Journal articles: 'Nagana'

1

Martini, Oberstabsarzt. "Aus der Epidemiologie der Schlafkrankheit und Nagana." Zeitschrift für Angewandte Entomologie 28, no. 2-3 (2009): 488–500. http://dx.doi.org/10.1111/j.1439-0418.1941.tb01037.x.

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Boulanger, Nathalie, Rebecca J. L. Munks, Joanne V. Hamilton, et al. "Epithelial Innate Immunity." Journal of Biological Chemistry 277, no. 51 (2002): 49921–26. http://dx.doi.org/10.1074/jbc.m206296200.

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The gut epithelium is an essential interface in insects that transmit parasites. We investigated the role that local innate immunity might have on vector competence, takingStomoxys calcitransas a model.S. calcitransis sympatric with tsetse flies, feeds on many of the same vertebrate hosts, and is thus regularly exposed to the trypanosomes that cause African sleeping sickness and nagana. Despite this,S. calcitransis not a cyclical vector of these trypanosomes. Trypanosomes develop exclusively in the lumen of digestive organs, and so epithelial immune mechanisms, and in particular antimicrobial peptides (AMPs), may be the prime determinants of the fate of an infection. To investigate whyS. calcitransis not a cyclical vector of trypanosomes, we have looked in its midgut for AMPs with trypanolytic activity. We have identified a new AMP of 42 amino acids, which we named stomoxyn, constitutively expressed and secreted exclusively in the anterior midgut ofS. calcitrans. It displays an amphipathic helical structure and exhibits a broad activity spectrum affecting the growth of microorganisms. Interestingly, this AMP exhibits trypanolytic activity toTrypanosoma brucei rhodesiense. We argue that stomoxyn may help to explain whyS. calcitransis not a vector of trypanosomes causing African sleeping sickness and nagana.

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Authié, Édith, Frédéric Bringaud, Norbert Bakalara, Emmanuel Tetaud, and Théo Baltz. "Trypanosomoses humaines et animales: maladie du sommeil et Nagana." Annales de l'Institut Pasteur / Actualités 10, no. 1 (1999): 27–50. http://dx.doi.org/10.1016/s0924-4204(99)80021-3.

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Cauchard, S., N. Van Reet, P. Büscher, et al. "Killing of Trypanozoon Parasites by the Equine Cathelicidin eCATH1." Antimicrobial Agents and Chemotherapy 60, no. 5 (2016): 2610–19. http://dx.doi.org/10.1128/aac.01127-15.

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ABSTRACTTrypanozoonparasites infect both humans, causing sleeping sickness, and animals, causing nagana, surra, and dourine. Control of nagana and surra depends to a great extent on chemotherapy. However, drug resistance to several of the front-line drugs is rising. Furthermore, there is no official treatment for dourine. Therefore, there is an urgent need to develop antiparasitic agents with novel modes of action. Host defense peptides have recently gained attention as promising candidates. We have previously reported that one such peptide, the equine antimicrobial peptide eCATH1, is highly active against equine Gram-positive and Gram-negative bacteria, without cytotoxicity against mammalian cells at bacteriolytic concentrations. In the present study, we show that eCATH1 exhibits anin vitro50% inhibitory concentration (IC50) of 9.5 μM againstTrypanosoma brucei brucei,Trypanosoma evansi, andTrypanosoma equiperdum. Its trypanocidal mechanism involves plasma membrane permeabilization and mitochondrial alteration based on the following data: (i) eCATH1 induces the rapid influx of the vital dye SYTOX Green; (ii) it rapidly disrupts mitochondrial membrane potential, as revealed by immunofluorescence microscopy using the fluorescent dye rhodamine 123; (iii) it severely damages the membrane and intracellular structures of the parasites as early as 15 min after exposure at 9.5 μM and 5 min after exposure at higher concentrations (19 μM), as evidenced by scanning and transmission electron microscopy. We also demonstrate that administration of eCATH1 at a dose of 10 mg/kg toT. equiperdum-infected mice delays mortality. Taken together, our findings suggest that eCATH1 is an interesting template for the development of novel therapeutic agents in the treatment of trypanosome infections.

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MacLEOD, E. T., I. MAUDLIN, A. C. DARBY, and S. C. WELBURN. "Antioxidants promote establishment of trypanosome infections in tsetse." Parasitology 134, no. 6 (2007): 827–31. http://dx.doi.org/10.1017/s0031182007002247.

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SUMMARYEfficient, cyclical transmission of trypanosomes through tsetse flies is central to maintenance of human sleeping sickness and nagana across sub-Saharan Africa. Infection rates in tsetse are normally very low as most parasites ingested with the fly bloodmeal die in the fly gut, displaying the characteristics of apoptotic cells. Here we show that a range of antioxidants (glutathione, cysteine, N-acetyl-cysteine, ascorbic acid and uric acid), when added to the insect bloodmeal, can dramatically inhibit cell death of Trypanosoma brucei brucei in tsetse. Both L- and D-cysteine invoked similar effects suggesting that inhibition of trypanosome death is not dependent on protein synthesis. The present work suggests that antioxidants reduce the midgut environment protecting trypanosomes from cell death induced by reactive oxygen species.

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Haynes, Carole L. F., Paul Ameloot, Han Remaut, Nico Callewaert, Yann G. J. Sterckx, and Stefan Magez. "Production, purification and crystallization of atrans-sialidase fromTrypanosoma vivax." Acta Crystallographica Section F Structural Biology Communications 71, no. 5 (2015): 577–85. http://dx.doi.org/10.1107/s2053230x15002496.

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Sialidases andtrans-sialidases play important roles in the life cycles of various microorganisms. These enzymes can serve nutritional purposes, act as virulence factors or mediate cellular interactions (cell evasion and invasion). In the case of the protozoan parasiteTrypanosoma vivax,trans-sialidase activity has been suggested to be involved in infection-associated anaemia, which is the major pathology in the disease nagana. The physiological role of trypanosomaltrans-sialidases in host–parasite interaction as well as their structures remain obscure. Here, the production, purification and crystallization of a recombinant version ofT. vivaxtrans-sialidase 1 (rTvTS1) are described. The obtained rTvTS1 crystals diffracted to a resolution of 2.5 Å and belonged to the orthorhombic space groupP212121, with unit-cell parametersa= 57.3,b= 78.4,c= 209.0 Å.

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D'Amico, F., J. M. Poussinga, C. Le Masson, Alain Le Masson, and Dominique Cuisance. "Pratiques pastorales Mbororo et trypanosomoses bovines dans une zone de savanes humides de Centrafrique." Revue d’élevage et de médecine vétérinaire des pays tropicaux 48, no. 2 (1995): 203–12. http://dx.doi.org/10.19182/remvt.9473.

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L'étude a porté sur l'agencement de l'espace pastoral chez les éleveurs Mbororo de Centrafrique et les mouvements de leurs zébus à robe acajou. Outre le campement des éleveurs, cet espace est divisé en trois compartiments principaux : l'aire de repos, l'abreuvoir et le Pâturage sillonné de sentiers. Son utilisation repose sur une ségrégation spatiale et temporelle des déplacements des animaux. Dans le contexte particulier des savanes humides du centre de la République centrafricaine, où l'espèce riveraine Glossina fuscipes fuscipes Newst. 1910 est le vecteur principal des trypanosomoses bovines, les auteurs montrent qu'une connaissance approfondie des pratiques pastorales apporte de nouveaux éléments à la compréhension de l'épidémiologie du nagana. Ainsi, la conduite différentielle des veaux par rapport mix adultes est-elle vraisemblablement un facteur épidémiologique capital.

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8

Cook, G. C. "Sir David Bruce's elucidation of the aetiology of nagana—exactly one hundred years ago." Transactions of the Royal Society of Tropical Medicine and Hygiene 88, no. 3 (1994): 257–58. http://dx.doi.org/10.1016/0035-9203(94)90068-x.

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9

Lorger, Mihaela, Markus Engstler, Matthias Homann, and H. Ulrich Göringer. "Targeting the Variable Surface of African Trypanosomes with Variant Surface Glycoprotein-Specific, Serum-Stable RNA Aptamers." Eukaryotic Cell 2, no. 1 (2003): 84–94. http://dx.doi.org/10.1128/ec.2.1.84-94.2003.

