المؤلفون: Augustijn, Kevin D., Duval, Dawn L., Wechselberger, Rainer, Kaptein, Rob, Gutierrez-Hartmann, Arthur, van der Vliet, Peter C.

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 2002 Oct 01. 99(20), 12657-12662.

الوصول الحر: https://www.jstor.org/stable/3073279Test

المؤلفون: van Swelm, Rachel P. L., Laarakkers, Coby M. M., van der Kuur, Ellen C., Morava-Kozicz, Eva, Wevers, Ron A., Augustijn, Kevin D., Touw, Daan J., Sandel, Maro H., Masereeuw, Rosalinde, Russel, Frans G. M.

المصدر: van Swelm , R P L , Laarakkers , C M M , van der Kuur , E C , Morava-Kozicz , E , Wevers , R A , Augustijn , K D , Touw , D J , Sandel , M H , Masereeuw , R & Russel , F G M 2012 , ' Identification of Novel Translational Urinary Biomarkers for Acetaminophen-Induced Acute Liver Injury Using Proteomic Profiling in Mice ' , PLoS ONE , vol. 7 , no. 11 , e49524 . https://doi.org/10.1371/journal.pone.0049524Test

مصطلحات موضوعية: acetylsalicylic acid, alanine aminotransferase, alendronic acid, alprazolam, amoxicillin plus clavulanic acid, biological marker, caffeine, calmodulin, carbonate dehydratase III, copper zinc superoxide dismutase, cotrimoxazole, diazepam, dipyridamole, furosemide, ibuprofen, lercanidipine, metacetamol, metoprolol, omeprazole, pantoprazole, paracetamol, adult, aged, alanine aminotransferase blood level, animal experiment, animal model, article, body weight, controlled study, female

الوصف: Drug-induced liver injury (DILI) is the leading cause of acute liver failure. Currently, no adequate predictive biomarkers for DILI are available. This study describes a translational approach using proteomic profiling for the identification of urinary proteins related to acute liver injury induced by acetaminophen (APAP). Mice were given a single intraperitoneal dose of APAP (0-350 mg/kg bw) followed by 24 h urine collection. Doses of ≥275 mg/kg bw APAP resulted in hepatic centrilobular necrosis and significantly elevated plasma alanine aminotransferase (ALT) values (p

وصف الملف: application/pdf

العلاقة: https://research.rug.nl/en/publications/6a882589-f692-4f57-922d-106799a26757Test

الإتاحة: https://doi.org/10.1371/journal.pone.0049524Test
https://hdl.handle.net/11370/6a882589-f692-4f57-922d-106799a26757Test
https://research.rug.nl/en/publications/6a882589-f692-4f57-922d-106799a26757Test
https://pure.rug.nl/ws/files/48884749/Van_Swelm_2012_Identification_of_novel_translation.pdfTest

المؤلفون: Mota Maria M, Ramesar Jai, Moore Sally G, Augustijn Kevin D, Douradinha Bruno, Waters Andrew P, Janse Chris J, Thompson Joanne

المصدر: Malaria Journal, Vol 10, Iss 1, p 71 (2011)

