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https://www.readbyqxmd.com/read/28636879/delineating-neuroinflammation-parasite-cns-invasion-and-blood-brain-barrier-dysfunction-in-an-experimental-murine-model-of-human-african-trypanosomiasis
#1
Jean Rodgers, Barbara Bradley, Peter G E Kennedy
Although Trypanosoma brucei spp. was first detected by Aldo Castellani in CSF samples taken from sleeping sickness patients over a century ago there is still a great deal of debate surrounding the timing, route and effects of transmigration of the parasite from the blood to the CNS. In this investigation, we have applied contrast-enhance magnetic resonance imaging (MRI) to study the effects of trypanosome infection on the blood-brain barrier (BBB) in the well-established GVR35 mouse model of sleeping sickness...
June 18, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28632168/a-comparative-study-of-the-structural-dynamics-of-four-terminal-uridylyl-transferases
#2
Kevin J Cheng, Özlem Demir, Rommie E Amaro
African trypanosomiasis occurs in 36 countries in sub-Saharan Africa with 10,000 reported cases annually. No definitive remedy is currently available and if left untreated, the disease becomes fatal. Structural and biochemical studies of trypanosomal terminal uridylyl transferases (TUTases) demonstrated their functional role in extensive uridylate insertion/deletion of RNA. Trypanosoma brucei RNA Editing TUTase 1 (TbRET1) is involved in guide RNA 3' end uridylation and maturation, while TbRET2 is responsible for U-insertion at RNA editing sites...
June 20, 2017: Genes
https://www.readbyqxmd.com/read/28628654/the-apah-like-phosphatase-tbalph1-is-the-major-mrna-decapping-enzyme-of-trypanosomes
#3
Susanne Kramer
5'-3' decay is the major mRNA decay pathway in many eukaryotes, including trypanosomes. After deadenylation, mRNAs are decapped by the nudix hydrolase DCP2 of the decapping complex and finally degraded by the 5'-3' exoribonuclease. Uniquely, trypanosomes lack homologues to all subunits of the decapping complex, while deadenylation and 5'-3' degradation are conserved. Here, I show that the parasites use an ApaH-like phosphatase (ALPH1) as their major mRNA decapping enzyme. The protein was recently identified as a novel trypanosome stress granule protein and as involved in mRNA binding...
June 19, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28615873/molecular-characterization-of-internal-transcribed-spacer-1-its-1-region-of-different-trypanosoma-evansi-isolates-of-india
#4
Souti Prasad Sarkhel, Surender Kumar Gupta, Jyoti Kaushik, Jarnail Singh, Deepak Kumar Gaur, Sanjay Kumar, Rajender Kumar
Six Trypanosoma evansi isolates collected from ponies (PH1 and PK6), camel (CB2), donkeys (DJ3 and DH4) and cattle (CK5) from Haryana, Rajasthan, Uttar Pradesh and Gujarat states of India were used for molecular characterization of internal transcribed spacer 1 (ITS 1). The DNA was isolated from purified trypanosomes of these six isolates after propagation in mice model. ITS1-PCR of purified parasite DNA yielded an amplification product approximately 540 bp in size. Nucleotide sequence of ITS1 gene of CB2 isolate had 530 bp while CK5, DH4, DJ3, and PH1 isolates had 532 bp, whereas, PK6 isolates had 533 bp size...
June 2017: Journal of Parasitic Diseases: Official Organ of the Indian Society for Parasitology
https://www.readbyqxmd.com/read/28615858/molecular-diagnosis-of-cattle-trypanosomes-in-venezuela-evidences-of-trypanosoma-evansi-and-trypanosoma-vivax-infections
#5
J R Ramírez-Iglesias, M C Eleizalde, A Reyna-Bello, M Mendoza
In South America Trypanosoma evansi has been determined by molecular methods in cattle from Bolivia, Brazil, Colombia and Peru, reason for which the presence of this parasite is not excluded in Venezuelan livestock. Therefore, the aim of this study was to perform parasitological and molecular diagnosis of cattle trypanosomosis in small livestock units from two regions in this country. The parasitological diagnosis was carried out by MHCT and the molecular by PCR using genus-specific ITS1 primers that differentiate T...
June 2017: Journal of Parasitic Diseases: Official Organ of the Indian Society for Parasitology
https://www.readbyqxmd.com/read/28609481/the-ubiquitin-conjugating-enzyme-cdc34-is-essential-for-cytokinesis-in-contrast-to-putative-subunits-of-a-scf-complex-in-trypanosoma-brucei
#6
Federico Rojas, Joanna Koszela, Jacqueline Búa, Briardo Llorente, Richard Burchmore, Manfred Auer, Jeremy C Mottram, María Teresa Téllez-Iñón
The ubiquitin-proteasome system is a post-translational regulatory pathway for controlling protein stability and activity that underlies many fundamental cellular processes, including cell cycle progression. Target proteins are tagged with ubiquitin molecules through the action of an enzymatic cascade composed of E1 ubiquitin activating enzymes, E2 ubiquitin conjugating enzymes, and E3 ubiquitin ligases. One of the E3 ligases known to be responsible for the ubiquitination of cell cycle regulators in eukaryotes is the SKP1-CUL1-F-box complex (SCFC)...
