORE, G, VASTO, S, OLIVIERI, F, MARCHEGIANI, F, SANSONI, P, BAGGIO, G, MARI, D, PASSARINO, G, DE BENEDICTIS, G, FRANCESCHI, C, Capri M., Salvioli S., Monti D., Caruso C., Vasto S., Olivieri F., Marchegiani F, Sansoni P., Baggio G., Mari D., Passarino G., De Benedictis G., Franceschi C., Department of Experimental Pathology, CIG - Interdepartmental Center 'L.Galvani', Department of Oncology and Experimental Pathology, Department of Pathobiology and Biomedical Methodologies, Università degli studi di Palermo - University of Palermo, Department of Gerontological Sciences, Department of Internal Medicine, University of Parma = Università degli studi di Parma [Parme, Italie], University Hospital, Department of Cell Biology, and Università della Calabria [Arcavacata di Rende] (Unical)
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Male ,Aging ,Mitochondrial DNA ,Genotype ,media_common.quotation_subject ,Longevity ,Population ,Biology ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Genetics ,Humans ,Family ,education ,Molecular Biology ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,media_common ,Aged, 80 and over ,0303 health sciences ,education.field_of_study ,Polymorphism, Genetic ,Reproduction ,Cell Biology ,Adaptation, Physiological ,Biological Evolution ,Phenotype ,Human longevity ,Gene Expression Regulation ,Homo sapiens ,Ageing ,Evolutionary biology ,Trait ,Medicine ,Female ,Identification (biology) ,postreproductive genetics ,030217 neurology & neurosurgery - Abstract
The data we collected on the genetics of human longevity, mostly resulting from studies on centenarians, indicate that: (1) centenarians and long-living sib-pairs are a good choice for the study of human longevity, because they represent an extreme phenotype, i.e., the survival tail of the population who escaped neonatal mortality, pre-antibiotic era illnesses, and fatal outcomes of age-related complex diseases. (2) The model of centenarians is not simply an additional model with respect to well-studied organisms, and the study of humans has revealed characteristics of ageing and longevity (geographical and sex differences, role of antigenic load and inflammation, role of mtDNA variants) which did not emerge from studies in laboratory model systems and organisms. (3) All the phenotypic characteristics of nonagenarians and centenarians fit the hypothesis that ageing is a remodelling process where the body of survivors progressively adapts to internal and external damaging agents they are exposed to during several decades, largely unpredicted by evolution. (4) Such a remodelling process, which can be considered a Darwinian process occurring at the somatic level within the framework of the evolutionary constraints, established by evolution for Homo sapiens as a species, may explain why the same gene polymorphism can have different (beneficial or detrimental) effects at different ages. (5) Geographic and demographic evidence suggest that longevity can be achieved by different combinations of genes, environment, and chance quantitatively and qualitatively different in many geographic areas, and that population-specific genetic factors, play a role on the longevity trait. (6) The concomitant and integrated use of new in silico and high throughput strategies will greatly accelerate the identification of new longevity genes in humans.
- Published
- 2008
63. Costimulatory receptors in a teleost fish: typical CD28, elusive CTLA4
- Author
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Frédérique Michel, J. D. Hansen, David Bernard, Abdenour Benmansour, Béatrice Riteau, Ruth B. Phillips, Pierre Boudinot, Unité de virologie et immunologie moléculaires, Institut National de la Recherche Agronomique (INRA), Department of Pathobiology, University of Washington [Seattle], US Geological Survey [Seattle], United States Geological Survey [Reston] (USGS), School of Biological Sciences [Seattle], Washington State University (WSU), Immunologie Moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), This work was supported by Institut National de la Recherche Agronomique and by Projet Genanimal No. 426, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], United States Geological Survey (USGS), School of Biological Sciences, and Institut Pasteur [Paris]
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Cytoplasm ,MESH: Antigens, CD28 ,Gene Expression ,MESH: Amino Acid Sequence ,MESH: Base Sequence ,MESH: In ,Conserved sequence ,0302 clinical medicine ,Immunology and Allergy ,CTLA-4 Antigen ,MESH: Animals ,Phosphorylation ,Receptor ,Extracellular Signal-Regulated MAP Kinases ,MESH: Extracellular Signal-Regulated MAP Kinases ,MESH: Antigens, CD ,Conserved Sequence ,0303 health sciences ,MESH: Conserved Sequence ,CD28 ,Cell biology ,medicine.anatomical_structure ,Organ Specificity ,Oncorhynchus mykiss ,MESH: Antigens, Differentiation ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,MESH: Computational Biology ,MESH: Gene Expression ,Lymphoid Tissue ,T cell ,Immunology ,Molecular Sequence Data ,Biology ,Chromosomes ,03 medical and health sciences ,CD28 Antigens ,Antigens, CD ,Extracellular ,medicine ,Animals ,Humans ,Amino Acid Sequence ,RNA, Messenger ,Binding site ,030304 developmental biology ,Binding Sites ,MESH: Humans ,Base Sequence ,MESH: Cytoplasm ,T-cell receptor ,Computational Biology ,Antigens, Differentiation ,MESH: Binding Sites ,Interleukin-2 ,Tyrosine ,MESH: Chromosomes ,Sequence Alignment ,030215 immunology - Abstract
T cell activation requires both specific recognition of the peptide-MHC complex by the TCR and additional signals delivered by costimulatory receptors. We have identified rainbow trout sequences similar to CD28 (rbtCD28) and CTLA4 (rbtCTLA4). rbtCD28 and rbtCTLA4 are composed of an extracellular Ig-superfamily V domain, a transmembrane region, and a cytoplasmic tail. The presence of a conserved ligand binding site within the V domain of both molecules suggests that these receptors likely recognize the fish homologues of the B7 family. The mRNA expression pattern of rbtCD28 and rbtCTLA4 in naive trout is reminiscent to that reported in humans and mice, because rbtCTLA4 expression within trout leukocytes was quickly up-regulated following PHA stimulation and virus infection. The cytoplasmic tail of rbtCD28 possesses a typical motif that is conserved in mammalian costimulatory receptors for signaling purposes. A chimeric receptor made of the extracellular domain of human CD28 fused to the cytoplasmic tail of rbtCD28 promoted TCR-induced IL-2 production in a human T cell line, indicating that rbtCD28 is indeed a positive costimulator. The cytoplasmic tail of rbtCTLA4 lacked obvious signaling motifs and accordingly failed to signal when fused to the huCD28 extracellular domain. Interestingly, rbtCTLA4 and rbtCD28 are not positioned on the same chromosome and thus do not belong to a unique costimulatory cluster as in mammals. Finally, our results raise questions about the origin and evolution of positive and negative costimulation in vertebrate immune systems.
- Published
- 2007
64. Detection of Malaria Infection via Latex Agglutination Assay
- Author
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Pramuan Tangboriboonrat, Rachanee Udomsangpetch, and Abdelhamid Elaissari, Duangporn Polpanich, National Nanotechnology Center, National Science and Technology Development Agency [Bangkok] (NSTDA), Department of Chemistry, Mahidol University (Department of Chemistry, Mahidol University), Mahidol University [Bangkok], Laboratoire d'automatique et de génie des procédés (LAGEP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), and Department of Pathobiology
- Subjects
Male ,medicine.drug_class ,[SDV]Life Sciences [q-bio] ,030231 tropical medicine ,Carboxylic Acids ,02 engineering and technology ,Monoclonal antibody ,Sensitivity and Specificity ,Analytical Chemistry ,Microbiology ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,Agglutination Tests ,parasitic diseases ,medicine ,Animals ,Humans ,HSP70 Heat-Shock Proteins ,Malaria, Falciparum ,ComputingMilieux_MISCELLANEOUS ,Immunoassay ,biology ,Chemistry ,Antibodies, Monoclonal ,Plasmodium falciparum ,[CHIM.MATE]Chemical Sciences/Material chemistry ,[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences ,Thailand ,021001 nanoscience & nanotechnology ,medicine.disease ,biology.organism_classification ,3. Good health ,Hsp70 ,Agglutination (biology) ,[CHIM.POLY]Chemical Sciences/Polymers ,Immunoglobulin G ,biology.protein ,Polystyrenes ,Female ,Reagent Kits, Diagnostic ,Antibody ,0210 nano-technology ,Malaria ,Conjugate - Abstract
A rapid test for malaria diagnosis based on specific agglutination of sensitive polystyrene particles containing carboxylic acid with antigen or antibody molecules in the presence of their corresponding antibody or antigen in human plasma has been achieved. The particle-malaria antigen conjugate (PAgC), particle-monoclonal IgG antibody to Plasmodium falciparum heat shock protein 70 conjugate (PmAbC), and particle-polyclonal IgG antibody to P. falciparum malaria conjugate (PpAbC) were prepared via adsorption process. The higher affinity of the malaria antigen adsorption onto particles was observed compared to that of the antibodies. Immunoagglutination of sensitive latex particles was monitored by measuring the change in turbidity, and the aggregate's formation was clearly observed under optical microscope. The efficacy in malaria diagnosis of the conjugated particles evaluated at an outpatient malaria clinic (Mae Sod, Thailand) indicated a success detection of antibody or antigen. Sensitivity of PAgC, PmAbC, and PpAbC for P. falciparum was 84%, 90%, and 90%, respectively, while specificity for malaria disease was 70% for PAgC and 80% for PmAbC and PpAbC. The rapid agglutination-based latex particles assay developed herein showed a great potential for diagnosis of malaria infection.