مصطلحات موضوعية: Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216

الوصف: Background The Plasmodium Cysteine Repeat Modular Proteins (PCRMP) are a family of four conserved proteins of malaria parasites, that contain a number of motifs implicated in host-parasite interactions. Analysis of mutants of the rodent parasite Plasmodium berghei lacking expression of PCRMP1 or 2 showed that these proteins are essential for targeting of P. berghei sporozoites to the mosquito salivary gland and, hence, for transmission from the mosquito to the mouse. Methods In this work, the role of the remaining PCRMP family members, PCRMP3 and 4, has been investigated throughout the Plasmodium life cycle by generation and analysis of P. berghei gene deletion mutants, Δ pcrmp 3 and Δ pcrmp 4. The role of PCRMP members during the transmission and hepatic stages of the Plasmodium lifecycle has been evaluated by light- and electron microscopy and by analysis of liver stage development in HEPG2 cells in vitro and by infecting mice with mutant sporozoites. In addition, mice were immunized with live Δ pcrmp 3 and Δ pcrmp 4 sporozoites to evaluate their immunization potential as a genetically-attenuated parasite-based vaccine. Results Disruption of pcrmp3 and pcrmp4 in P. berghei revealed that they are also essential for transmission of the parasite through the mosquito vector, although acting in a distinct way to pbcrmp1 and 2 . Mutants lacking expression of PCRMP3 or PCRMP4 show normal blood stage development and oocyst formation in the mosquito and develop into morphologically normal sporozoites, but these have a defect in egress from oocysts and do not enter the salivary glands. Sporozoites extracted from oocysts perform gliding motility and invade and infect hepatocytes but do not undergo further development and proliferation. Furthermore, the study shows that immunization with Δ crmp3 and Δ crmp4 sporozoites does not confer protective immunity upon subsequent challenge. Conclusions PCRMP3 and 4 play multiple roles during the Plasmodium life cycle; they are essential for the establishment of sporozoite ...

العلاقة: http://www.malariajournal.com/content/10/1/71Test; https://doaj.org/toc/1475-2875Test; https://doaj.org/article/18a4863b66944a7a8929e887655d829dTest

الإتاحة: https://doi.org/10.1186/1475-2875-10-71Test
https://doaj.org/article/18a4863b66944a7a8929e887655d829dTest

المؤلفون: Douradinha, Bruno, Augustijn, Kevin D, Moore, Sally G, Ramesar, Jai, Mota, Maria M, Waters, Andrew P, Janse, Chris J, Thompson, Joanne

المصدر: Malaria Journal ; volume 10, issue 1 ; ISSN 1475-2875

مصطلحات موضوعية: Infectious Diseases, Parasitology

الوصف: Background The Plasmodium Cysteine Repeat Modular Proteins (PCRMP) are a family of four conserved proteins of malaria parasites, that contain a number of motifs implicated in host-parasite interactions. Analysis of mutants of the rodent parasite Plasmodium berghei lacking expression of PCRMP1 or 2 showed that these proteins are essential for targeting of P. berghei sporozoites to the mosquito salivary gland and, hence, for transmission from the mosquito to the mouse. Methods In this work, the role of the remaining PCRMP family members, PCRMP3 and 4, has been investigated throughout the Plasmodium life cycle by generation and analysis of P. berghei gene deletion mutants, Δ pcrmp 3 and Δ pcrmp 4. The role of PCRMP members during the transmission and hepatic stages of the Plasmodium lifecycle has been evaluated by light- and electron microscopy and by analysis of liver stage development in HEPG2 cells in vitro and by infecting mice with mutant sporozoites. In addition, mice were immunized with live Δ pcrmp 3 and Δ pcrmp 4 sporozoites to evaluate their immunization potential as a genetically-attenuated parasite-based vaccine. Results Disruption of pcrmp3 and pcrmp4 in P. berghei revealed that they are also essential for transmission of the parasite through the mosquito vector, although acting in a distinct way to pbcrmp1 and 2 . Mutants lacking expression of PCRMP3 or PCRMP4 show normal blood stage development and oocyst formation in the mosquito and develop into morphologically normal sporozoites, but these have a defect in egress from oocysts and do not enter the salivary glands. Sporozoites extracted from oocysts perform gliding motility and invade and infect hepatocytes but do not undergo further development and proliferation. Furthermore, the study shows that immunization with Δ crmp3 and Δ crmp4 sporozoites does not confer protective immunity upon subsequent challenge. Conclusions PCRMP3 and 4 play multiple roles during the Plasmodium life cycle; they are essential for the establishment of sporozoite ...

الإتاحة: https://doi.org/10.1186/1475-2875-10-71Test

المؤلفون: Dobson, Sarah E., Augustijn, Kevin D., Brannigan, James A., Schnick, Claudia, Janse, Chris J., Dodson, Eleanor J., Waters, Andrew P., Wilkinson, Anthony J.