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ABSTRACT African trypanosomes cause sleeping sickness in humans and Nagana in cattle. The parasites multiply in the blood and escape the immune response of the infected host by antigenic variation. Antigenic variation is characterized by a periodic change of the parasite protein surface, which consists of a variant glycoprotein known as variant surface glycoprotein (VSG). Using a SELEX (systematic evolution of ligands by exponential enrichment) approach, we report the selection of small, serum-stable RNAs, so-called aptamers, that bind to VSGs with subnanomolar affinity. The RNAs are able to recognize different VSG variants and bind to the surface of live trypanosomes. Aptamers tethered to an antigenic side group are capable of directing antibodies to the surface of the parasite in vitro. In this manner, the RNAs might provide a new strategy for a therapeutic intervention to fight sleeping sickness.

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Nagamune, Kisaburo, Alvaro Acosta-Serrano, Haruki Uemura, et al. "Surface Sialic Acids Taken from the Host Allow Trypanosome Survival in Tsetse Fly Vectors." Journal of Experimental Medicine 199, no. 10 (2004): 1445–50. http://dx.doi.org/10.1084/jem.20030635.

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The African trypanosome Trypanosoma brucei, which causes sleeping sickness in humans and Nagana disease in livestock, is spread via blood-sucking Tsetse flies. In the fly's intestine, the trypanosomes survive digestive and trypanocidal environments, proliferate, and translocate into the salivary gland, where they become infectious to the next mammalian host. Here, we show that for successful survival in Tsetse flies, the trypanosomes use trans-sialidase to transfer sialic acids that they cannot synthesize from host's glycoconjugates to the glycosylphosphatidylinositols (GPIs), which are abundantly expressed on their surface. Trypanosomes lacking sialic acids due to a defective generation of GPI-anchored trans-sialidase could not survive in the intestine, but regained the ability to survive when sialylated by means of soluble trans-sialidase. Thus, surface sialic acids appear to protect the parasites from the digestive and trypanocidal environments in the midgut of Tsetse flies.

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11

Gumbo, Maureen, Richard Beteck, Tawanda Mandizvo, et al. "Cinnamoyl-Oxaborole Amides: Synthesis and Their in Vitro Biological Activity." Molecules 23, no. 8 (2018): 2038. http://dx.doi.org/10.3390/molecules23082038.

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Due to the increased interest in their application in the treatment of infectious diseases, boron-containing compounds have received a significant coverage in the literature. Herein, a small set of novel cinnamoly-oxaborole amides were synthesized and screened against nagana Trypanosoma brucei brucei for antitrypanosomal activity. Compound 5g emerged as a new hit with an in vitro IC50 value of 0.086 μM against T. b. brucei without obvious inhibitory activity against HeLa cell lines. The same series was also screened against other human pathogens, including Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), for which moderate to weak activity (10 to >125 μM) was observed. Similarly, these compounds exhibited moderate activity against the human protozoal pathogen Trichomonas vaginalis with no observed effect on common microbiome bacterial species. The cross-species inhibitory activity presents the possibility of these compounds serving as broad-spectrum antibiotics for these prevalent three human pathogens.

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12

Magri, Alice, Roberta Galuppi, and Marialetizia Fioravanti. "Autochthonous Trypanosoma spp. in European Mammals: A Brief Journey amongst the Neglected Trypanosomes." Pathogens 10, no. 3 (2021): 334. http://dx.doi.org/10.3390/pathogens10030334.

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The genus Trypanosoma includes flagellated protozoa belonging to the family Trypanosomatidae (Euglenozoa, Kinetoplastida) that can infect humans and several animal species. The most studied species are those causing severe human pathology, such as Chagas disease in South and Central America, and the human African trypanosomiasis (HAT), or infections highly affecting animal health, such as nagana in Africa and surra with a wider geographical distribution. The presence of these Trypanosoma species in Europe has been thus far linked only to travel/immigration history of the human patients or introduction of infected animals. On the contrary, little is known about the epidemiological status of trypanosomes endemically infecting mammals in Europe, such as Trypanosomatheileri in ruminants and Trypanosomalewisi in rodents and other sporadically reported species. This brief review provides an updated collection of scientific data on the presence of autochthonous Trypanosoma spp. in mammals on the European territory, in order to support epidemiological and diagnostic studies on Trypanosomatid parasites.

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Blom-Potar, Marie Christine, Nathalie Chamond, Alain Cosson, et al. "Trypanosoma vivax Infections: Pushing Ahead with Mouse Models for the Study of Nagana. II. Immunobiological Dysfunctions." PLoS Neglected Tropical Diseases 4, no. 8 (2010): e793. http://dx.doi.org/10.1371/journal.pntd.0000793.

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14

Vidilaseris, Keni, Nicolas Landrein, Yulia Pivovarova, et al. "Crystal structure of the N-terminal domain of the trypanosome flagellar protein BILBO1 reveals a ubiquitin fold with a long structured loop for protein binding." Journal of Biological Chemistry 295, no. 6 (2019): 1489–99. http://dx.doi.org/10.1074/jbc.ra119.010768.

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Trypanosoma brucei is a protist parasite causing sleeping sickness and nagana in sub-Saharan Africa. T. brucei has a single flagellum whose base contains a bulblike invagination of the plasma membrane called the flagellar pocket (FP). Around the neck of the FP on its cytoplasmic face is a structure called the flagellar pocket collar (FPC), which is essential for FP biogenesis. BILBO1 was the first characterized component of the FPC in trypanosomes. BILBO1's N-terminal domain (NTD) plays an essential role in T. brucei FPC biogenesis and is thus vital for the parasite's survival. Here, we report a 1.6-Å resolution crystal structure of TbBILBO1-NTD, which revealed a conserved horseshoe-like hydrophobic pocket formed by an unusually long loop. Results from mutagenesis experiments suggested that another FPC protein, FPC4, interacts with TbBILBO1 by mainly contacting its three conserved aromatic residues Trp-71, Tyr-87, and Phe-89 at the center of this pocket. Our findings disclose the binding site of TbFPC4 on TbBILBO1-NTD, which may provide a basis for rational drug design targeting BILBO1 to combat T. brucei infections.

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Panethymitaki, Chrysoula, Paul W. Bowyer, Helen P. Price, Robin J. Leatherbarrow, Katherine A. Brown, and Deborah F. Smith. "Characterization and selective inhibition of myristoyl-CoA:protein N-myristoyltransferase from Trypanosoma brucei and Leishmania major." Biochemical Journal 396, no. 2 (2006): 277–85. http://dx.doi.org/10.1042/bj20051886.

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The eukaryotic enzyme NMT (myristoyl-CoA:protein N-myristoyltransferase) has been characterized in a range of species from Saccharomyces cerevisiae to Homo sapiens. NMT is essential for viability in a number of human pathogens, including the fungi Candida albicans and Cryptococcus neoformans, and the parasitic protozoa Leishmania major and Trypanosoma brucei. We have purified the Leishmania and T. brucei NMTs as active recombinant proteins and carried out kinetic analyses with their essential fatty acid donor, myristoyl-CoA and specific peptide substrates. A number of inhibitory compounds that target NMT in fungal species have been tested against the parasite enzymes in vitro and against live parasites in vivo. Two of these compounds inhibit TbNMT with IC50 values of <1 μM and are also active against mammalian parasite stages, with ED50 (the effective dose that allows 50% cell growth) values of 16–66 μM and low toxicity to murine macrophages. These results suggest that targeting NMT could be a valid approach for the development of chemotherapeutic agents against infectious diseases including African sleeping sickness and Nagana.

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Matovu, Enock, Thomas Seebeck, John C. K. Enyaru, and Ronald Kaminsky. "Drug resistance in Trypanosoma brucei spp., the causative agents of sleeping sickness in man and nagana in cattle." Microbes and Infection 3, no. 9 (2001): 763–70. http://dx.doi.org/10.1016/s1286-4579(01)01432-0.