- Published
- 2007
65. A cDNA microarray for Crassostrea virginica and C. gigas
- Author
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Paul S. Gross, Jonas S. Almeida, Jean Michel Escoubas, David J. McKillen, Yian A. Chen, Isabelle Boutet, Robert W. Chapman, Arnaud Tanguy, Arnaud Huvet, Viviane Boulo, Gregory W. Warr, Z. John Liu, Hal Trent, Evelyne Bachère, Paul Lang, Charles E. Cunningham, Ximing Guo, Matthew J. Jenny, Sylvain De Guise, Dario Moraga, Pauline M. Cupit, Annalaura Mancia, Hollings Marine Laboratory, National Institute of Standards and Technology [Gaithersburg] (NIST), Biology Department (WHOI), Woods Hole Oceanographic Institution (WHOI), South Carolina Department of Natural Resources, Marine Resources Research Institute, Biochemistry and Molecular Biology, Medical University of South Carolina [Charleston] (MUSC), Department of Statistics, Texas AM University, Department of Fisheries and Wildlife, Oregon State University (OSU), Ecologie microbienne des insectes et interactions hôte-pathogène (EMIP), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2), Génome, populations, interactions, adaptation (GPIA), Centre National de la Recherche Scientifique (CNRS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université Montpellier 2 - Sciences et Techniques (UM2), Department of Fisheries and Allied Aquacultures and Program of Cell and Molecular Biosciences, Auburn University (AU), Department of Biology [New Mexico], The University of New Mexico [Albuquerque], Adaptation et diversité en milieu marin (AD2M), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Haskin Shellfish Research Laboratory (HSRL), Rutgers, The State University of New Jersey [New Brunswick] (RU), Rutgers University System (Rutgers)-Rutgers University System (Rutgers), Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Université de Brest (UBO), Physiologie et Ecophysiologie des Mollusques Marins (PE2M), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Department of Pathobiology, University of Connecticut (UCONN), Program in Biomathematics and Biostatistics, The University of Texas Health Science Center at Houston (UTHealth), Department of Biochemistry and Molecular Biology, Université Montpellier 2 - Sciences et Techniques (UM2)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS), Adaptation et diversité en milieu marin (ADMM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Recherche Agronomique (INRA), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0106 biological sciences ,Oyster ,animal structures ,Microarray ,Crassostrea virginica ,Gene Expression ,01 natural sciences ,Applied Microbiology and Biotechnology ,bivalve ,03 medical and health sciences ,Species Specificity ,biology.animal ,Complementary DNA ,Animals ,14. Life underwater ,Crassostrea ,heterologous hybridization ,Crassostrea gigas ,microarray ,oyster ,Gene ,Gene Library ,Oligonucleotide Array Sequence Analysis ,030304 developmental biology ,Genetics ,0303 health sciences ,biology ,Gene Expression Profiling ,010604 marine biology & hydrobiology ,fungi ,Reproducibility of Results ,food and beverages ,Pacific oyster ,biology.organism_classification ,Fishery ,Gene expression profiling ,[SDE]Environmental Sciences ,Eastern oyster - Abstract
International audience; The eastern oyster, Crassostrea virginica, and the Pacific oyster, C. gigas, are species of global economic significance as well as important components of estuarine ecosystems and models for genetic and environmental studies. To enhance the molecular tools available for oyster research, an international group of collaborators has constructed a 27,496-feature cDNA microarray containing 4460 sequences derived from C. virginica, 2320 from C. gigas, and 16 non-oyster DNAs serving as positive and negative controls. The performance of the array was assessed by gene expression profiling using gill and digestive gland RNA derived from both C. gigas and C. virginica, and digestive gland RNA from C. ariakensis. The utility of the microarray for detection of homologous genes by cross-hybridization between species was also assessed and the correlation between hybridization intensity and sequence homology for selected genes determined. The oyster cDNA microarray is publicly available to the research community on a cost-recovery basis.
- Published
- 2007
66. Multilocus sequence typing reveals intrafamilial transmission and microevolutions of Candida albicans isolates from the human digestive tract
- Author
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H. J. Van Kruiningen, Boualem Sendid, Nadine François, S. Veirmeire, Jean-Frederic Colombel, Daniel Poulain, Christiane Bouchier, Marie-Elisabeth Bougnoux, D. Diogo, Christophe d'Enfert, Biologie et Pathogénicité fongiques, Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), Université Paris Descartes - Paris 5 (UPD5), Institut National de la Santé et de la Recherche Médicale (INSERM), University Hospital Gasthuisberg, Institut Pasteur [Paris], Department of Pathobiology, University of Connecticut (UCONN), Biologie et Pathogénicité fongiques (BPF), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP), University Hospital Gasthuisberg [Leuven], Institut Pasteur [Paris] (IP), and ProdInra, Migration
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Microbiology (medical) ,TRANSMISSION ,HUMAN DIGESTIVE TRACT ,Mycology ,Microbiology ,CROHN DISEASE ,Evolution, Molecular ,Loss of heterozygosity ,Feces ,03 medical and health sciences ,Candida albicans ,Genotype ,Humans ,DNA, Fungal ,[SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology ,Phylogeny ,030304 developmental biology ,Genetics ,Mouth ,0303 health sciences ,biology ,030306 microbiology ,Candidiasis ,Fungal genetics ,biology.organism_classification ,Corpus albicans ,EVOLUTION ,Bacterial Typing Techniques ,FAMILY ,Gastrointestinal Tract ,Carriage ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,CARRIER STATE ,Case-Control Studies ,Multilocus sequence typing ,MULTILOCUS SEQUENCE TYPING ,MLST - Abstract
Candida albicans is a human commensal that is also responsible for superficial and systemic infections. Little is known about the carriage of C. albicans in the digestive tract and the genome dynamics that occur during commensalisms of this diploid species. The aim of this study was to evaluate the prevalence, diversity, and genetic relationships among C. albicans isolates recovered during natural colonization of the digestive tract of humans, with emphasis on Crohn's disease patients who produce anti-yeast antibodies and may have altered Candida sp. carriage. Candida sp. isolates were recovered from 234 subjects within 25 families with multiple cases of Crohn's disease and 10 control families, sampled at the oral and fecal sites. Prevalences of Candida sp. and C. albicans carriage were 53.4% and 46.5%, respectively, indicating frequent commensal carriage. No differences in prevalence of carriage could be observed between Crohn's disease patients and healthy subjects. Multilocus sequence typing (MLST) of C. albicans isolates revealed frequent colonization of a subject or several members of the same family by genetically indistinguishable or genetically close isolates. These latter isolates differed by loss-of-heterozygosity events at one or several of the MLST loci. These loss-of-heterozygosity events could be due to either chromosome loss followed by duplication or large mitotic recombination events between complementary chromosomes. This study was the first to jointly assess commensal carriage of C. albicans , intrafamilial transmission, and microevolution. The high frequency of each of these events suggests that the digestive tract provides an important and natural niche for microevolutions of diploid C. albicans through the loss of heterozygosity.
- Published
- 2006
67. What potential of genome-wide integrative approaches to predict vaccine responses?
- Author
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Fany BLANC, Tatiana Maroilley, Marie-Helene Pinard - van der Laan, Gaetan Lemonnier, Jean Jacques Leplat, Edwige Bouguyon, Yvon Billon, Jean Pierre Bidanel, Bertrand Bed'Hom, Jordi Estellé, Sungwon Kim, Lonneke Vervelde, Damer Blake, Claire Rogel Gaillard, Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Université Paris Saclay (COmUE), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), Génétique, Expérimentation et Système Innovants (GenESI), The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Department of Pathobiology and Population Sciences, Royal Veterinary College, European Federation of Animal Science (EAAP). INT., and European Project: 633184,H2020,H2020-SFS-2014-2,SAPHIR(2015)
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[SDV.GEN]Life Sciences [q-bio]/Genetics ,[SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics ,[SDV]Life Sciences [q-bio] ,[INFO]Computer Science [cs] ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
68. Detection of PIK3CA hotspot mutations in canine mammary tumors using droplet digital PCR: tissue validation and liquid biopsy feasibility.
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Seung BJ and Sur JH
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- Dogs, Animals, Female, Liquid Biopsy methods, High-Throughput Nucleotide Sequencing methods, Feasibility Studies, Sensitivity and Specificity, Biomarkers, Tumor genetics, Class I Phosphatidylinositol 3-Kinases genetics, Mammary Neoplasms, Animal genetics, Mammary Neoplasms, Animal pathology, Mammary Neoplasms, Animal diagnosis, Mutation, Polymerase Chain Reaction methods, Dog Diseases genetics, Dog Diseases diagnosis, Dog Diseases pathology
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Domestic dogs (Canis lupus familiaris) serve as valuable translational models for human cancer research due to their biological similarities. Canine mammary tumors (CMTs), frequently diagnosed in female dogs, share various characteristics with human breast cancers. This study investigates the PIK3CA (H1047R) mutation in CMTs using droplet digital PCR (ddPCR) and explores the potential of liquid biopsy for non-invasive detection. We analyzed 80 formalin-fixed, paraffin-embedded (FFPE) CMT tissue samples and compared ddPCR results with next-generation sequencing (NGS) data, achieving high concordance. Plasma and serum samples were also assessed for mutation concordance with tissue results. Our findings indicate a higher frequency of the PIK3CA (H1047R) mutations in benign and grade I malignant CMTs compared to more aggressive malignancies. The ddPCR assay demonstrated high sensitivity and specificity, with plasma testing showing 78.6% sensitivity and 87.5% specificity, and serum testing showing 66.7% sensitivity and 90.0% specificity. These results highlight the viability of liquid biopsy as a minimally invasive method for monitoring PIK3CA mutations in canine patients. The study suggests that liquid biopsy techniques hold significant promise for improving the early detection and monitoring of canine cancers, warranting further research to refine these methods and explore their applications in canine cancer diagnostics and treatment., (© 2024. The Author(s).)
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- 2024
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69. Preliminary study of molecular identification of Mycobacterium bovis from cow's milk in Lorestan (Iran).