المساهمون: Wellcome Trust, The Netherlands Organization for Scientific Research

المصدر: Protein Science ; volume 18, issue 12, page 2578-2591 ; ISSN 0961-8368 1469-896X

الوصف: Malaria, caused by Plasmodium falciparum and related parasites, is responsible for millions of deaths each year, mainly from complications arising from the blood stages of its life cycle. Macrophage migration inhibitory factor (MIF), a protein expressed by the parasite during these stages, has been characterized in mammals as a cytokine involved in a broad spectrum of immune responses. It also possesses two catalytic activities, a tautomerase and an oxidoreductase, though the physiological significance of neither reaction is known. Here, we have determined the crystal structure of MIF from two malaria parasites, Plasmodium falciparum and Plasmodium berghei at 2.2 Å and 1.8 Å, respectively. The structures have an α/β fold and each reveals a trimer, in agreement with the results of analytical ultracentrifugation. We observed open and closed active sites, these being distinguished by movements of proline‐1, the catalytic base in the tautomerase reaction. These states correlate with the covalent modification of cysteine 2 to form a mercaptoethanol adduct, an observation confirmed by mass spectrometry. The Plasmodium MIFs have a different pattern of conserved cysteine residues to the mammalian MIFs and the side chain of Cys58, which is implicated in the oxidoreductase activity, is buried. This observation and the evident redox reactivity of Cys2 suggest quite different oxidoreductase characteristics. Finally, we show in pull‐down assays that Plasmodium MIF binds to the cell surface receptor CD74, a known mammalian MIF receptor implying that parasite MIF has the ability to interfere with, or modulate, host MIF activity through a competitive binding mechanism.

الإتاحة: https://doi.org/10.1002/pro.263Test

المؤلفون: Augustijn, Kevin D., Kleemann, Robert, Thompson, Joanne, Kooistra, Teake, Crawford, Carina E., Reece, Sarah E., Pain, Arnab, Siebum, Arjan H. G., Janse, Chris J., Waters, Andrew P

المصدر: Infection and Immunity ; volume 75, issue 3, page 1116-1128 ; ISSN 0019-9567 1098-5522

الوصف: Macrophage migration inhibitory factor (MIF) is a mammalian cytokine that participates in innate and adaptive immune responses. Homologues of mammalian MIF have been discovered in parasite species infecting mammalian hosts (nematodes and malaria parasites), which suggests that the parasites express MIF to modulate the host immune response upon infection. Here we report the first biochemical and genetic characterization of a Plasmodium MIF ( P MIF). Like human MIF, histidine-tagged purified recombinant P MIF shows tautomerase and oxidoreductase activities (although the activities are reduced compared to those of histidine-tagged human MIF) and efficiently inhibits AP-1 activity in human embryonic kidney cells. Furthermore, we found that Plasmodium berghei MIF is expressed in both a mammalian host and a mosquito vector and that, in blood stages, it is secreted into the infected erythrocytes and released upon schizont rupture. Mutant P. berghei parasites lacking P MIF were able to complete the entire life cycle and exhibited no significant changes in growth characteristics or virulence features during blood stage infection. However, rodent hosts infected with knockout parasites had significantly higher numbers of circulating reticulocytes. Our results suggest that P MIF is produced by the parasite to influence host immune responses and the course of anemia upon infection.

الإتاحة: https://doi.org/10.1128/iai.00902-06Test

المؤلفون: Douradinha, Bruno, Augustijn, Kevin D, Moore, Sally G, Ramesar, Jai, Mota, Maria M, Waters, Andrew P, Janse, Chris J, Thompson, Joanne