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17

Lillico, Simon, Mark C. Field, Pat Blundell, Graham H. Coombs, and Jeremy C. Mottram. "Essential Roles for GPI-anchored Proteins in African Trypanosomes Revealed Using Mutants Deficient in GPI8." Molecular Biology of the Cell 14, no. 3 (2003): 1182–94. http://dx.doi.org/10.1091/mbc.e02-03-0167.

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The survival of Trypanosoma brucei, the causative agent of Sleeping Sickness and Nagana, is facilitated by the expression of a dense surface coat of glycosylphosphatidylinositol (GPI)-anchored proteins in both its mammalian and tsetse fly hosts. We have characterized T. brucei GPI8, the gene encoding the catalytic subunit of the GPI:protein transamidase complex that adds preformed GPI anchors onto nascent polypeptides. Deletion ofGPI8 (to give Δgpi8) resulted in the absence of GPI-anchored proteins from the cell surface of procyclic form trypanosomes and accumulation of a pool of non–protein-linked GPI molecules, some of which are surface located. Procyclic Δgpi8, while viable in culture, were unable to establish infections in the tsetse midgut, confirming that GPI-anchored proteins are essential for insect-parasite interactions. Applying specific inducible GPI8 RNAi with bloodstream form parasites resulted in accumulation of unanchored variant surface glycoprotein and cell death with a defined multinuclear, multikinetoplast, and multiflagellar phenotype indicative of a block in cytokinesis. These data show that GPI-anchored proteins are essential for the viability of bloodstream form trypanosomes even in the absence of immune challenge and imply that GPI8 is important for proper cell cycle progression.

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Chamond, Nathalie, Alain Cosson, Marie Christine Blom-Potar, et al. "Trypanosoma vivax Infections: Pushing Ahead with Mouse Models for the Study of Nagana. I. Parasitological, Hematological and Pathological Parameters." PLoS Neglected Tropical Diseases 4, no. 8 (2010): e792. http://dx.doi.org/10.1371/journal.pntd.0000792.

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19

Echodu, Richard, Mark Sistrom, Rosemary Bateta, et al. "Genetic Diversity and Population Structure of Trypanosoma brucei in Uganda: Implications for the Epidemiology of Sleeping Sickness and Nagana." PLOS Neglected Tropical Diseases 9, no. 2 (2015): e0003353. http://dx.doi.org/10.1371/journal.pntd.0003353.

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20

CAPEWELL, PAUL, ANNELI COOPER, CAROLINE CLUCAS, WILLIAM WEIR, and ANNETTE MACLEOD. "A co-evolutionary arms race: trypanosomes shaping the human genome, humans shaping the trypanosome genome." Parasitology 142, S1 (2014): S108—S119. http://dx.doi.org/10.1017/s0031182014000602.

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SUMMARYTrypanosoma brucei is the causative agent of African sleeping sickness in humans and one of several pathogens that cause the related veterinary disease Nagana. A complex co-evolution has occurred between these parasites and primates that led to the emergence of trypanosome-specific defences and counter-measures. The first line of defence in humans and several other catarrhine primates is the trypanolytic protein apolipoprotein-L1 (APOL1) found within two serum protein complexes, trypanosome lytic factor 1 and 2 (TLF-1 and TLF-2). Two sub-species of T. brucei have evolved specific mechanisms to overcome this innate resistance, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. In T. b. rhodesiense, the presence of the serum resistance associated (SRA) gene, a truncated variable surface glycoprotein (VSG), is sufficient to confer resistance to lysis. The resistance mechanism of T. b. gambiense is more complex, involving multiple components: reduction in binding affinity of a receptor for TLF, increased cysteine protease activity and the presence of the truncated VSG, T. b. gambiense-specific glycoprotein (TgsGP). In a striking example of co-evolution, evidence is emerging that primates are responding to challenge by T. b. gambiense and T. b. rhodesiense, with several populations of humans and primates displaying resistance to infection by these two sub-species.

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Mulenga, Gloria M., Lars Henning, Kalinga Chilongo, Chrisborn Mubamba, Boniface Namangala, and Bruce Gummow. "Insights into the Control and Management of Human and Bovine African Trypanosomiasis in Zambia between 2009 and 2019—A Review." Tropical Medicine and Infectious Disease 5, no. 3 (2020): 115. http://dx.doi.org/10.3390/tropicalmed5030115.

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Tsetse transmitted trypanosomiasis is a fatal disease commonly known as Nagana in cattle and sleeping sickness in humans. The disease threatens food security and has severe economic impact in Africa including most parts of Zambia. The level of effectiveness of commonly used African trypanosomiasis control methods has been reported in several studies. However, there have been no review studies on African trypanosomiasis control and management conducted in the context of One Health. This paper therefore seeks to fill this knowledge gap. A review of studies that have been conducted on African trypanosomiasis in Zambia between 2009 and 2019, with a focus on the control and management of trypanosomiasis was conducted. A total of 2238 articles were screened, with application of the search engines PubMed, PubMed Central and One Search. Out of these articles, 18 matched the required criteria and constituted the basis for the paper. An in-depth analysis of the 18 articles was conducted to identify knowledge gaps and evidence for best practices. Findings from this review provide stakeholders and health workers with a basis for prioritisation of African trypanosomiasis as an important neglected disease in Zambia and for formulation of One Health strategies for better control and/or management of the disease.

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CLAES, F., E. C. AGBO, M. RADWANSKA, et al. "How does Trypanosoma equiperdum fit into the Trypanozoon group? A cluster analysis by RAPD and Multiplex-endonuclease genotyping approach." Parasitology 126, no. 5 (2003): 425–31. http://dx.doi.org/10.1017/s0031182003002968.

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The pathogenic trypanosomes Trypanosoma equiperdum, T. evansi as well as T. brucei are morphologically identical. In horses, these parasites are considered to cause respectively dourine, surra and nagana. Previous molecular attempts to differentiate these species were not successful for T. evansi and T. equiperdum; only T. b. brucei could be differentiated to a certain extent. In this study we analysed 10 T. equiperdum, 8 T. evansi and 4 T. b. brucei using Random Amplified Polymorphic DNA (RAPD) and multiplex-endonuclease fingerprinting, a modified AFLP technique. The results obtained confirm the homogeneity of the T. evansi group tested. The T. b. brucei clustered out in a heterogenous group. For T. equiperdum the situation is more complex: 8 out of 10 T. equiperdum clustered together with the T. evansi group, while 2 T. equiperdum strains were more related to T. b. brucei. Hence, 2 hypotheses can be formulated: (1) only 2 T. equiperdum strains are genuine T. equiperdum causing dourine; all other T. equiperdum strains actually are T. evansi causing surra or (2) T. equiperdum does not exist at all. In that case, the different clinical outcome of horse infections with T. evansi or T. b. brucei is primarily related to the host immune response.

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Giordani, Federica, Daniel Paape, Isabel M. Vincent, et al. "Veterinary trypanocidal benzoxaboroles are peptidase-activated prodrugs." PLOS Pathogens 16, no. 11 (2020): e1008932. http://dx.doi.org/10.1371/journal.ppat.1008932.

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Livestock diseases caused by Trypanosoma congolense, T. vivax and T. brucei, collectively known as nagana, are responsible for billions of dollars in lost food production annually. There is an urgent need for novel therapeutics. Encouragingly, promising antitrypanosomal benzoxaboroles are under veterinary development. Here, we show that the most efficacious subclass of these compounds are prodrugs activated by trypanosome serine carboxypeptidases (CBPs). Drug-resistance to a development candidate, AN11736, emerged readily in T. brucei, due to partial deletion within the locus containing three tandem copies of the CBP genes. T. congolense parasites, which possess a larger array of related CBPs, also developed resistance to AN11736 through deletion within the locus. A genome-scale screen in T. brucei confirmed CBP loss-of-function as the primary mechanism of resistance and CRISPR-Cas9 editing proved that partial deletion within the locus was sufficient to confer resistance. CBP re-expression in either T. brucei or T. congolense AN11736-resistant lines restored drug-susceptibility. CBPs act by cleaving the benzoxaborole AN11736 to a carboxylic acid derivative, revealing a prodrug activation mechanism. Loss of CBP activity results in massive reduction in net uptake of AN11736, indicating that entry is facilitated by the concentration gradient created by prodrug metabolism.