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Zahrakar A, Rashidian E, Jaydari A, and Rahimi H
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- Animals, Cattle, Iran, DNA, Bacterial genetics, Female, Polymerase Chain Reaction, Mycobacterium bovis genetics, Mycobacterium bovis isolation & purification, Milk microbiology, Tuberculosis, Bovine microbiology
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Bovine tuberculosis is one of the most important common infectious diseases between humans and livestock. Cow's milk can be investigated as one of the transmission reservoirs of the disease. Our study was conducted to investigate the presence of Mycobacterium bovis (M. bovis) DNA in cow's milk from different regions of Lorestan province using Touch-down PCR (TD-PCR) method. So, 100 milk samples from industrial and traditional cattle farms were collected and evaluated according to the animal breed, the average age of the animal and the region where the animal was kept. Seven (26.9%) out of the 26 cow's milk samples contaminated with Mycobacterium spp., were diagnosed as M. bovis positive. The cattle with an average age of more than 5 years were most infected with Mycobacterium. Also, the crossbred cattle with an average age of 3 to 5 years, which were kept and raised in tropical areas, showed the highest rate of M. bovis infection. Based on our knowledge, this is the first study regarding the presence of Mycobacterium in cow's milk in Iran., (© 2024. The Author(s).)
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- 2024
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70. Distribution of lineages and type II toxin-antitoxin systems among rifampin-resistant Mycobacterium Tuberculosis Isolates.
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Shafipour M, Mohammadzadeh A, Mahmoodi P, Dehghanpour M, and Ghaemi EA
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- Microbial Sensitivity Tests, Drug Resistance, Bacterial genetics, Humans, Iran, Antitubercular Agents pharmacology, Mycobacterium tuberculosis genetics, Mycobacterium tuberculosis drug effects, Toxin-Antitoxin Systems genetics, Rifampin pharmacology, Mutation, Bacterial Proteins genetics, Bacterial Proteins metabolism
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Type II toxin-antitoxin systems such as mazEF3, vapBC3, and relJK play a role in antibiotic resistance and tolerance. Among the different known TA systems, mazEF3, vapBC3, and relJK, which are type II systems, have specific roles in drug resistance. Therefore, the aim of this study was to investigate the mutations in these genes in sensitive and resistant isolates of Mycobacterium tuberculosis. Thirty-two rifampin-resistant and 121 rifampin-sensitive M. tuberculosis isolates were collected from various regions of Iran. Lineage typing was performed using the ASO-PCR method. Mutations in the rpoB gene were analyzed in all isolates by MAS-PCR. Furthermore, mutations in the mazEF3, relJK, and vapBC3 genes of the type II toxin system were assessed through PCR sequencing. These sequences were analyzed using COBALT and SnapGene 2017, and submitted to the GenBank database. Among the 153 M. tuberculosis samples, lineages 4, 3 and 2 were the most common. Lineage 2 had the highest rate of rifampin resistance. Mutations in rpoB531 were the most frequent in resistant isolates. Examination of the toxin-antitoxin system showed that rifampin-resistant isolates belonging to lineage 3 had mutations in either the toxin or antitoxin parts of all three TA systems. A mutation in nucleotide 195 (codon 65) of mazF3 leading to an amino acid change from threonine to isoleucine was detected in all rifampin-resistant isolates. M. tuberculosis isolates belonging to lineage 2 exhibited the highest rifampin resistance in our study. Identifying the mutation in mazF3 in all rifampin-resistant isolates can highlight the significance of this mutation in the development of drug resistance in M. tuberculosis. Expanding the sample size in future studies can help develop a new method for identifying resistant isolates., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shafipour et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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71. Association of time to start of enteral nutrition and outcome in cats with hepatic lipidosis.
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Wallace OP, Jablonski SA, Thomas JS, Bock JH 3rd, and Langlois DK
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Background: Enteral nutrition (EN) is essential for management of hepatic lipidosis (HL) in cats., Objectives: To determine if time to start of EN and other clinicopathologic variables are associated with outcome in cats with HL., Animals: Forty-eight cats with HL., Methods: Retrospective study. Information retrieved from medical records and client communications included clinicopathologic findings, time to start of EN, initial % of resting energy requirements provided, type of feeding tube, duration of hospitalization, and 3-month survival. Variables were compared between surviving and nonsurviving cats and between cats fed ≤12 hours and >12 hours after hospital admission. Multivariable statistical testing was performed to further investigate variables of interest., Results: Seventeen of 25 (68%) cats fed ≤12 hours and 13 of 23 (57%) of cats fed >12 hours after hospital admission survived (P = .55). Only increasing age (odds ratio [OR], 1.313; 95% confidence interval [CI], 1.032-1.671; P = .03) and the presence of ascites (OR, 6.415; 95% CI, 1.354-30.395; P = .02) were associated with death in multivariable analysis. Hospitalization duration (median, interquartile range [IQR]) was shorter in cats fed >12 hours (2.8 days; IQR, 2.1-3.8 days) as compared with cats fed ≤12 hours (4.8 days; IQR, 3.6-6.2 days) after hospital admission (P < .001)., Conclusions and Clinical Importance: An initial stabilization period before EN introduction does not decrease survival or increase duration of hospitalization in cats with HL., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)
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- 2024
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72. Apigenin's Influence on Inflammatory and Epigenetic Responses in Rat Lungs After Radiotherapy.
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Rajabinasab F, Hajimirzaei P, Ramezani F, Moayer F, Gorjipour F, Nikoofar A, Hasanzadeh L, Hamblin MR, Janzadeh A, and Paydar R
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Introduction: The lung is a moderately radio-sensitive organ. When cells are damaged due to accidental radiation exposure or treatment, they release molecules that lead to the recruitment of immune cells, accumulating inflammatory cytokines at the site of damage. Apigenin (Api) is a natural flavonoid known for its anti-inflammatory properties. In this study, we investigated the radioprotective properties of Api in the lung., Methods: Thirty-six Wistar rats were randomly assigned to nine groups: control, radiation (Rad), CMC+Rad, Api10+Rad, and Api20+Rad. Api was administered with an intraperitoneal injection for 7 days, after which the rats were irradiated with 6 Gy whole-body X-ray. At 6 and 72 hours post-irradiation, the rats were euthanized, and their lung tissue was extracted., Results: Radiation led to increased alveolar wall thickness and the infiltration of macrophages and lymphocytes. Furthermore, the expression levels of inflammatory factors such as a nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-ĸB), Glycogen synthase kinase-3 beta (GSK-3β), transforming growth factor-beta1 (TGF-β1), and epigenetic factors including DNA methyltransferase 3a (DNMT3a) and Histone deacetylase 2 (HDAC2) were elevated in the lung tissue following radiation. Meanwhile, the expression level of IκB-α decreased. However, administration of Api (at both 10&20 mg/kg) reversed the adverse effects of radiation., Conclusion: Api administration mitigated radiation-induced lung damage by reversing inflammatory and epigenetic changes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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- 2024
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73. Risk factors associated with antibiotic prescriptions for cases of enteric pathogens in Canada, 2015-2019.
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Dougherty B, Finley R, Dumoulin D, Weese JS, Harper S, Parmley EJ, and Papadopoulos A
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- Humans, Canada epidemiology, Male, Female, Adult, Middle Aged, Risk Factors, Adolescent, Young Adult, Aged, Child, Child, Preschool, Infant, Aged, 80 and over, Antimicrobial Stewardship, Drug Prescriptions statistics & numerical data, Diarrhea drug therapy, Diarrhea epidemiology, Diarrhea microbiology, Infant, Newborn, Anti-Bacterial Agents therapeutic use
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Inappropriate antibiotic use is a key driver of antibiotic resistance and one that can be mitigated through stewardship. A better understanding of current prescribing practices is needed to develop successful stewardship efforts. This study aims to identify factors that are associated with human cases of enteric illness receiving an antibiotic prescription. Cases of laboratory-confirmed enteric illness reported to the FoodNet Canada surveillance system between 2015 and 2019 were the subjects of this study. Laboratory data were combined with self-reported data collected from an enhanced case questionnaire that included demographic data, illness duration and symptoms, and antibiotic prescribing. The data were used to build univariable logistic regression models and a multivariable logistic regression model to explore what factors were associated with a case receiving an antibiotic prescription. The final multivariable model identified several factors as being significantly associated with cases being prescribed an antibiotic. Some of the identified associations indicate that current antibiotic prescribing practices include a substantial level of inappropriate use. This study provides evidence that antibiotic stewardship initiatives targeting infectious diarrhoea are needed to optimize antibiotic use and combat the rise of antibiotic resistance.
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- 2024
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74. The host tropism of current zoonotic H7N9 viruses depends mainly on an acid-labile hemagglutinin with a single amino acid mutation in the stalk region.
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Daidoji T, Sadakane H, Garan K, Kawashita N, Arai Y, Watanabe Y, and Nakaya T
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- Animals, Humans, Mice, Viral Tropism, Influenza in Birds virology, Mutation, Orthomyxoviridae Infections virology, Mice, Inbred BALB C, Zoonoses virology, Host Tropism, Influenza A Virus, H7N9 Subtype genetics, Influenza A Virus, H7N9 Subtype pathogenicity, Hemagglutinin Glycoproteins, Influenza Virus genetics, Hemagglutinin Glycoproteins, Influenza Virus metabolism, Influenza, Human virology
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The incidence of human infection by zoonotic avian influenza viruses, especially H5N1 and H7N9 viruses, has increased. Current zoonotic H7N9 avian influenza viruses (identified since 2013) emerged during reassortment of viruses belonging to different subtypes. Despite analyses of their genetic background, we do not know why current H7N9 viruses are zoonotic. Therefore, there is a need to identify the factor(s) responsible for the extended host tropism that enables these viruses to infect humans as well as birds. To identify H7N9-specific amino acids that confer zoonotic properties on H7N9 viruses, we performed multiple alignment of the hemagglutinin (HA) amino acid sequences of A/Shanghai/1/2013 (H7N9) and A/duck/Zhejiang/12/2011(H7N3) (a putative, non- or less zoonotic HA donor to the zoonotic H7N9 virus). We also analyze the function of an H7N9 HA-specific amino acid with respect to HA acid stability, and evaluated the effect of acid stability on viral infectivity and virulence in a mouse model. HA2-116D, preserved in current zoonotic H7N9 viruses, was crucial for loss of HA acid stability. The acid-labile HA protein in H7 viruses played an important role in infection of human airway epithelial cells; HA2-116D contributed to infection and replication of H7 viruses. Finally, HA2-116D served as a H7 virulence factor in mice. These results suggest that acid-labile HA harboring HA2-116D confers zoonotic characteristics on H7N9 virus and that future novel zoonotic avian viruses could emerge from non-zoonotic H7 viruses via acquisition of mutations that remove HA acid stability., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Daidoji et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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75. Neu5Gc binding loss of subtype H7 influenza A virus facilitates adaptation to gallinaceous poultry following transmission from waterbirds.