June 13, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28606317/molecular-occurrence-of-trypanosomes-erythrocyte-and-serum-sialic-acid-concentrations-of-muturu-and-bunaji-cattle-in-benue-state-nigeria
#7
Samuel Ode, Mathew Adamu, Moeti Taioe, Oriel Thekisoe, Sani Adamu, Daniel I Saror
One hundred each, of Muturu and Bunaji cattle were screened, using polymerase chain reaction (PCR), for trypanosomes in Makurdi and Gboko Local Government Areas of Benue State, Nigeria. Erythrocyte surface sialic acid (ESSA) and free serum sialic acid (FSSA) concentrations were determined and compared in both breeds with the aim of providing baseline data for research and diagnostic purposes. Five per cent (5%) and 23% of the Muturu and Bunaji cattle, respectively, were positive for trypanosomes. The result at p=0...
August 15, 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/28596768/african-trypanosomes-undermine-humoral-responses-and-vaccine-development-link-with-inflammatory-responses
#8
REVIEW
Benoit Stijlemans, Magdalena Radwanska, Carl De Trez, Stefan Magez
African trypanosomosis is a debilitating disease of great medical and socioeconomical importance. It is caused by strictly extracellular protozoan parasites capable of infecting all vertebrate classes including human, livestock, and game animals. To survive within their mammalian host, trypanosomes have evolved efficient immune escape mechanisms and manipulate the entire host immune response, including the humoral response. This report provides an overview of how trypanosomes initially trigger and subsequently undermine the development of an effective host antibody response...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28596486/experimental-african-trypanosome-infection-suppresses-the-development-of-multiple-myeloma-in-mice-by-inducing-intrinsic-apoptosis-of-malignant-plasma-cells
#9
Nathan De Beule, Eline Menu, Mathieu Jm Bertrand, Mérédis Favreau, Elke De Bruyne, Ken Maes, Kim De Veirman, Magdalena Radwanska, Afshin Samali, Stefan Magez, Karin Vanderkerken, Carl De Trez
Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells in the bone marrow (BM). Recently, several studies have highlighted the role of pathogens in either promoting or dampening malignancies of unrelated origin. Trypanosoma brucei is an extracellular protozoan parasite which causes sleeping sickness. Our group has previously demonstrated that trypanosome infection affects effector plasma B cells. Therefore, we hypothesized that T. brucei infection could have an impact on MM development...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28586253/characterization-of-recombinant-trypanosoma-brucei-gambiense-translationally-controlled-tumor-protein-rtbgtctp-and-its-interaction-with-glossina-midgut-bacteria
#10
Géraldine Bossard, Manon Bartoli, Marie-Laure Fardeau, Philippe Hozmuller, Bernard Ollivier, Anne Geiger
In humans, sleeping sickness (i.e. Human African Trypanosomiasis) is caused by the protozoan parasites Trypanosoma brucei gambiense (Tbg) in West and Central Africa, and T. b. rhodesiense in East Africa. We previously showed in vitro that Tbg is able to excrete/secrete a large number of proteins, including Translationally Controlled Tumour Protein (TCTP). Moreover, the tctp gene was previously described to be expressed in Tbg-infected flies. Aside from its involvement in diverse cellular processes, we have investigated a possible alternative role within the interactions occurring between the trypanosome parasite, its tsetse fly vector, and the associated midgut bacteria...
June 6, 2017: Gut Microbes
https://www.readbyqxmd.com/read/28573456/backbone-nmr-assignments-of-tryparedoxin-the-central-protein-in-the-hydroperoxide-detoxification-cascade-of-african-trypanosomes-in-the-oxidized-and-reduced-form
#11
Annika Wagner, Erika Diehl, R Luise Krauth-Siegel, Ute A Hellmich
Tryparedoxin (Tpx) is a pivotal protein in the redox-metabolism of trypanosomatid parasites. Tpx has previously been identified as a potential target for drug development in the fight against human African sleeping sickness caused by Trypanosoma brucei. Tpx belongs to the thioredoxin superfamily and acts as an oxidoreductase in the parasite's cytoplasm. It contains a WCPPC active site motif, which enables the protein to undergo thiol-disulfide exchange. To promote future protein-drug interaction analyses, we report the (1)H, (13)C and (15)N backbone chemical shift assignments for both the oxidized and reduced states of Tpx...