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McGettrick, Anne F., Sarah E. Corcoran, Paul J. G. Barry та ін. "Trypanosoma bruceimetabolite indolepyruvate decreases HIF-1α and glycolysis in macrophages as a mechanism of innate immune evasion". Proceedings of the National Academy of Sciences 113, № 48 (2016): E7778—E7787. http://dx.doi.org/10.1073/pnas.1608221113.

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The parasiteTrypanasoma bruceicauses African trypanosomiasis, known as sleeping sickness in humans and nagana in domestic animals. These diseases are a major burden in the 36 sub-Saharan African countries where the tsetse fly vector is endemic. Untreated trypanosomiasis is fatal and the current treatments are stage-dependent and can be problematic during the meningoencephalitic stage, where no new therapies have been developed in recent years and the current drugs have a low therapeutic index. There is a need for more effective treatments and a better understanding of how these parasites evade the host immune response will help in this regard. The bloodstream form ofT. bruceiexcretes significant amounts of aromatic ketoacids, including indolepyruvate, a transamination product of tryptophan. This study demonstrates that this process is essential in bloodstream forms, is mediated by a specialized isoform of cytoplasmic aminotransferase and, importantly, reveals an immunomodulatory role for indolepyruvate. Indolepyruvate prevents the LPS-induced glycolytic shift in macrophages. This effect is the result of an increase in the hydroxylation and degradation of the transcription factor hypoxia-inducible factor-1α (HIF-1α). The reduction in HIF-1α levels by indolepyruvate, following LPS or trypanosome activation, results in a decrease in production of the proinflammatory cytokine IL-1β. These data demonstrate an important role for indolepyruvate in immune evasion byT. brucei.

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van Hellemond, J. J., F. R. Opperdoes, and A. G. M. Tielens. "The extraordinary mitochondrion and unusual citric acid cycle in Trypanosoma brucei." Biochemical Society Transactions 33, no. 5 (2005): 967–71. http://dx.doi.org/10.1042/bst0330967.

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African trypanosomes are parasitic protozoa that cause sleeping sickness and nagana. Trypanosomes are not only of scientific interest because of their clinical importance, but also because these protozoa contain several very unusual biological features, such as their specially adapted mitochondrion and the compartmentalization of glycolytic enzymes in glycosomes. The energy metabolism of Trypanosoma brucei differs significantly from that of their hosts and changes drastically during the life cycle. Despite the presence of all citric acid cycle enzymes in procyclic insect-stage T. brucei, citric acid cycle activity is not used for energy generation. Recent investigations on the influence of substrate availability on the type of energy metabolism showed that absence of glycolytic substrates did not induce a shift from a fermentative metabolism to complete oxidation of substrates. Apparently, insect-stage T. brucei use parts of the citric acid cycle for other purposes than for complete degradation of mitochondrial substrates. Parts of the cycle are suggested to be used for (i) transport of acetyl-CoA units from the mitochondrion to the cytosol for the biosynthesis of fatty acids, (ii) degradation of proline and glutamate to succinate, (iii) generation of malate, which can then be used for gluconeogenesis. Therefore the citric acid cycle in trypanosomes does not function as a cycle.

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Namangala, Boniface, Chihiro Sugimoto та Noboru Inoue. "Effects of Exogenous Transforming Growth Factor β on Trypanosoma congolense Infection in Mice". Infection and Immunity 75, № 4 (2007): 1878–85. http://dx.doi.org/10.1128/iai.01452-06.

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ABSTRACT The socioeconomic implications of trypanosomosis in sub-Saharan Africa and the limitations of its current control regimes have stimulated research into alternative control methods. Considering the pro- and anti-inflammatory properties of transforming growth factor β1 (TGF-β1) and its potential to enhance immunity against protozoan parasites, we examined the effects of intraperitoneally delivered TGF-β1 in C57BL/6 mice infected with Trypanosoma congolense, the hemoprotozoan parasite causing nagana in cattle. A triple dose of 10 ng TGF-β1 significantly reduced the first parasitemic peak and delayed mortality of infected mice. Furthermore, exogenous TGF-β1 significantly decreased the development of trypanosome-induced anemia and splenomegaly. The apparent TGF-β1-induced antitrypanosome protection, occurring mainly during the early stage of infection, correlated with an enhanced parasite antigen-specific Th1 cell response characterized by a skewed type I cytokine response and a concomitant stronger antitrypanosome immunoglobulin G2a antibody response. Infected TGF-β1-pretreated mice exhibited a significant reduction in the trypanosome-induced hyperexpansion of B cells. Furthermore, evidence is provided herein that exogenous TGF-β1 activates macrophages that may contribute to parasite control. Collectively, these data indicate that exogenous TGF-β1 is immunostimulative, inducing partial protection against T. congolense infection, possibly through mechanisms involving innate immune responses.

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Hoppenheit, Antje, Stephan Steuber, Burkhard Bauer, et al. "Host preference of tsetse: an important tool to appraise the Nagana risk of cattle in the cotton zone of Mali." Wiener klinische Wochenschrift 122, S3 (2010): 81–86. http://dx.doi.org/10.1007/s00508-010-1443-9.

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Mosimann, Marc, Shinobu Goshima, Tanja Wenzler, Alexandra Lüscher, Nobuyuki Uozumi, and Pascal Mäser. "A Trk/HKT-Type K+ Transporter from Trypanosoma brucei." Eukaryotic Cell 9, no. 4 (2010): 539–46. http://dx.doi.org/10.1128/ec.00314-09.

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ABSTRACT The molecular mechanisms of K+ homeostasis are only poorly understood for protozoan parasites. Trypanosoma brucei subsp. parasites, the causative agents of human sleeping sickness and nagana, are strictly extracellular and need to actively concentrate K+ from their hosts’ body fluids. The T. brucei genome contains two putative K+ channel genes, yet the trypanosomes are insensitive to K+ antagonists and K+ channel-blocking agents, and they do not spontaneously depolarize in response to high extracellular K+ concentrations. However, the trypanosomes are extremely sensitive to K+ ionophores such as valinomycin. Surprisingly, T. brucei possesses a member of the Trk/HKT superfamily of monovalent cation permeases which so far had only been known from bacteria, archaea, fungi, and plants. The protein was named TbHKT1 and functions as a Na+-independent K+ transporter when expressed in Escherichia coli, Saccharomyces cerevisiae, or Xenopus laevis oocytes. In trypanosomes, TbHKT1 is expressed in both the mammalian bloodstream stage and the Tsetse fly midgut stage; however, RNA interference (RNAi)-mediated silencing of TbHKT1 expression did not produce a growth phenotype in either stage. The presence of HKT genes in trypanosomatids adds a further piece to the enigmatic phylogeny of the Trk/HKT superfamily of K+ transporters. Parsimonial analysis suggests that the transporters were present in the first eukaryotes but subsequently lost in several of the major eukaryotic lineages, in at least four independent events.

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Alam, Uzma, Chaz Hyseni, Rebecca E. Symula, et al. "Implications of Microfauna-Host Interactions for Trypanosome Transmission Dynamics in Glossina fuscipes fuscipes in Uganda." Applied and Environmental Microbiology 78, no. 13 (2012): 4627–37. http://dx.doi.org/10.1128/aem.00806-12.

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ABSTRACTTsetse flies (Diptera: Glossinidae) are vectors for African trypanosomes (Euglenozoa: kinetoplastida), protozoan parasites that cause African trypanosomiasis in humans (HAT) and nagana in livestock. In addition to trypanosomes, two symbiotic bacteria (Wigglesworthia glossinidiaandSodalis glossinidius) and two parasitic microbes,Wolbachiaand a salivary gland hypertrophy virus (SGHV), have been described in tsetse. Here we determined the prevalence of and coinfection dynamics betweenWolbachia, trypanosomes, and SGHV inGlossina fuscipes fuscipesin Uganda over a large geographical scale spanning the range of host genetic and spatial diversity. Using a multivariate analysis approach, we uncovered complex coinfection dynamics between the pathogens and statistically significant associations between host genetic groups and pathogen prevalence. It is important to note that these coinfection dynamics and associations with the host were not apparent by univariate analysis. These associations between host genotype and pathogen are particularly evident forWolbachiaand SGHV where host groups are inversely correlated forWolbachiaand SGHV prevalence. On the other hand, trypanosome infection prevalence is more complex and covaries with the presence of the other two pathogens, highlighting the importance of examining multiple pathogens simultaneously before making generalizations about infection and spatial patterns. It is imperative to note that these novel findings would have been missed if we had employed the standard univariate analysis used in previous studies. Our results are discussed in the context of disease epidemiology and vector control.