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Guan M, DeLiberto TJ, Feng A, Zhang J, Li T, Wang S, Li L, Killian ML, Praena B, Giri E, Deliberto ST, Hang J, Olivier A, Torchetti MK, Tao YJ, Parrish C, and Wan X-F
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- Animals, N-Acetylneuraminic Acid metabolism, Influenza A Virus, H7N9 Subtype genetics, Influenza A Virus, H7N9 Subtype pathogenicity, China, Humans, Hemagglutinin Glycoproteins, Influenza Virus metabolism, Hemagglutinin Glycoproteins, Influenza Virus genetics, Poultry Diseases virology, Poultry Diseases transmission, Poultry Diseases metabolism, Poultry virology, Influenza in Birds virology, Influenza in Birds transmission, Chickens virology, Ducks virology, Neuraminic Acids metabolism, Virus Replication
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Between 2013 and 2018, the novel A/Anhui/1/2013 (AH/13)-lineage H7N9 virus caused at least five waves of outbreaks in humans, totaling 1,567 confirmed human cases in China. Surveillance data indicated a disproportionate distribution of poultry infected with this AH/13-lineage virus, and laboratory experiments demonstrated that this virus can efficiently spread among chickens but not among Pekin ducks. The underlying mechanism of this selective transmission remains unclear. In this study, we demonstrated the absence of Neu5Gc expression in chickens across all respiratory and gastrointestinal tissues. However, Neu5Gc expression varied among different duck species and even within the tissues of the same species. The AH/13-lineage viruses exclusively bind to acetylneuraminic acid (Neu5Ac), in contrast to wild waterbird H7 viruses that bind both Neu5Ac and N-glycolylneuraminic acid (Neu5Gc). The level of Neu5Gc expression influences H7 virus replication and facilitates adaptive mutations in these viruses. In summary, our findings highlight the critical role of Neu5Gc in affecting the host range and interspecies transmission dynamics of H7 viruses among avian species.IMPORTANCEMigratory waterfowl, gulls, and shorebirds are natural reservoirs for influenza A viruses (IAVs) that can occasionally spill over to domestic poultry, and ultimately humans. This study showed wild-type H7 IAVs from waterbirds initially bind to glycan receptors terminated with N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc). However, after enzootic transmission in chickens, the viruses exclusively bind to Neu5Ac. The absence of Neu5Gc expression in gallinaceous poultry, particularly chickens, exerts selective pressure, shaping IAV populations, and promoting the acquisition of adaptive amino acid substitutions in the hemagglutinin protein. This results in the loss of Neu5Gc binding and an increase in virus transmissibility in gallinaceous poultry, particularly chickens. Consequently, the transmission capability of these poultry-adapted H7 IAVs in wild water birds decreases. Timely intervention, such as stamping out, may help reduce virus adaptation to domestic chicken populations and lower the risk of enzootic outbreaks, including those caused by IAVs exhibiting high pathogenicity., Competing Interests: The authors declare no conflict of interest.
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- 2024
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76. Clinical and laboratory predictors for bacteremia in critically ill calves.
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Pas ML, Bokma J, Boyen F, and Pardon B
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Background: Sepsis is a main contributor to calf mortality, but diagnosis is difficult., Objectives: Develop and validate a predictive model for bacteremia in critically ill calves (CIC)., Animals: A total of 334 CIC, sampled for blood culture., Methods: Cross-sectional study. Multivariable logistic regression and classification tree analysis on clinical, ultrasonographic, and laboratory variables were performed on a dataset including all animals. Model validation was done on 30% of the dataset. Similar statistics (except validation) were performed on a subset of the database (n = 143), in which presumed contaminants were excluded., Results: The best performing model to predict bacteremia, taking all detected bacteria into account, included tachypnea, tachycardia, acidemia, hypoglycemia, venous hypoxemia, and hypoproteinemia. Sensitivity and specificity of this model were 70.6% and 98.0%, respectively, but decreased to 61.5% and 91.7% during model validation. The best-performing model, excluding presumed contaminants, included abnormal temperature, heart rate, absence of enteritis, hypocalcemia, and hyperlactatemia as risk factors for bacteremia. Sensitivity and specificity of this model were 71.4% and 93.9%, respectively. Both classification trees performed less well in comparison to logistic regression. The classification tree excluding presumed contaminants, featured hypoglycemia, absence of diarrhea, and hyperlactatemia as risk factors for bacteremia. Sensitivity and specificity were 39.4% and 92.7%, respectively., Conclusions and Clinical Importance: Hypoglycemia, hyperlactatemia, and hypoproteinemia seem relevant in assessing bacteremia in CIC. The performance of these models based on basic clinical and blood variables remains insufficient to predict bacteremia., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)
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- 2024
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77. Enhanced docetaxel therapeutic effect using dual targeted SRL-2 and TA1 aptamer conjugated micelles in inhibition Balb/c mice breast cancer model.
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Taghipour YD, Zarebkohan A, Salehi R, Talebi M, Rahbarghazi R, Khordadmehr M, Khavandkari S, Badparvar F, and Torchilin VP
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- Animals, Female, Humans, Mice, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Apoptosis drug effects, Cell Line, Tumor, Drug Delivery Systems, Mice, Inbred BALB C, Nanoparticles chemistry, Tumor Microenvironment drug effects, Aptamers, Nucleotide chemistry, Aptamers, Nucleotide pharmacology, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Docetaxel pharmacology, Docetaxel chemistry, Micelles
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Effective targeting and delivery of large amounts of medications into the cancer cells enhance their therapeutic efficacy through saturation of cellular defensive mechanisms, which is the most privilege of nano drug delivery systems (NDDS) compared to traditional approaches. Herein, we designed dual-pH/redox responsive DTX-loaded poly (β-amino ester) (PBAS) micelles decorated with a chimeric peptide and TA1 aptamer. In vitro and in vivo results demonstrated that the designed nanoplatform possessed an undetectable nature in the blood circulation, but after exposure to the tumor microenvironment (TME) of 4T1 breast cancer, it suddenly changed into dual targeting nanoparticles (NPs) (containing two ligands, SRL-2 and TA1 aptamer). The dual targeting NPs destruction in the high GSH and low pH conditions of the cancer cells led to amplified DTX release (around 70% at 24 h). The IC50 value of DTX-loaded MMP-9 sensitive heptapeptide/TA1 aptamer-modified poly (β-amino ester) (MST@PBAS) micelles and free DTX after 48 h of exposure was determined to be 1.5 µg/ml and 7.5 µg/ml, respectively. The nano-formulated DTX exhibited cytotoxicity that was 5-fold stronger than free DTX (Pvalue˂0.001). Cell cycle assay test results showed that following exposure to MST@PBAS micelles, a considerable rise in the sub G1 population (48%) suggested that apoptosis by cell cycle arrest had occurred. DTX-loaded MST@PBAS micelles revealed significantly higher (Pvalue ˂ 0.001) levels of early apoptosis (59.8%) than free DTX (44.7%). Interestingly, in vitro uptake studies showed a significantly higher TME accumulation of dual targeted NPs (6-fold) compared to single targeted NPs (Pvalue < 0.001) which further confirmed by in vivo biodistribution and fluorescent TUNEL assay experiments. NPs treated groups demonstrated notable tumor growth inhibition in 4T1 tumor bearing Balb/c mice by only 1/10th of the DTX therapeutic dose (TD) as a drug model. In conclusion, cleverly designed nanostructures here demonstrated improved anticancer effects by enhancing tumor targeting, delivering chemotherapeutic agents more accurately, promoting drug release, reducing the therapeutic dosage, and lowering side effects of anticancer drugs., (© 2024. The Author(s).)
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- 2024
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78. Induction of chronic asthma up regulated the transcription of senile factors in male rats.
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Hassanzadeh-Khanmiri M, Keyhanmanesh R, Mosaddeghi-Heris R, Delkhosh A, Rezaie J, Taghizadeh S, Sara MRS, and Ahmadi M
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- Animals, Male, Rats, NF-kappa B metabolism, beta-Galactosidase metabolism, Interleukin-1beta metabolism, Interleukin-1beta genetics, Ovalbumin, SOXB1 Transcription Factors metabolism, SOXB1 Transcription Factors genetics, Chronic Disease, Up-Regulation, Disease Models, Animal, Transcription, Genetic, Asthma metabolism, Asthma chemically induced, Asthma genetics, Asthma pathology, Lung metabolism, Lung pathology, Cellular Senescence genetics, Glucuronidase metabolism, Glucuronidase genetics
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Background: The main characteristic of asthma is chronic inflammation. We examined cellular senescence by histology and molecular assay in the lungs of a rat model of asthma. This model comprises sensitization by several intraperitoneal injections of ovalbumin with aluminium hydroxide, followed by aerosol challenges every other day., Results: Data showed that asthma induction caused histological changes including, hyperemia, interstitial pneumonia, fibrinogen clots, and accumulation of inflammatory cells in the pleura. There is an elevation of IL-1β and NF-kB proteins in the asthmatic group (P < 0.001) compared to the control group. The expression of ß-galactosidase increased (P < 0.01), while the expression of Klotho and Sox2 genes was decreased in the lung tissue of the asthmatic group (P < 0.01)., Conclusion: Taken together, these findings suggest that asthmatic conditions accelerated the cellular senescence in the lung tissue., (© 2024. The Author(s).)
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- 2024
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79. Impact of soluble epoxide hydrolase inhibition on silica-induced pulmonary fibrosis, ectopic lymphoid neogenesis, and autoantibody production in lupus-prone mice.