الوصف: Background The Plasmodium Cysteine Repeat Modular Proteins (PCRMP) are a family of four conserved proteins of malaria parasites, that contain a number of motifs implicated in host-parasite interactions. Analysis of mutants of the rodent parasite Plasmodium berghei lacking expression of PCRMP1 or 2 showed that these proteins are essential for targeting of P. berghei sporozoites to the mosquito salivary gland and, hence, for transmission from the mosquito to the mouse. Methods In this work, the role of the remaining PCRMP family members, PCRMP3 and 4, has been investigated throughout the Plasmodium life cycle by generation and analysis of P. berghei gene deletion mutants, Δ pcrmp 3 and Δ pcrmp 4. The role of PCRMP members during the transmission and hepatic stages of the Plasmodium lifecycle has been evaluated by light- and electron microscopy and by analysis of liver stage development in HEPG2 cells in vitro and by infecting mice with mutant sporozoites. In addition, mice were immunized with live Δ pcrmp 3 and Δ pcrmp 4 sporozoites to evaluate their immunization potential as a genetically-attenuated parasite-based vaccine. Results Disruption of pcrmp3 and pcrmp4 in P. berghei revealed that they are also essential for transmission of the parasite through the mosquito vector, although acting in a distinct way to pbcrmp1 and 2 . Mutants lacking expression of PCRMP3 or PCRMP4 show normal blood stage development and oocyst formation in the mosquito and develop into morphologically normal sporozoites, but these have a defect in egress from oocysts and do not enter the salivary glands. Sporozoites extracted from oocysts perform gliding motility and invade and infect hepatocytes but do not undergo further development and proliferation. Furthermore, the study shows that immunization with Δ crmp3 and Δ crmp4 sporozoites does not confer protective immunity upon subsequent challenge. Conclusions PCRMP3 and 4 play multiple roles during the Plasmodium life cycle; they are essential for the establishment of sporozoite ...

العلاقة: http://www.malariajournal.com/content/10/1/71Test

الإتاحة: http://www.malariajournal.com/content/10/1/71Test

المؤلفون: Kooij, Taco W.A., Franke-Fayard, Blandine, Renz, Jasper, Kroeze, Hans, van Dooren, Maaike W., Ramesar, Jai, Augustijn, Kevin D., Janse, Chris J., Waters, Andrew P.

المصدر: Molecular and Biochemical Parasitology ; volume 144, issue 1, page 16-26 ; ISSN 0166-6851

مصطلحات موضوعية: Molecular Biology, Parasitology

الإتاحة: https://doi.org/10.1016/j.molbiopara.2005.07.003Test
https://api.elsevier.com/content/article/PII:S0166685105002161?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0166685105002161?httpAccept=text/plainTest

المؤلفون: HENDRIKS-STEGEMAN, BRENDA I., AUGUSTIJN, KEVIN D., BAKKER, BERT, HOLTHUIZEN, PIETERNELLA, VAN DER VLIET, PETER C., JANSEN, MAARTEN

المصدر: Journal of Clinical Endocrinology & Metabolism; Apr 2001, Vol. 86 Issue 4, p1545-1550, 6p, 4 Diagrams, 4 Graphs

المؤلفون: Augustijn, Kevin D., Kleemann, Robert, Thompson, Joanne, Kooistra, Teake, Crawford, Carina E., Reece, Sarah E., Pain, Arnab, Siebum, Arjan H. G., Janse, Chris J., Waters, Andrew P

المصدر: Infection and Immunity; March 2007, Vol. 75 Issue: 3 p1116-1128, 13p

مستخلص: Macrophage migration inhibitory factor (MIF) is a mammalian cytokine that participates in innate and adaptive immune responses. Homologues of mammalian MIF have been discovered in parasite species infecting mammalian hosts (nematodes and malaria parasites), which suggests that the parasites express MIF to modulate the host immune response upon infection. Here we report the first biochemical and genetic characterization of a Plasmodium MIF (PMIF). Like human MIF, histidine-tagged purified recombinant PMIF shows tautomerase and oxidoreductase activities (although the activities are reduced compared to those of histidine-tagged human MIF) and efficiently inhibits AP-1 activity in human embryonic kidney cells. Furthermore, we found that Plasmodium berghei MIF is expressed in both a mammalian host and a mosquito vector and that, in blood stages, it is secreted into the infected erythrocytes and released upon schizont rupture. Mutant P. berghei parasites lacking PMIF were able to complete the entire life cycle and exhibited no significant changes in growth characteristics or virulence features during blood stage infection. However, rodent hosts infected with knockout parasites had significantly higher numbers of circulating reticulocytes. Our results suggest that PMIF is produced by the parasite to influence host immune responses and the course of anemia upon infection.