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Brown, K. "From Ubombo to Mkhuzi: Disease, Colonial Science, and the Control of Nagana (Livestock Trypanosomosis) in Zululand, South Africa, c. 1894-1953." Journal of the History of Medicine and Allied Sciences 63, no. 3 (2008): 285–322. http://dx.doi.org/10.1093/jhmas/jrn003.

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Krstin, Sonja, Herbenya Silva Peixoto, and Michael Wink. "Combinations of Alkaloids Affecting Different Molecular Targets with the Saponin Digitonin Can Synergistically Enhance Trypanocidal Activity against Trypanosoma brucei brucei." Antimicrobial Agents and Chemotherapy 59, no. 11 (2015): 7011–17. http://dx.doi.org/10.1128/aac.01315-15.

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ABSTRACTThe flagellateTrypanosoma bruceicauses sleeping sickness in humans and nagana in animals. Only a few drugs are registered to treat trypanosomiasis, but those drugs show severe side effects. Also, because some pathogen strains have become resistant, new strategies are urgently needed to combat this parasitic disease. An underexplored possibility is the application of combinations of several trypanocidal agents, which may potentiate their trypanocidal activity in a synergistic fashion. In this study, the potential synergism of mutual combinations of bioactive alkaloids and alkaloids with a membrane-active steroidal saponin, digitonin, was explored with regard to their effect onT. b. brucei. Alkaloids were selected that affect different molecular targets: berberine and chelerythrine (intercalation of DNA), piperine (induction of apoptosis), vinblastine (inhibition of microtubule assembly), emetine (intercalation of DNA, inhibition of protein biosynthesis), homoharringtonine (inhibition of protein biosynthesis), and digitonin (membrane permeabilization and uptake facilitation of polar compounds). Most combinations resulted in an enhanced trypanocidal effect. The addition of digitonin significantly stimulated the activity of almost all alkaloids against trypanosomes. The strongest effect was measured in a combination of digitonin with vinblastine. The highest dose reduction indexes (DRI) were measured in the two-drug combination of digitonin or piperine with vinblastine, where the dose of vinblastine could be reduced 9.07-fold or 7.05-fold, respectively. The synergistic effects of mutual combinations of alkaloids and of alkaloids with digitonin present a new avenue to treat trypanosomiasis but one which needs to be corroborated in future animal experiments.

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Oli, Monika W., Laura F. Cotlin, April M. Shiflett, and Stephen L. Hajduk. "Serum Resistance-Associated Protein Blocks Lysosomal Targeting of Trypanosome Lytic Factor in Trypanosoma brucei." Eukaryotic Cell 5, no. 1 (2006): 132–39. http://dx.doi.org/10.1128/ec.5.1.132-139.2006.

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ABSTRACT Trypanosoma brucei brucei is the causative agent of nagana in cattle and can infect a wide range of mammals but is unable to infect humans because it is susceptible to the innate cytotoxic activity of normal human serum. A minor subfraction of human high-density lipoprotein (HDL) containing apolipoprotein A-I (apoA-I), apolipoprotein L-I (apoL-I), and haptoglobin-related protein (Hpr) provides this innate protection against T. b. brucei infection. This HDL subfraction, called trypanosome lytic factor (TLF), kills T. b. brucei following receptor binding, endocytosis, and lysosomal localization. Trypanosoma brucei rhodesiense, which is morphologically and physiologically indistinguishable from T. b. brucei, is resistant to TLF-mediated killing and causes human African sleeping sickness. Human infectivity by T. b. rhodesiense correlates with the evolution of a resistance-associated protein (SRA) that is able to ablate TLF killing. To examine the mechanism of TLF resistance, we transfected T. b. brucei with an epitope-tagged SRA gene. Transfected T. b. brucei expressed SRA mRNA at levels comparable to those in T. b. rhodesiense and was highly resistant to TLF. In the SRA-transfected cells, intracellular trafficking of TLF was altered, with TLF being mainly localized to a subset of SRA-containing cytoplasmic vesicles but not to the lysosome. These results indicate that the cellular distribution of TLF is influenced by SRA expression and may directly determine the organism's susceptibility to TLF.

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Chang, Tunhan, Kenneth G. Milne, Maria Lucia Sampaio Güther, Terry K. Smith, and Michael A. J. Ferguson. "Cloning ofTrypanosoma bruceiandLeishmania majorGenes Encoding the GlcNAc-Phosphatidylinositol De-N-acetylase of Glycosylphosphatidylinositol Biosynthesis That Is Essential to the African Sleeping Sickness Parasite." Journal of Biological Chemistry 277, no. 51 (2002): 50176–82. http://dx.doi.org/10.1074/jbc.m208374200.

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The second step of glycosylphosphatidylinositol anchor biosynthesis in all eukaryotes is the conversion of D-GlcNAcα1–6-d-myo-inositol-1-HPO4-sn-1,2-diacylglycerol (GlcNAc-PI) tod-GlcNα1–6-d-myo-inositol-1-HPO4-sn-1,2-diacylglycerol by GlcNAc-PI de-N-acetylase. The genes encoding this activity arePIG-LandGPI12in mammals and yeast, respectively. Fragments of putative GlcNAc-PI de-N-acetylase genes fromTrypanosoma bruceiandLeishmania majorwere identified in the respective genome project data bases. The full-length genesTbGPI12andLmGPI12were subsequently cloned, sequenced, and shown to complement aPIG-L-deficient Chinese hamster ovary cell line and restore surface expression of GPI-anchored proteins. A tetracycline-inducible bloodstream formT. brucei TbGPI12conditional null mutant cell line was created and analyzed under nonpermissive conditions.TbGPI12mRNA levels were reduced to undetectable levels within 8 h of tetracycline removal, and the cells died after 3–4 days. This demonstrates thatTbGPI12is an essential gene for the tsetse-transmitted parasite that causes Nagana in cattle and African sleeping sickness in humans. It also validates GlcNAc-PI de-N-acetylase as a potential drug target against these diseases. Washed parasite membranes were prepared from the conditional null mutant parasites after 48 h without tetracycline. These membranes were shown to be greatly reduced in GlcNAc-PI de-N-acetylase activity, but they retained their ability to make GlcNAc-PI and to processd-GlcNα1–6-d-myo-inositol-1-HPO4-sn-1,2-diacylglycerol to later glycosylphosphatidylinositol intermediates. These results suggest that the stabilities of other glycosylphosphatidylinositol pathway enzymes are not dependent on GlcNAc-PI de-N-acetylase levels.

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Yang, Xiao, Xuelei Wu, Jiahai Zhang, et al. "Recognition of hyperacetylated N-terminus of H2AZ by TbBDF2 from Trypanosoma brucei." Biochemical Journal 474, no. 22 (2017): 3817–30. http://dx.doi.org/10.1042/bcj20170619.