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McDonald OF, Wagner JG, Lewandowski RP, Heine LK, Estrada V, Pourmand E, Singhal M, Harkema JR, Lee KSS, and Pestka JJ
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Objective: Acute intranasal (IN) instillation of lupus-prone NZBWF1 mice with crystalline silica (cSiO
2 ) triggers robust lung inflammation that drives autoimmunity. Prior studies in other preclinical models show that soluble epoxide hydrolase (sEH) inhibition upregulates pro-resolving lipid metabolites that are protective against pulmonary inflammation. Herein, we assessed in NZBWF1 mice how acute IN cSiO2 exposure with or without the selective sEH inhibitor TPPU influences lipidomic, transcriptomic, proteomic, and histopathological biomarkers of inflammation, fibrosis, and autoimmunity., Methods: Female 6-week-old NZBWF1 mice were fed control or TPPU-supplemented diets for 2 weeks then IN instilled with 2.5 mg cSiO2 or saline vehicle. Cohorts were terminated at 7 or 28 days post-cSiO2 instillation (PI) and lungs analyzed for prostaglandins, cytokines/chemokines, gene expression, differential cell counts, histopathology, and autoantibodies., Results: cSiO2 -treatment induced prostaglandins, cytokines/chemokine, proinflammatory gene expression, CD206+ monocytes, Ly6B.2+ neutrophils, CD3+ T cells, CD45R+ B cells, centriacinar inflammation, collagen deposition, ectopic lymphoid structure neogenesis, and autoantibodies. While TPPU effectively inhibited sEH as reflected by skewed lipidomic profile in lung and decreased cSiO2 -induced monocytes, neutrophils, and lymphocytes in lung lavage fluid, it did not significantly impact other biomarkers., Discussion: cSiO2 evoked robust pulmonary inflammation and fibrosis in NZBWF1 mice that was evident at 7 days PI and progressed to ELS development and autoimmunity by 28 days PI. sEH inhibition by TPPU modestly suppressed cSiO2 -induced cellularity changes and pulmonary fibrosis. However, TPPU did not affect ELS formation or autoantibody responses, suggesting sEH minimally impacts cSiO2 -triggered lung inflammation, fibrosis, and early autoimmunity in our model.- Published
- 2024
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80. Regional Variations in and Key Predictors of Feline Tumor Malignancy: A Decade-Long Retrospective Study in Korea.
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Seung BJ, Bae MK, and Sur JH
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Feline cancer is increasingly recognized as a major cause of mortality, yet data on tumor prevalence and behavior in cats, particularly in non-Western regions, remain limited. This study analyzed a decade of feline tumor data in Korea from 2012 to 2022, focusing on age, breed, and anatomical location as predictors of malignancy. Data were collected from 683 cats, with regression analysis applied to determine significant associations. Older cats exhibited a markedly higher risk of malignancy, particularly in mast cell and mammary tumors. Tumors in the mammary gland and alimentary tract had malignancy rates exceeding 90%, underscoring the need for early detection in these regions. Interestingly, squamous cell carcinoma was rare in the skin, in stark contrast to Western studies, likely reflecting differences in environmental exposure. While breed was not a statistically significant predictor, certain breeds, including Persians and Russian Blues, showed a higher frequency of malignancy. These findings highlight the importance of regional tumor research in cats and the need for larger, multicenter datasets that incorporate environmental, genetic, and lifestyle factors. Understanding these influences will help refine veterinary care and improve cancer treatment outcomes in feline populations.
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- 2024
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81. Role of CD163 in PRRSV infection.
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Rowland RRR and Brandariz-Nuñez A
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Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly infectious agent that poses a significant economic threat to the global swine industry. Efficient viral entry relies on interactions with cellular receptors, with CD163-a cysteine-rich scavenger receptor found on porcine alveolar macrophages (PAMs)-playing a critical role. Extensive evidence supports CD163's essential function in PRRSV infection. This review synthesizes current knowledge about CD163's role, examining its structure-function relationship and identifying specific regions crucial for viral entry. We evaluate the established role of CD163 in PRRSV pathogenesis and highlight areas requiring further investigation, along with the potential for targeted therapeutic interventions. Understanding the molecular determinants of CD163's function is vital for developing effective strategies to control PRRSV infection and mitigate its economic impact on swine production. Further research into the PRRSV-CD163 interactions will be crucial for creating novel antiviral strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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82. Swine NONO promotes IRF3-mediated antiviral immune response by Detecting PRRSV N protein.
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Jiang D, Sui C, Wu X, Jiang P, Bai J, Hu Y, Cong X, Li J, Yoo D, Miller LC, Lee C, Du Y, and Qi J
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- Animals, Swine, Humans, Interferon-beta metabolism, Interferon-beta immunology, Signal Transduction, Nucleocapsid Proteins immunology, Nucleocapsid Proteins metabolism, HEK293 Cells, Cell Line, Immunity, Innate, Porcine respiratory and reproductive syndrome virus immunology, Interferon Regulatory Factor-3 metabolism, Porcine Reproductive and Respiratory Syndrome immunology, Porcine Reproductive and Respiratory Syndrome metabolism, Porcine Reproductive and Respiratory Syndrome virology, Virus Replication
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Non-POU domain-containing octamer-binding protein (NONO) is a multi-functional nuclear protein which belongs to the Drosophila behavior/human splicing (DBHS) protein family. NONO is known to regulate multiple important biological processes including host antiviral immune response. However, whether NONO can inhibit porcine reproductive and respiratory syndrome virus (PRRSV) replication is less well understood. In this study, we demonstrated that swine NONO (sNONO) inhibited PRRSV replication, via increasing expression of IFN-β, whereas NONO knockdown or knockout in PAM-KNU cells was more susceptible to PRRSV infection. As an IRF3 positive regulation factor, NONO promoted IFN-β expression by enhancing activation of IRF3. During PRRSV infection, NONO further up-regulated IRF3-mediated IFN-β expression by interacting with PRRSV N protein. Mechanistically, NONO functioned as a scaffold protein to detect PRRSV N protein and formed N-NONO-IRF3 complex in the nucleus. Interestingly, it was found that the NONO protein reversed the inhibitory effect of PRRSV N protein on type I IFN signaling pathway. Taken together, our study provides a novel mechanism for NONO to increase the IRF3-mediated IFN-β activation by interacting with the viral N protein to inhibit PRRSV infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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83. Medical-grade honey has superior antibacterial properties against common bacterial isolates in wound cultures of dogs and cats in comparison to non-medical-grade honey types.
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Neo R, Gaonkar P, Huber L, and Hlusko KC
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Objective: To compare the antibacterial activities of different types of honey against common bacterial isolates cultured from wounds of dogs and cats., Methods: 4 types of honey were used including a medical-grade manuka honey, a non-medical-grade manuka honey, a locally sourced non-medical-grade honey (non-MGH), and a commercially sourced non-MGH. Bacterial isolates were obtained from clinical wound cultures of dogs and cats including Staphylococcus pseudintermedius, Escherichia coli, Enterococcus faecalis, and Pseudomonas aeruginosa. The macro-broth dilution method was used to analyze the MIC and minimum bactericidal concentration. The percentage of growth inhibition was assessed for different types of honey at different concentrations using a generalized linear regression model., Results: Medical-grade honey exhibited the lowest minimum bactericidal concentration against S pseudintermedius, E faecalis, and P aeruginosa, alongside the lowest MIC at 90% with statistically significant higher bacterial growth inhibition in medium and low concentrations. Non-medical-grade manuka honey had a similar bactericidal activity against S pseudintermedius and P aeruginosa compared to locally and commercially sourced non-MGH., Conclusions: In this in vitro study, MGH exhibited superior antibacterial activity against all bacterial isolates compared to other types of honey., Clinical Relevance: Medical-grade honey displayed the greatest antibacterial activity against common wound pathogens and could be considered over other types of honey for wound management in cats and dogs. Locally and commercially sourced non-MGH appears to have a comparative efficacy against certain bacteria compared to non-medical-grade manuka honey and is more cost effective. Further in vivo studies are needed to confirm these findings.
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- 2024
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84. Overcoming Irinotecan Resistance by Targeting Its Downstream Signaling Pathways in Colon Cancer.
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Saurav S, Karfa S, Vu T, Liu Z, Datta A, Manne U, Samuel T, and Datta PK
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Among the most popular chemotherapeutic agents, irinotecan, regarded as a prodrug belonging to the camptothecin family that inhibits topoisomerase I, is widely used to treat metastatic colorectal cancer (CRC). Although immunotherapy is promising for several cancer types, only microsatellite-instable (~7%) and not microsatellite-stable CRCs are responsive to it. Therefore, it is important to investigate the mechanism of irinotecan function to identify cellular proteins and/or pathways that could be targeted for combination therapy. Here, we have determined the effect of irinotecan treatment on the expression/activation of tumor suppressor genes (including p15
Ink4b , p21Cip1 , p27Kip1 , and p53) and oncogenes (including OPN, IL8, PD-L1, NF-κB, ISG15, Cyclin D1, and c-Myc) using qRT-PCR, Western blotting, immunofluorescence (IF), and RNA sequencing of tumor specimens. We employed stable knockdown, neutralizing antibodies (Abs), and inhibitors of OPN, p53, and NF-κB to establish downstream signaling and sensitivity/resistance to the cytotoxic activities of irinotecan. Suppression of secretory OPN and NF-κB sensitized colon cancer cells to irinotecan. p53 inhibition or knockdown was not sufficient to block or potentiate SN38-regulated signaling, suggesting p53-independent effects. Irinotecan treatment inhibited tumor growth in syngeneic mice. Analyses of allograft tumors from irinotecan-treated mice validated the cell culture results. RNA-seq data suggested that irinotecan-mediated activation of NF-κB signaling modulated immune and inflammatory genes in mice, which may compromise drug efficacy and promote resistance. In sum, these results suggest that, for CRCs, targeting OPN, NF-κB, PD-L1, and/or ISG15 signaling may provide a potential strategy to overcome resistance to irinotecan-based chemotherapy.- Published
- 2024
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85. Comparative Analysis of Hepatic Gene Expression Profiles in Murine and Porcine Sepsis Models.
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Halimi F, Vanderhaeghen T, Timmermans S, Croubels S, Libert C, and Vandewalle J
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- Animals, Swine, Mice, Gene Expression Profiling, Male, Mice, Inbred C57BL, Sepsis genetics, Sepsis metabolism, Disease Models, Animal, Liver metabolism, Transcriptome, Lipopolysaccharides
- Abstract
Sepsis remains a huge unmet medical need for which no approved drugs, besides antibiotics, are on the market. Despite the clinical impact of sepsis, its molecular mechanism remains inadequately understood. Recent insights have shown that profound hepatic transcriptional reprogramming, leading to fatal metabolic abnormalities, might open a new avenue to treat sepsis. Translation of experimental results from rodents to larger animal models of higher relevance for human physiology, such as pigs, is critical and needs exploration. We performed a comparative analysis of the transcriptome profiles in murine and porcine livers using the following sepsis models: cecal ligation and puncture (CLP) in mice and fecal instillation (FI) in pigs, both of which induce polymicrobial septic peritonitis, and lipopolysaccharide (LPS)-induced endotoxemia in pigs, inducing sterile inflammation. Using bulk RNA sequencing, Metascape pathway analysis, and HOMER transcription factor motif analysis, we were able to identify key genes and pathways affected in septic livers. Conserved upregulated pathways in murine CLP and porcine LPS and FI generally comprise typical inflammatory pathways, except for ER stress, which was only found in the murine CLP model. Conserved pathways downregulated in sepsis comprise almost exclusively metabolic pathways such as monocarboxylic acid, steroid, biological oxidation, and small-molecule catabolism. Even though the upregulated inflammatory pathways were equally induced in the two porcine models, the porcine FI model more closely resembles the metabolic dysfunction observed in the CLP liver compared to the porcine LPS model. This comprehensive comparison focusing on the hepatic responses in mouse CLP versus LPS or FI in pigs shows that the two porcine sepsis models generally resemble quite well the mouse CLP model, with a typical inflammatory signature amongst the upregulated genes and metabolic dysfunction amongst the downregulated genes. The hepatic ER stress observed in the murine model could not be replicated in the porcine models. When studying metabolic dysfunction in the liver upon sepsis, the porcine FI model more closely resembles the mouse CLP model compared to the porcine LPS model.
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- 2024
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86. Ameliorative effects of Akkermansia muciniphila on anxiety-like behavior and cognitive deficits in a rat model of Alzheimer's disease.
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Maftoon H, Davar Siadat S, Tarashi S, Soroush E, Basir Asefi M, Rahimi Foroushani A, and Mehdi Soltan Dallal M
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Alzheimer's Disease (AD) is the primary neurodegenerative disorder in the elderly, lacking a definitive treatment. The gut microbiota influences the gut-brain axis by aiding in hypothalamic-pituitary-adrenal (HPA) axis development and neuromodulator production. Research links AD and gut microbiota, suggesting gut microbiota regulation could be a therapeutic approach for AD. This study explores Akkermansia muciniphila's impact on preventing AD. This research investigates the effect of A. muciniphila consumption (1 × 10
9 CFU) on tau protein-induced AD rats compared to a control group. Rats were divided into four groups: sham, sham + Akk, AD (tau-induced rats), and AD + Akk (tau-induced rats treated with A. muciniphila). A. muciniphila gavage lasted five weeks. Rats underwent qRT-PCR analysis to assess mRNA expression of pro-inflammatory factors (TNF-α, IL-6, IL-1β, IFN-γ) in the hippocampus. Behavioral tests included Morris Water Maze (MWM), Passive Avoidance Memory Test (Shuttle box), Elevated Plus Maze (EPM), and marble burying. After five weeks of A. muciniphila treatment, anxiety-like behavior significantly decreased. The AD group receiving A. muciniphila showed improved spatial and recognition memory compared to the AD group. Pro-inflammatory cytokine levels (TNF-α, IL-1β, IL-6, IFN-γ) decreased. A. muciniphila effectively reduces cognitive impairments and anxiety-related behavior, showing promise as an AD therapeutic by influencing the gut-brain axis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)- Published
- 2024
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87. Endocrine Diagnostics: Principles and Applications.
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Petroff BK, Eustace R, Thompson KA, Kozlowski C, and Agnew D
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Endocrine diagnostics currently depend on the ability to measure low and high concentrations of diagnostic hormones using immunoassays. This often is challenging in species other than humans, dogs, cats, and horses due to lack of validated assays and reference intervals. There are strategies to approach endocrine testing in zoo, wildlife, and zoologic companion animals but caution is needed in interpreting results. Newer techniques such as liquid chromatography-tandem mass spectrometry (LC-MS/MS) may be more useful for all species, although technical hurdles remain for this method too., Competing Interests: Disclosure Drs D. Agnew and B.K. Petroff are employed by Michigan State University Veterinary Diagnostic Laboratory, which performs endocrine testing in animals., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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88. West Nile virus in adults and larvae of Culiseta longiareolata and Culex hortensis (Diptera: Culicidae) captured in Hamedan, western Iran.
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Khaledian M, Owliaee I, Sazmand A, Davari B, Zahirnia AH, and Jalilian FA
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West Nile virus (WNV) is an emerging arbovirus transmitted by mosquitoes. Although it is considered the most widespread mosquito-borne arbovirus in Iran, vectors of this zoonotic pathogen remain unknown in many regions. This study aimed to assess the presence of WNV in mosquitoes collected in the western city of Hamedan in 2022. Adult mosquitoes were captured using light traps, and mosquito larvae were collected by dipping technique from 45 diverse habitats, including urban, suburban, and rural sites. Specimens were identified and pooled into 69 batches based on their species for viral RNA extraction and Real-Time PCR. In total, 3243 mosquitoes (2209 larvae and 1034 adults) were captured and identified as Culiseta longiareolata, Culex hortensis, Anopheles maculipennis s.l., Culex theileri, Culex pipiens, Anopheles claviger, and Anopheles superpictus s.l. in decreasing order. Molecular screening revealed seven WNV-positive pools of Culiseta longiareolata and Culex hortensis in rural (n = 5) and urban areas (n = 2). Detection of WNV RNA indicates active circulation in mosquitoes and risk of transmission to humans and animals in Hamadan. These findings identify putative vectors in Hamadan, though vectors likely vary regionally in Iran. Further surveillance is needed to elucidate local WNV epidemiology and transmission dynamics fully. Nonetheless, this study provides important baseline evidence of WNV activity to guide prevention strategies in this area., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alireza Sazmand is editorial board member of Acta Tropica. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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89. Nephroprotective and hepatoprotective effects of lemongrass essential oil and citral on diclofenac-induced toxicity in mice.
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Tabari MA, Houshyar M, Araghi A, Mirzakhani N, Crescenzo G, Cardone R, and Zizzadoro C
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The present study was carried out to evaluate and compare the protective potential of two well-known antioxidants of herbal origin in a mouse model of acute DIC-induced nephro- and hepatotoxicity. The tested antioxidants included lemongrass essential oil (LO) and its predominant bioactive constituent citral (CIT). A third herbal product, silymarin (SILY), was used as a reference hepato-renal protective agent. DIC administration led to elevated serum urea and creatinine levels, and prompted oxidative stress along with histopathological changes in the kidney tissue. In parallel, DIC administration increased serum liver enzyme activity, decreased total protein, albumin, and globulin levels, and caused oxidative stress with associated histopathological changes in the liver tissue. Pre-treatment with LO or CIT mitigated DIC-induced alterations in all serum biochemical markers of kidney and liver health (except albumin). High-dose LO, like SILY, within kidney and liver tissues, counteracted DIC-induced oxidative stress and histomorphological alterations. By contrast, CIT failed to mitigate DIC-induced oxidative stress in the kidneys and provided only partial control of DIC-induced oxidative stress in the liver, resulting in less efficient preservation of kidney function and liver structural integrity than LO. Besides confirming the efficacy of SILY at protecting kidneys and liver against the toxicity of DIC in a rodent species different from the one tested so far (rat), this study demonstrated the preventive properties of LO and, to a lesser extent, of CIT against DIC-induced hepato-renal toxicity in mice, supporting their developmental potential as therapeutics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
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- 2024
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90. Aflatoxins and fumonisins co-contamination effects on laying hens and use of mycotoxin detoxifiers as a mitigation strategy.
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Ochieng PE, Kemboi DC, Okoth S, De Baere S, Cavalier E, Kang'ethe E, Doupovec B, Gathumbi J, Scippo ML, Antonissen G, Lindahl JF, and Croubels S
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This study examined the effects of fumonisins (FBs) and aflatoxin B1 (AFB1), alone or in combination, on the productivity and health of laying hens, as well as the transfer of aflatoxins (AFs) to chicken food products. The efficacy and safety of mycotoxin detoxifiers (bentonite and fumonisin esterase) to mitigate these effects were also assessed. Laying hens (400) were divided into 20 groups and fed a control, moderate (54.6 µg/kg feed) or high (546 µg/kg feed) AFB1 or FBs (7.9 mg/kg feed) added diets, either alone or in combination, with the mycotoxin detoxifiers added in selected diets. Productivity was evaluated by feed intake, egg weight, egg production, and feed conversion ratio whereas health was assessed by organ weights, blood biochemistry, and mortality. Aflatoxins residues in plasma, liver, muscle, and eggs were determined using UHPLC-MS/MS methods. A diet with AFB1 at a concentration of 546 µg/kg feed decreased egg production and various AFB1-contaminated diets increased serum uric acid levels and weights of liver, spleen, heart, and gizzard. Interactions between AFB1 and FBs significantly impacted spleen, heart, and gizzard weights as well as AFB1 residues in eggs. Maximum AFB1 residues of 0.64 µg/kg and aflatoxin M1 (below limits of quantification) were observed in liver, plasma, and eggs of layers fed diets with AFB1. The mycotoxin detoxifiers reduced effects of AFB1 and FBs on egg production, organ weights, blood biochemistry, and AFB1 residues in tissues. This study highlights the importance of mycotoxin detoxifiers as a mitigation strategy against mycotoxins in poultry production., (© 2024. The Author(s).)