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Histone modification plays an important role in various biological processes, including gene expression regulation. Bromodomain, as one of histone readers, recognizes specifically the ε-N-lysine acetylation (KAc) of histone. Although the bromodomains and histone acetylation sites of Trypanosoma brucei (T. brucei), a lethal parasite responsible for sleeping sickness in human and nagana in cattle, have been identified, how acetylated histones are recognized by bromodomains is still unknown. Here, the bromodomain factor 2 (TbBDF2) from T. brucei was identified to be located in the nucleolus and bind to the hyperacetylated N-terminus of H2AZ which dimerizes with H2BV. The bromodomain of TbBDF2 (TbBDF2-BD) displays a conserved fold that comprises a left-handed bundle of four α-helices (αZ, αA, αB, αC), linked by loop regions of variable length (ZA and BC loops), which form the KAc-binding pocket. NMR chemical shift perturbation further revealed that TbBDF2-BD binds to the hyperacetylated N-terminus of H2AZ through its KAc-binding pocket. By structure-based virtual screening combining with the ITC experiment, a small molecule compound, GSK2801, was shown to have high affinity to TbBDF2-BD. GSK2801 and the hyperacetylated N-terminus of H2AZ have similar binding sites on TbBDF2-BD. In addition, GSK2801 competitively inhibits the hyperacetylated N-terminus of H2AZ binding to TbBDF2-BD. After treatment of GSK2801, cell growth was inhibited and localization of TbBDF2 was disrupted. Our results report a novel bromodomain-histone recognition by TbBDF2-BD and imply that TbBDF2 may serve as a potential chemotherapeutic target for the treatment of trypanosomiasis.

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Wall, Richard J., Eva Rico, Iva Lukac, et al. "Clinical and veterinary trypanocidal benzoxaboroles target CPSF3." Proceedings of the National Academy of Sciences 115, no. 38 (2018): 9616–21. http://dx.doi.org/10.1073/pnas.1807915115.

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African trypanosomes cause lethal and neglected tropical diseases, known as sleeping sickness in humans and nagana in animals. Current therapies are limited, but fortunately, promising therapies are in advanced clinical and veterinary development, including acoziborole (AN5568 or SCYX-7158) and AN11736, respectively. These benzoxaboroles will likely be key to the World Health Organization’s target of disease control by 2030. Their mode of action was previously unknown. We have developed a high-coverage overexpression library and use it here to explore drug mode of action in Trypanosoma brucei. Initially, an inhibitor with a known target was used to select for drug resistance and to test massive parallel library screening and genome-wide mapping; this effectively identified the known target and validated the approach. Subsequently, the overexpression screening approach was used to identify the target of the benzoxaboroles, Cleavage and Polyadenylation Specificity Factor 3 (CPSF3, Tb927.4.1340). We validated the CPSF3 endonuclease as the target, using independent overexpression strains. Knockdown provided genetic validation of CPSF3 as essential, and GFP tagging confirmed the expected nuclear localization. Molecular docking and CRISPR-Cas9-based editing demonstrated how acoziborole can specifically block the active site and mRNA processing by parasite, but not host CPSF3. Thus, our findings provide both genetic and chemical validation for CPSF3 as an important drug target in trypanosomes and reveal inhibition of mRNA maturation as the mode of action of the trypanocidal benzoxaboroles. Understanding the mechanism of action of benzoxaborole-based therapies can assist development of improved therapies, as well as the prediction and monitoring of resistance, if or when it arises.

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McConville, Malcolm J., Kylie A. Mullin, Steven C. Ilgoutz, and Rohan D. Teasdale. "Secretory Pathway of Trypanosomatid Parasites." Microbiology and Molecular Biology Reviews 66, no. 1 (2002): 122–54. http://dx.doi.org/10.1128/mmbr.66.1.122-154.2002.

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SUMMARY The Trypanosomatidae comprise a large group of parasitic protozoa, some of which cause important diseases in humans. These include Trypanosoma brucei (the causative agent of African sleeping sickness and nagana in cattle), Trypanosoma cruzi (the causative agent of Chagas' disease in Central and South America), and Leishmania spp. (the causative agent of visceral and [muco]cutaneous leishmaniasis throughout the tropics and subtropics). The cell surfaces of these parasites are covered in complex protein- or carbohydrate-rich coats that are required for parasite survival and infectivity in their respective insect vectors and mammalian hosts. These molecules are assembled in the secretory pathway. Recent advances in the genetic manipulation of these parasites as well as progress with the parasite genome projects has greatly advanced our understanding of processes that underlie secretory transport in trypanosomatids. This article provides an overview of the organization of the trypanosomatid secretory pathway and connections that exist with endocytic organelles and multiple lytic and storage vacuoles. A number of the molecular components that are required for vesicular transport have been identified, as have some of the sorting signals that direct proteins to the cell surface or organelles in the endosome-vacuole system. Finally, the subcellular organization of the major glycosylation pathways in these parasites is reviewed. Studies on these highly divergent eukaryotes provide important insights into the molecular processes underlying secretory transport that arose very early in eukaryotic evolution. They also reveal unusual or novel aspects of secretory transport and protein glycosylation that may be exploited in developing new antiparasite drugs.

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Pagabeleguem, Soumaïla, Ange Irénée Toé, Sié Hermann Pooda, et al. "Optimizing the feeding frequency to maximize the production of sterile males in tsetse mass-rearing colonies." PLOS ONE 16, no. 1 (2021): e0245503. http://dx.doi.org/10.1371/journal.pone.0245503.

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Tsetse flies are cyclical vectors of trypanosomes, the causative agents of sleeping sickness or Human African Trypanosomosis and nagana or African Animal Trypanosomosis in Sub-Saharan Africa. The Insectarium de Bobo-Dioulasso (IBD) was created and equipped in the frame of Pan African Tsetse and Trypanosomosis Eradication Campaign (PATTEC) with the main goal to provide sterile males for the different eradication programs in West Africa which is already the case with the ongoing eradication program in Senegal. The aim of this study was to identify the best feeding regime in mass-rearing colonies of Glossina palpalis gambiensis to optimize the yield of sterile males. We investigated the mortality and fecundity for various feeding regimes and day alternation (3×: Monday-Wednesday-Friday, 4×: Monday-Wednesday-Friday-Saturday, 4×: Monday-Wednesday-Thursday-Friday and 6×: all days except Sunday) on adult tsetse flies in routine rearing over 60 days after emergence. The day alternation in the 4 blood meals per week (feeding regimes 2 and 3) had no effect on tsetse fly mortality and fecundity. The best feeding regime was the regime of 4 blood meals per week which resulted in higher significant fecundity (PPIF = 2.5; P = 0.003) combined with lower mortality of females (P = 0.0003) than the 3 blood meals per week (PPIF = 2.0) and in similar fecundity (PPIF = 2.6; P = 0.70) and mortality (P = 0.51) than the 6 blood meals per week. This feeding regime was extended to the whole colonies, resulting in an improved yield of sterile males for the ongoing eradication program in Senegal and would be more cost-effective for the implementation of the next-coming sterile insect technique (SIT) programs in West Africa.

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Hustiany, Rini, Emy Rahmawati, and Alia Rahmi. "DEVELOPMENT POTENTIAL OF NAGARA BEAN (Vigna unguiculata ssp. Cylindrica) CULTIVATED IN FRESHWATER SWAMPLANDS FOR PROCESSED FOOD." TROPICAL WETLAND JOURNAL 2, no. 3 (2016): 30–36. http://dx.doi.org/10.20527/twj.v2i3.37.

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Nagara bean/ catjang (Vigna unguiculata spp. Cylindrica) is a subspecies of cowpea which is widely cultivated in freshwater swamplands of Daha Utara and Daha Selatan sub-districts, Hulu Sungai Selatan Regency. Nagara bean is a plant native to South Kalimantan, but its utilization is still very low compared to other cowpeas. The aims of this study were to analyze the chemical and physical characteristics of Nagara bean in processed food compared to those of soybeans; and to analyze the development potential of Nagara bean in processed food. The methods were the production of catjang flour from skinless Nagara beans; the production of catjang flour by roasting Nagara beans; the substitution of Nagara beans with coagulated and fermented soybeans. The results showed that the flour from skinless Nagara beans contained protein (24.16%) and carbohydrate (61.62%), while the flour from roasted Nagara beans contained protein (18.42%) and carbohydrate (69.33%). When compared to soybeans, papan and arabian beans, the two types of Nagara bean, could be coagulated with a higher water content and lower protein content. When Nagara beans were fermented, the water and protein contents of fermented beans were higher than those of soybeans. It can be concluded that Nagara beans could be used in processed foods chemically. Nagara beans however absorbed water easily, so they smelled sour and unpleasant and the texture became soft.

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Zhou, Ning-Yi, Jumáa Al-Dulayymi, Mark S. Baird, and Peter A. Williams. "Salicylate 5-Hydroxylase from Ralstonia sp. Strain U2: a Monooxygenase with Close Relationships to and Shared Electron Transport Proteins with Naphthalene Dioxygenase." Journal of Bacteriology 184, no. 6 (2002): 1547–55. http://dx.doi.org/10.1128/jb.184.6.1547-1555.2002.

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ABSTRACT The genes from the oxygenase cluster nagAaGHAbAcAd of naphthalene-degrading Ralstonia sp. strain U2 were cloned and overexpressed. Salicylate 5-hydroxylase (S5H) activity, converting salicylate to gentisate, was present in vitro only in the single extract of cells with overexpressed nagAaGHAb or in a mixture of three cell extracts containing, respectively, NagGH (the oxygenase components), NagAa (ferredoxin reductase), and NagAb (ferredoxin). Each of the three extracts required for S5H activity was rate limiting in the presence of excess of the others but, when in excess, did not affect the rate of catalysis. S5H catalyzed the 5-hydroxylation of the aromatic rings of 3- and 4-substituted salicylates. However, the methyl group of 5-methylsalicylate was hydroxylated to produce the 5-hydroxymethyl derivative and the 6-position on the ring of 5-chlorosalicylate was hydroxylated, producing 5-chloro-2,6-dihydroxybenzoate. In an assay for the nag naphthalene dioxygenase (NDO) based on the indole-linked oxidation of NADH, three extracts were essential for activity (NagAcAd, NagAa, and NagAb). NDO and S5H were assayed in the presence of all possible combinations of the nag proteins and the corresponding nah NDO proteins from the “classical” naphthalene degrader P. putida NCIMB9816. All three oxygenase components functioned with mixed combinations of the electron transport proteins from either strain. The S5H from strain U2 is a unique monooxygenase which shares sequence similarity with dioxygenases such as NDO but is also sufficiently similar in structure to interact with the same electron transport chain and probably does so in vivo during naphthalene catabolism in strain U2.

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Hakuta, Keisuke, and Tsuyoshi Takagi. "Sign of Permutation Induced by Nagata Automorphism over Finite Fields." Journal of Mathematics Research 9, no. 5 (2017): 54. http://dx.doi.org/10.5539/jmr.v9n5p54.

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This paper proves that the Nagata automorphism over a finite field can be mimicked by a tame automorphism which is a composition of four elementary automorphisms. By investigating the sign of the permutations induced by the above elementary automorphisms, one can see that if the Nagata automorphism is defined over a prime field of characteristic two, the Nagata automorphism induces an odd permutation, and otherwise, the Nagata automorphism induces an even permutation.

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Chatterjee, Prerana. "Managing Urban Transformations of Refugee Settlements in West Delhi from Camps to Nagars: The Story of Moti Nagar and Kirti Nagar." CREATIVE SPACE 2, no. 2 (2015): 189–216. http://dx.doi.org/10.15415/cs.2015.22011.

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Chechet, G. D., J. Yahaya, and A. J. Nok. "In vitro and in vivo anti-trypanosomal potentials of Afrormosia laxiflora and Khaya senegalensis against Trypanosoma brucei brucei." Nigerian Veterinary Journal 39, no. 3 (2018): 269–84. http://dx.doi.org/10.4314/nvj.v39i3.10.

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Animal African trypanosomiasis (AAT) also known as Nagana is a resurgent disease in Africa. Medicinal plants are being used in less developed countries for the treatment of various diseases including trypanosomiasis, due to the high cost of currently available drugs. Most of these plants have been useful sources of treatment of various diseases based on information obtained from folk medicine but have not been scientifically certified. Here, we investigated the in vitro and in vivo anti-trypanosomal potentials of the methanol extract of Aformorsia laxiflora and Khaya senegalensis against T. b. brucei. Phytochemical screening as well as LD50 of the plant extracts was carried out following standard procedures. Parasitemia was monitored daily while Packed Cell Volume was determined at three time points (days 1, 4 and 7) during the course of the infection. The phytochemical analysis showed the presence of saponins, alkaloids, flavonoids, antraquinones, resins and tanins. However, steriods/terpenoids were absent in K. senegalensis but present in A. laxiflora. The toxicity of methanol extract of both A. laxiflora and K. senegalensis was above 5000mg/kg body weight. Methanol extracts of A. laxiflora (leaves) and K. senegalensis (stem bark) showed promising trypanocidal potential in vitro against T. b. brucei at concentrations of 10, 15, 25mg/ml and 40 and 20mg/ml respectively. At these concentrations, both extracts immobilized the parasites within 55mins post-incubation. In general, A. laxiflora leaf extract demonstrated prophylactic activity against T. b. brucei in vivo at a dose of 500mg/Kg body weight particularly in group C animals where a delayed pre-patent period (6 days post-infection), extended survival (14 days post-infection) and significant (P<0.05) reduction in the parasite burden confirmed by an absence of anemia (PCV 47.00±0.8 %) was observed when compared to the infected untreated control group. K. senegalensis extract on the other hand did not show anti-trypanosomal activity in the treated groups (1, 2, and 3). Based on these observations, it was therefore deduced that the methanol extract of leaves of A. laxiflora possessed the ability to ameliorate the burden of the disease and could be a plausible candidate for drug development against the disease.Keywords: Trypanosoma brucei brucei, Afromosia laxiflora, Khaya senegalensis, anti-trypanosomal, in vitro, in vivo

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Zulkarnein, Satria, Yusrizal Yusrizal, and Niswanto Niswanto. "KONTRIBUSI MAJELIS PENDIDIKAN DAERAH KABUPATEN NAGAN RAYA DALAM PEMBANGUNAN PENDIDIKAN." Visipena 11, no. 2 (2020): 316–33. http://dx.doi.org/10.46244/visipena.v11i2.1214.

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Regional Education Council of Nagan Raya have a role as an independent community-based organization which give its contributions in giving solution or consideration to local government in deciding the education policies. The aims of this research were to find out the planning, the mechanism, the evaluation and the obstacles which faced by Regional Education Council of Nagan Raya in giving its educational contributions. This research was conducted by descriptive method through qualitative approach. The research showed that: (1) Regional Education Council of Nagan Raya has only implemented 7 programs in order to give its contributions to the local government in order develop education quality. (2) The mechanism of program implementation is implemented by a good management through focused on planning, organizing, actuating and controlling. (3) The evaluation which made in every program is implemented by a comprehensive evaluation which focused on every problem and gap which occurred. (4) The main obstacle which faced by Regional Education Council Nagan Raya in giving its educational contributions are about Regent’s political will and the deficit of district budget. Abstrak Majelis Pendidikan Nagan Raya memiliki peran sebagai lembaga independen yang berbasis masyarakat. Tujuan dari penelitian ini adalah untuk mengetahui: perencanaan program, mekanisme pelaksanaan program, evaluasi program dan hambatan-hambatan yang dihadapi Majelis Pendidikan Daerah Kabupaten Nagan Raya dalam memberikan kontribusi pembangunan pendidikan di Kabupaten Nagan Raya. Penelitian ini menggunakan metode deskriptif dengan pendekatan kualitatif. Hasil penelitian menunjukan bahwa: (1) Majelis Pendidikan Daerah Kabupaten Nagan Raya telah melaksanakan 7 program yang sesuai dengan tugas dan wewenang yang diamanahkan dalam qanun yang berlaku. (2) Mekanisme pelaksanaan program yang dilakukan Majelis Pendidikan Daerah Nagan Raya dijalankan dengan manajemen yang baik yaitu dengan melaksanakan planning, organizing, actuating dan controlling. (3) Evaluasi yang dilakukan Majelis Pendidikan Daerah Kabupaten Nagan Raya tidak dilaksanakan dengan menjalankan fungsi manajemen dengan baik, mealainkam hanya berfokus pada setiap masalah atau kesenjangan yang terjadi pada setiap program melalui observasi langsung. (4) Hambatan utama yang ditemukan Majelis Pendidikan Daerah Kabupaten Nagan Raya dalam memberikan kontribusinya pendidikannya adalah Political Will dari Bupati Nagan Raya serta defisitnya anggaran daerah.