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- 2024
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91. Clinical Manifestations and Molecular Identification of Giardia duodenalis in Pediatric and Adolescent Cancer Patients in Southwestern Iran.
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Mahdavi F, Mohammadi MR, Karimi K, Shamsi L, Maleki F, Asghari A, Shahabi S, Motazedian MH, and Nourmohammadi H
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This study aimed to investigate the clinical and molecular characteristics of Giardia duodenalis ( G. duodenalis ) infection and identify potential risk factors in children and teenagers with malignancies in Shiraz, southwestern Iran. A total of 200 fresh fecal samples were collected from children and adolescents suffering from 32 different cancer types at Amir, Nemazee, and Saadi hospitals affiliated with Shiraz University of Medical Sciences between October 2021 and May 2022. Direct microscopy using saline and iodine wet mount was conducted, and all fecal samples were rechecked by SSU -PCR. Subsequently, a specific fragment of the tpi gene was amplified on all samples for prevalence, sequencing, and assemblage identification. Our study found a 4% (8/200) prevalence of G. duodenalis using microscopy and PCR. The molecular findings were consistent with the microscopic results. All eight positive samples with SSU-rRNA gene were also detected as positive with tpi gene and were correctly sequenced. Among the examined cancer patients, two assemblages were identified: A [sub-assemblage AI (2/8, 25%) and sub-assemblage AII (3/8, 37.5%)] and B [sub-assemblage BIV (3/8, 37.5%)]. Notably, patients were more vulnerable to G. duodenalis infection after receiving at least 8 treatment episodes ( p < 0.05) and displaying gastrointestinal symptoms ( p > 0.05). The demographic characteristics of cancer patients with G. duodenalis infection and the statistical conclusions were separately detailed. The small sample size and low prevalence rate in this study hindered precise epidemiological conclusions. Nonetheless, the results suggest that G. duodenalis infection among cancer patients in Shiraz city originates from humans, without any specific animal groups (C-H) involved.
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- 2024
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92. Herd-level occurrence and risk factors associated with respiratory and enteric pathogens from dairy calves in Ontario: A cross-sectional study.
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Sedó SGU, Winder CB, Perry KV, Caswell JL, Mee JF, MacNicol J, and Renaud DL
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This cross-sectional herd-level study aimed to determine the occurrence of and risk factors for pathogens associated with neonatal calf diarrhea and bovine respiratory disease on Ontario dairy farms. From April to August 2022, a convenience sample of 100 dairy farms were visited once. A questionnaire covering farm biosecurity, calving and colostrum management, preweaning nutrition, and housing was administered on-farm. At each farm visit, approximately 5 calves between 2 and 35 d old were randomly selected for fecal sampling. Furthermore, approximately 5 calves between 21 to 122 d old were randomly selected for nasopharyngeal sampling. In total, 363 fecal samples (from 83 dairy farms) and 390 nasopharyngeal swab samples (from 80 dairy farms) were collected. Fecal samples were analyzed individually using a multiplex PCR to identify bacterial and parasitic enteric pathogens. Nasopharyngeal swabs were analyzed as one pooled sample per farm using bacterial culture and real-time PCR. The most common enteric pathogens detected at herd-level were Cryptosporidium parvum (67.4%) and Escherichia coli K99+ (13.2%). The most common respiratory pathogens detected at herd-level were Pasteurella multocida (62.5%), bovine coronavirus (42.5%), and Mycoplasma bovis (21.2%). Multivariable logistic models were built to explore associations between the most common pathogens and herd-level predictors selected from the questionnaire. Herd positivity for C. parvum was positively associated with having more than 61 preweaned calves per year and feeding mainly whole milk to calves. The presence of M. bovis was positively associated with herds that combined manual and automatic milk-feeding systems, and the presence of bovine coronavirus was positively associated with having more than 98 preweaned calves during the year. Univariable Poisson regression models were built to explore the association between the most common pathogens and preweaning calf mortality. Herds that were positive for C. parvum, M. bovis, or bovine coronavirus had a greater risk of preweaning calf mortality. These results provide insights for future research on pathogens associated with NCD and BRD and offer guidance for veterinarians and dairy farmers in implementing disease control measures in dairy calf herds., (© 2025, The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)
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- 2024
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93. Inter-laboratory comparison of real-time quaking-induced conversion (RT-QuIC) for the detection of chronic wasting disease prions in white-tailed deer retropharyngeal lymph nodes.
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Darish JR, Kaganer AW, Hanley BJ, Schuler KL, Schwabenlander MD, Wolf TM, Ahmed MS, Rowden GR, Larsen PA, Kobashigawa E, Tewari D, Lichtenberg S, Pedersen JA, Zhang S, and Sreevatsan S
- Abstract
The rapid geographic spread of chronic wasting disease (CWD) in white-tailed deer (WTD; Odocoileus virginianus ) increases the need for the development and validation of new detection tests. Real-time quaking-induced conversion (RT-QuIC) has emerged as a sensitive tool for CWD prion detection, but federal approval in the United States has been challenged by practical constraints on validation and uncertainty surrounding RT-QuIC robustness between laboratories. To evaluate the effect of inter-laboratory variation on CWD prion detection using RT-QuIC, we conducted a multi-institution comparison on a shared anonymized sample set. We hypothesized that RT-QuIC can accurately and reliably detect the prions that cause CWD in postmortem samples from medial retropharyngeal lymph node (RPLN) tissue despite variation in laboratory protocols. Laboratories from 6 U.S. states (Michigan, Minnesota, Missouri, New York, Pennsylvania, Wisconsin) were enlisted to compare the use of RT-QuIC in determining CWD prion status (positive or negative) among 50 anonymized RPLNs of known prion status. Our sample set included animals of 3 codon 96 WTD genotypes known to affect CWD progression and detection (G96G, G96S, S96S). All 6 laboratories successfully identified the true disease status consistently for all 3 tested codon 96 genotypes. Our results indicate that RT-QuIC is a suitable test for the detection of CWD prions in RPLN tissues in several genotypes of WTD., Competing Interests: Declaration of conflicting interestsMarc D. Schwabenlander and Peter A. Larsen are co-founders and stock owners, and Gage R. Rowden is a stock owner, of Priogen, a diagnostic company specializing in the ultra-sensitive detection of pathogenic proteins associated with prion and protein-misfolding diseases. The University of Minnesota licensed patent applications to Priogen. None of the other authors declared a competing interest.
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- 2024
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94. Enhancing agricultural sustainability through optimization of the slaughterhouse sludge compost for elimination of parasites and coliforms.
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Rizwan HM, Naveed M, Sajid MS, Nazish N, Younus M, Raza M, Maqbool M, Khalil MH, Fouad D, and Ataya FS
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- Animals, Agriculture methods, Temperature, Hydrogen-Ion Concentration, Humidity, Feces microbiology, Feces parasitology, Parasites, Sewage parasitology, Sewage microbiology, Composting methods, Enterobacteriaceae isolation & purification, Abattoirs
- Abstract
For a sustainable ecology, slaughterhouse sludge must be managed effectively in preview of the parasitic or coliforms' spill over to the community. In order to determine the effectiveness of a customized biological decomposer solution in lowering the parasitic eggs and coliform bacteria, three composting units (Unit 1, Unit 2, and Unit 3) were treated with its different amounts. Over a period of 60 days, pH, temperature, humidity, number of the parasitic eggs per gram (EPG) of faecal material, viability of eggs, and coliform counts were evaluated. By the fifth day of the composting process, pH had significantly (P < 0.05) increased across all the treatments and then decreased gradually. Also on the 5th day, all three units entered the thermophilic range (> 45 °C), which persisted for 20 days for Unit 3 and 15 days for Units 1 and 2. Humidity levels initially increased significantly (P < 0.05) in all three units (Unit 3 = 71%, Unit 2 = 64%, and Unit 1 = 55%) but then gradually decreased. On day 5, no decrease in EPG in Unit 1 was detected; however, a non-significant (P > 0.05) 12.5% decline in EPG in Unit 2 and Unit 3 was recorded. After that, a significant (P < 0.05) reduction in EPG was observed in all the three treatments until day 25. By day 5, decreased egg viability was significantly (P < 0.05) recorded in Unit 3 (21.43%); in Unit 1 and Unit 2, the decrease was 6.25% and 14.29%, respectively. Additionally, all units showed a significant (P < 0.05) decrease in total coliforms, meeting minimum allowable limit in Unit 2 and 3 on day 10 and on day 15 in Unit 1. The most substantial reduction in faecal coliforms was observed in Unit 3 (from 2.6 log₁₀ to 1.3 log₁₀), followed by Unit 2 (from 2.6 log₁₀ to 1.5 log₁₀), and then Unit 1 (from 2.6 log₁₀ to 1.6 log₁₀). The results of this study support recommendation of advanced composting techniques to eradicate or reduce the abundance of pathogens (parasites and coliforms). Hence, we endorse the value of careful composting procedures in environment-friendly abattoir waste management and agricultural practices through creating pathogen-free, eco-friendly fertilizers to promote both agricultural and environmental sustainability., (© 2024. The Author(s).)
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- 2024
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95. Identification, charectrization and genetic transformation of lignin and pectin polysaccharides through CRISPR/Cas9 in Nicotiana tobacum.
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Ahmed RI, Ren A, Alshaya DS, Fiaz S, Kong Y, Liaqat S, Ali N, Saddique MAB, Attia KA, and Taga MUH
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- Gene Editing methods, Transformation, Genetic, Plants, Genetically Modified genetics, Lignin metabolism, Lignin biosynthesis, Nicotiana genetics, Nicotiana metabolism, CRISPR-Cas Systems, Pectins metabolism, Pectins genetics
- Abstract
CRISPR/Cas9 system has been successfully implemented in animals and plants is a second-generation genome editing tool. We are able to optimize a Cas9 system to edited Ntab06050 and Ntab0857410 genes in HD and K326 tobacco cultivars respectively. The gene Ntab06050 is related to lignin synthesis while the gene Ntab0857410 belongs to pectin synthesis by utilizing Agrobacterium-mediated leaf disc method. We have constructed total eight different constructs for the lignin related gene family CCoAMT, out of which three constructs have been selected from Ntab0184090, two constructs from Ntab0392460 while one construct from each Ntab0540120, Ntab0857410 and Ntab0135940 gene. To study the Cas9 system in pectin related genes, total five constructs have been utilized under Cas9 system and multiple target sites were selected by identifying PAM sequences. Out of which three constructs were targeted from NtabGAE1and NtabGAE6 homologous while two were targeted from NtabGAUT4 homologous. Where as, UDP-D-glucuronate 4-epimerase gene family is a Golgi localized, might have a role in the interconvertion of UDP-D-GlcA and UDP-D-GalA in pectin synthesis. We have succeeded in the mutation of pectin related NtabGAUT4 and lignin related NtabCCoAMT genes with 6.2% and 9.4% mutation frequency., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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96. Evaluation of the Anti-Inflammatory/Immunomodulatory Effect of Teucrium montanum L. Extract in Collagen-Induced Arthritis in Rats.
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Bufan B, Marčetić M, Djuretić J, Ćuruvija I, Blagojević V, Božić DD, Milutinović V, Janković R, Sopta J, Kotur-Stevuljević J, and Arsenović-Ranin N
- Abstract
The anti-inflammatory/immunomodulatory effects of Teucrium montanum L. (TM), a plant distributed in the Mediterranean region, have been insufficiently examined. The effects of the TM ethanol extract were tested in a rat collagen-induced arthritis (CIA) model of rheumatoid arthritis. LC-MS was used for the phytochemical analysis of the TM extract. Dark Agouti rats were immunized with bovine type II collagen (CII) in incomplete Freund's adjuvant for CIA, and treated with 100 or 200 mg/kg of TM extract daily via oral administration. Clinical and histopathological evaluations and a flow cytometric analysis of the phenotypic and functional characteristics of splenocytes and draining lymph node cells were performed. The cytokines in the paw tissue culture supernatants and anti-CII antibodies in serum were determined by ELISA. The TM extract, with the dominant components verbascoside and luteolin 7- O -rutinoside, reduced the arthritic score and ankle joint inflammation in CIA rats, promoted the antioxidant profile in serum, and lowered pro-inflammatory TNF-α, IL-6 and IL-1β production. It suppressed the activation status of CD11b+ cells by lowering CD86, MHCII and TLR-4 expression, and promoted the Th17/T regulatory cell (Tregs) balance towards Tregs. A lower frequency of B cells was accompanied by a lower level of anti-CII antibodies in treated rats. These findings imply the favorable effect of TM extract on the clinical presentation of CIA, suggesting its anti-inflammatory/immunomodulatory action and potential therapeutic effect.
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- 2024
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97. Silk fibroin/chitosan thiourea hydrogel scaffold with vancomycin and quercetin-loaded PLGA nanoparticles for treating chronic MRSA osteomyelitis in rats.
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Jafarbeglou M, Meimandi-Parizi A, Derakhshandeh A, Khodakaram-Tafti A, Bigham-Sadegh A, Arkan P, and Jafarbeglou M
- Abstract
Chronic osteomyelitis presents significant treatment challenges, necessitating an efficient system for infection elimination and bone repair. This study developed a natural hydrogel scaffold using silk fibroin (SF) and chitosan thiourea (CST), incorporating vancomycin (VC) and quercetin (QC) loaded PLGA nanoparticles (NPs) for dual-purpose treatment. SF/CST hydrogel scaffolds exhibited homogeneous porosity and smaller interconnected pore size than pure SF and pure CST hydrogel scaffolds. Optimal PLGA/QC NPs measured 206 nm in size, displayed spherical morphology, had uniform distribution, and achieved 87 % QC loading. The release study showed sustained long-term release of VC and QC from the hydrogel scaffolds for over 20 days. Biocompatibility tests indicated that hydrogel scaffolds promoted osteoblast adhesion without cytotoxicity, with QC-containing scaffolds enhancing osteoblast growth. Antibacterial tests confirmed retained VC activity against methicillin-resistant Staphylococcus aureus (MRSA) in SF/CST. An experimental study assessed the efficacy of the hydrogel scaffolds in a MRSA-infected rat osteomyelitis model. Radiographic scores demonstrated a significant reduction for SF/CST-VC-PLGA/QC NPs compared to control, indicating reduced osteomyelitis effects. Macroscopic evaluations showed notable reductions in gross pathological effects for VC-containing groups. Histopathological assessments revealed significantly lower osteomyelitis scores and higher healing scores in the SF/CST-VC-PLGA/QC NPs, with reduced inflammatory cell infiltration and more organized connective tissue formation. In conclusion, SF/CST-VC-PLGA/QC NPs is an effective dual drug delivery system for osteomyelitis treatment, demonstrating significant antibacterial activity, enhanced bone regeneration, and reduced infection rate., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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98. Evaluation of potential novel biomarkers for feline hypertrophic cardiomyopathy.
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Chong A, Joshua J, Raheb S, Pires A, Colpitts M, Caswell JL, and Fonfara S
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Hypertrophic cardiomyopathy (HCM) is the most common cardiomyopathy in cats. The diagnosis can be difficult, requiring advanced echocardiographic skills. Additionally, circulating biomarkers (N-terminal pro-B type natriuretic peptide and cardiac troponin I) have several limitations when used for HCM screening. In previous work, we identified interleukin 18 (IL-18), insulin-like growth factor binding protein 2 (IGFBP-2), brain-type glycogen phosphorylase B (PYGB), and WNT Family Member 5 A (WNT5A) as myocardial genes that show significant differential expression between cats with HCM and healthy cats. The products of these genes are released into the circulation, and we hypothesized that IL-18, IGFBP-2, PYGB, and WNT5A serum RNA and protein concentrations differ between healthy cats, cats with subclinical HCM, and those with HCM and congestive heart failure (HCM + CHF). Reverse transcriptase quantitative polymerase chain reaction (RTqPCR) and enzyme-linked immunosorbent assay (ELISA) were applied to evaluate gene and protein expression, respectively, in the serum of eight healthy controls, eight cats with subclinical HCM, and six cats with HCM + CHF. Serum IGFBP-2 RNA concentrations were significantly different among groups and were highest in cats with subclinical HCM. Compared to healthy controls, serum IL-18 and WNT5A gene expression were significantly higher in cats with HCM + CHF, and WNT5A was higher in cats with subclinical HCM. No differences were observed for PYGB. These results indicate that further investigation via large scale clinical studies for IGFBP-2, WNT5A, and IL-18 may be valuable in diagnosing and staging feline HCM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)
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- 2024
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99. Pediatric Eyelid Cutaneous Horns: A Case Series and Literature Review.
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Barbara R, Abdelaal AM, Levy R, Nagy A, Mireskandari K, and Ali A
- Abstract
Purpose: To describe the clinical and histopathologic features of pediatric eyelid cutaneous horns., Design: Retrospective observational case series and review of literature., Subjects: Five pediatric patients with eyelid cutaneous horns Methods: Five cases with eyelid cutaneous horns were retrospectively identified using departmental databases. Patients' records were analyzed for demographic data, clinical appearance, histologic findings, and clinical course. An excisional biopsy of the lesion was performed in 3 patients. The remaining 2 patients were managed conservatively., Main Outcome Measures: Clinical outcome and histopathologic evaluation with emphasis on excluding malignancy., Results: All 5 cutaneous horn lesions resolved surgically or conservatively. The average age at presentation was 6.6 years (range 5-11 years). Clinically, 4 lesions were preceded by a hordeolum or chalazion and all excised lesions had benign features on histologic examination. Mitotic figures or atypia were not observed. None of the patients developed recurrence during the follow-up period ranging from 1 to 96 months. Five previous reports of five cases were found on review of the literature. Our case series doubles this number to support the benign nature of these lesions in children., Conclusions: Pediatric eyelid cutaneous horns are closely related to eyelid margin inflammatory disease and appear to follow a benign course. This contrasts with the adult population where cutaneous horns are frequently associated with neoplasia., (Copyright © 2024. Published by Elsevier Inc.)
- Published
- 2024
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100. Paneth cell TNF signaling induces gut bacterial translocation and sepsis.
- Author
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Wallaeys C, Garcia-Gonzalez N, Timmermans S, Vandewalle J, Vanderhaeghen T, De Beul S, Dufoor H, Eggermont M, Moens E, Bosteels V, De Rycke R, Thery F, Impens F, Verbanck S, Lienenklaus S, Janssens S, Blumberg RS, Iwawaki T, and Libert C
- Subjects
- Animals, Mice, Unfolded Protein Response, Mice, Inbred C57BL, Mice, Knockout, Endoribonucleases metabolism, Endoribonucleases genetics, Protein Serine-Threonine Kinases metabolism, Antimicrobial Peptides metabolism, Paneth Cells metabolism, Sepsis microbiology, Bacterial Translocation, Signal Transduction, Tumor Necrosis Factor-alpha metabolism
- Abstract
The cytokine tumor necrosis factor (TNF) plays important roles in limiting infection but is also linked to sepsis. The mechanisms underlying these paradoxical roles are unclear. Here, we show that TNF limits the antimicrobial activity of Paneth cells (PCs), causing bacterial translocation from the gut to various organs. This TNF-induced lethality does not occur in mice with a PC-specific deletion in the TNF receptor, P55. In PCs, TNF stimulates the IFN pathway and ablates the steady-state unfolded protein response (UPR), effects not observed in mice lacking P55 or IFNAR1. TNF triggers the transcriptional downregulation of IRE1 key genes Ern1 and Ern2, which are key mediators of the UPR. This UPR deficiency causes a significant reduction in antimicrobial peptide production and PC antimicrobial activity, causing bacterial translocation to organs and subsequent polymicrobial sepsis, organ failure, and death. This study highlights the roles of PCs in bacterial control and therapeutic targets for sepsis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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