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Fatimah, Siti. "Diversifikasi Dagangan Pedagang Nagara Di Pasar Margasari Kecamatan Candi Laras Kabupaten Tapin." PADARINGAN (Jurnal Pendidikan Sosiologi Antropologi) 3, no. 3 (2021): 437. http://dx.doi.org/10.20527/padaringan.v3i3.3970.

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Pasar merupakan tempat bertemu antara penjual dan pembeli. Berbagai aktivitas jual beli dilakukan di pasar bahakan pasar sendiri dibedakan menjadi dua yaitu ada pasar yang bersifat tradisional dan ada pasar yang bersifat modern. Komponen yang paling penting agar pasar tetap berjalan yaitu adanya pedagang dan pembeli, pedagang yang ada di Kalimantan Selatan sendiri ada yang masih bersifat tradisional dimana mereka dikenal sejak dulu sebagai pedagang yang biasa menjual barang dagangannya dengan menggunakan kapal. Masyarakat menyebutnya dengan sebutan pedagang Nagara karena mereka berasal dari Daerah Nagara. Ada beberapa hal yang dilakukan para pedagang Nagara tersebut agar tetap dapat bertahan serta bersaing dengan pedagang lainnya. Penelitian ini bertujuan untuk mendapatkan gambaran mengenai diversifikasi dagangan pedagang Nagara di Pasar Margasari Kecamatan Candi Laras Kabupaten Tapin.

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Cyranoski, David. "Shigekazu Nagata." Nature Medicine 7, no. 7 (2001): 759. http://dx.doi.org/10.1038/89860.

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Jara, Pascual. "Nagata rings." Frontiers of Mathematics in China 10, no. 1 (2014): 91–110. http://dx.doi.org/10.1007/s11464-014-0388-0.

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Setiawati, Evy. "PEMANFAATAN TEPUNG TERMODIFIKASI UMBI RAWA DAN TEPUNG REBUNG SEBAGAI COATING FLOUR PRODUK GORENGAN." Jurnal Riset Industri Hasil Hutan 7, no. 1 (2015): 9. http://dx.doi.org/10.24111/jrihh.v7i1.852.

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Tingkat penyerapan tepung terigu sebagai bahan penyalut terhadap minyak cukup tinggi. Penyerapan minyak goreng yang terlalu tinggi pada produk akan mempengaruhi tampilan dan rasa produk. Disamping itu, kandungan lemak akibat penyerapan minyak goreng yang tinggi dapat mengganggu kesehatan konsumen. Tepung umbi alabio dan umbi nagara dapat dijadikan alternatif coating flour karena termasuk jenis tepung berpati. Penelitian ini bertujuan menganalisa pengaruh tepung termodifikasi umbi alabio, umbi nagara dan rebung terhadap tingkat penyerapan minyak goreng. Penelitian dilakukan melalui beberapa tahap, pembuatan tepung termodifikasi berbahan baku umbi alabio, umbi nagara, dan rebung; formulasi tepung termodifikasi; pengujian tepung termodifikasi, pembuatan produk coating flour; dan pengujian produk gorengan. Semakin banyak tepung modifikasi umbi nagara yang ditambahkan maka minyak yang diserap pun semakin tinggi. Komposisi tepung modifikasi umbi alabio dan tepung rebung dengan komposisi 90:10 lebih dipilih sebagai coating flour karena mempunyai kandungan amilosa yang tinggi, viskositas puncak yang rendah. Karakter coating flour tersebut mampu menghasilkan aneka gorengan yang rendah lemak, tinggi karbohidrat, tinggi serat pangan, dan rendah tingkat penyerapan minyaknya.

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Kishimoto, Takashi. "A new proof of the non-tameness of the Nagata automorphism from the point of view of the Sarkisov program." Compositio Mathematica 144, no. 4 (2008): 963–77. http://dx.doi.org/10.1112/s0010437x07003399.

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AbstractThe Nagata automorphism is a kind of complicated automorphism on the affine 3-space ${\mathbb C}^3$. For a long time, it remained unknown whether or not the Nagata automorphism is tame until Shestakov and Umirbaev at last proved that it is not tame in 2004, by purely algebraic methods (e.g. Poisson algebra). In this paper, we consider a certain necessary condition for a given automorphism on ${\mathbb C}^3$ to be tame from the point of view of the Sarkisov program established by Corti. Furthermore, by using it, we shall give a new algebro-geometric proof of the non-tameness of the Nagata automorphism.

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Hakuta, Keisuke. "Sign of Permutations Induced by Anick and Nagata-Anick Automorphisms over Finite Fields." Journal of Mathematics Research 9, no. 4 (2017): 23. http://dx.doi.org/10.5539/jmr.v9n4p23.

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In this paper, we investigate the sign of permutations induced by the Anick automorphism and the Nagata-Anick automorphism over finite fields. We shall prove that if the Anick automorphism and the Nagata-Anick automorphism are defined over a prime field of characteristic two, they induce odd permutations, and otherwise, they induce even permutations.

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Irhas, Zulfikar. "Pencadangan dan Pelestarian Fungsi Ekosistem Gambut di Kabupaten Nagan Raya." Syiah Kuala Law Journal 1, no. 3 (2017): 119–31. http://dx.doi.org/10.24815/sklj.v1i3.9642.

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Nagan Raya salah satu Kabupaten yang ada di Provinsi Aceh yang mempunyai ekosistem gambut, dalam rangka pemeliharaan ekosistem gambut sebagaimana diatur di dalam Pasal 33 Peraturan Pemerintah Nomor 71 Tahun 2014 tentang Pengelolaan dan Perlindungan Ekosistem Gambut menyebutkan “pemeliharaan ekosistem gambut sebagaimana dimaksud dalam Pasal 17 ayat (1) huruf b dilakukan melalui upaya pencadangan ekosistem gambut dan pelestarian fungsi ekosistem gambut sebagai pengendali dampak perubahan iklim. Pemerintah Kabupaten Nagan Raya telah menetapkan ekosistem gambut dengan fungsi lindung dalam Pasal 27 ayat (2) Qanun Kabupaten Nagan Raya Nomor 11 Tahun 2015 tentang Rencana Tata Ruang dan Wilayah Kabupaten Nagan Raya kawasan lindung gambut sebagaimana dimaksud pada ayat (1) seluas 11.380,71 ha terletak di Kecamatan Darul Makmur, berada di Gampong Babah Lueng, Kuala Seumayam, Pulo Kruet, dan Sumber Bakti. Praktinya, ekosistem gambut tersebut telah dimanfaatkan sehingga fungsi dari kawasan tersebut telah beralih. Hasil penelitian ini menunjukkan bahwa upaya pencadangan dan pelestarian fungsi ekosistem gambut di Kabupaten Nagan Raya tidak dilakukan secara maksimal sehingga eksploitasi rawa gambut masih terus terjadi pada ekosistem gambut dengan fungsi lindung.Nagan Raya is one of regencies in Aceh Province that has peat ecosystem region, concerning the protection of peat ecosystem as regulated in Article 33 of the Government Regulation Number 71, 2014 regarding Ecosystem Management and Protection of peat states that an effort of taking care peat ecosystem as worded in Article 17 ( 1 ) point b is done through the reservation of peat ecosystem and conservation function as controller of climate change impact. The District Government of Nagan Raya has determined that the protection function of peat ecosystem and sustainability function into Article 27 ( 2 ) Nagan Raya District Local Law (Qanun) Number 11, 2015 regarding spatial planning and Nagan Raya District Area of peat ecosystem as meant by versus ( 1 ) with its width 11.380,71 ha located in Kecamatan Darul Makmur is widespread in Babah Lueng Village, Kuala Seumayam, Pulo Kruet and Sumber Bakti. In practice, the peat areas in Babah Lueng Village, Kuala Seumayam, Pulo Kruet and Sumber Bakti has been converted by palm plantation and people amongst the plantation area hence the function of the area has been transformed. The research shows that an effort of conserving and reserving the peat ecosystem in Nagan Raya District has not been optimal hence its exploitation is still taking place at the ecosystem and its protection function.

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Journal articles on the topic 'Nagana'

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