June 1, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28567189/polymerase-chain-reaction-identification-of-trypanosoma-brucei-rhodesiense-in-wild-tsetse-flies-from-nkhotakota-wildlife-reserve-malawi
#12
Janelisa Musaya, John Chisi, Edward Senga, Peter Nambala, Emmanuel Maganga, Enock Matovu, John Enyaru
BACKGROUND: Trypanosoma brucei rhodesiense is the causative agent of acute human African trypanosomiasis. Identification of T. b. rhodesiense in tsetse populations is essential for understanding transmission dynamics, assessng human disease risk, and monitoring spatiotemporal trends and impact of control interventions. Accurate detection and characterisation of trypanosomes in vectors relies on molecular techniques. For the first time in Malawi, a molecular technique has been used to detect trypanosomes in tsetse flies in Nkhotakota Wildlife Reserve...
March 2017: Malawi Medical Journal: the Journal of Medical Association of Malawi
https://www.readbyqxmd.com/read/28560059/the-anti-protozoan-drug-nifurtimox-preferentially-inhibits-clonogenic-tumor-cells-under-hypoxic-conditions
#13
Quhuan Li, Qun Lin, Hoon Kim, Zhong Yun
Tumor hypoxia is an independent prognostic indicator of tumor malignant progression and poor patient survival. Therefore, eradication of hypoxic tumor cells is of paramount importance for successful disease control. In this study, we have made a new discovery that nifurtimox, a clinically approved drug to treat Chagas disease caused by the parasitic protozoan trypanosomes, can function as a hypoxia-activated cytotoxin. We have found that nifurtimox preferentially kill clonogenic tumor cells especially under the hypoxic conditions of ≤0...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28552794/front-line-glioblastoma-chemotherapeutic-temozolomide-is-toxic-to-trypanosoma-brucei-and-potently-enhances-melarsoprol-and-eflornithine
#14
Dietmar Steverding, Stuart A Rushworth
Sleeping sickness is an infectious disease that is caused by the protozoan parasite Trypanosoma brucei. The second stage of the disease is characterised by the parasites entering the brain. It is therefore important that sleeping sickness therapies are able to cross the blood-brain barrier. At present, only three medications for chemotherapy of the second stage of the disease are available. As these trypanocides have serious side effects and are difficult to administer, new and safe anti-trypanosomal brain-penetrating drugs are needed...
July 2017: Experimental Parasitology
https://www.readbyqxmd.com/read/28552771/dose-dependent-effect-and-pharmacokinetics-of-fexinidazole-and-its-metabolites-in-a-mouse-model-of-human-african-trypanosomiasis
#15
Hollie Burrell-Saward, Andrew J Harris, Raul de LaFlor, Hatem Sallam, Mo S Alavijeh, Theresa H Ward, Simon L Croft
Human African trypanosomiasis (HAT) is a neglected tropical disease, with a population of 70 million at risk. Current treatment options are limited. In the search for new therapeutics, the repurposing of the broad-spectrum antiprotozoal drug fexinidazole has completed Phase III trials with the anticipation that it will be the first oral treatment for HAT. This study used the recently validated bioluminescence imaging model to assess the dose and rate of kill effect of fexinidazole in infected mice, and the dose-dependent effect of fexinidazole on trypanosome infection...
May 25, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28545671/trypanosuppresive-effects-of-ellagic-acid-and-amelioration-of-the-trypanosome-associated-pathological-features-coupled-with-inhibitory-effects-on-trypanosomal-sialidase-in-vitro-and-in-silico
#16
Raphael Aminu, Mohammed Auwal Ibrahim, Md Atiar Rahman, Raju Dash, Ismaila Alhaji Umar
BACKGROUND: The search for novel antitrypanosomal agents had previously led to the isolation of ellagic acid as a bioactive antitrypanosomal compound using in vitro studies. However, it is not known whether this compound will elicit antitrypanosomal activity in in vivo condition which is usually the next step in the drug discovery process. PURPOSE: Herein, we investigated the in vivo activity of ellagic acid against bloodstream form of Trypanosoma congolense and its ameliorative effects on trypanosome-induced anemia and organ damage as well as inhibitory effects on trypanosomal sialidase...
July 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28542332/non-canonical-binding-interactions-of-the-rna-recognition-motif-rrm-domains-of-p34-protein-modulate-binding-within-the-5s-ribonucleoprotein-particle-5s-rnp
#17
Anyango D Kamina, Noreen Williams
RNA binding proteins are involved in many aspects of RNA metabolism. In Trypanosoma brucei, our laboratory has identified two trypanosome-specific RNA binding proteins P34 and P37 that are involved in the maturation of the 60S subunit during ribosome biogenesis. These proteins are part of the T. brucei 5S ribonucleoprotein particle (5S RNP) and P34 binds to 5S ribosomal RNA (rRNA) and ribosomal protein L5 through its N-terminus and its RNA recognition motif (RRM) domains. We generated truncated P34 proteins to determine these domains' interactions with 5S rRNA and L5...
2017: PloS One
https://www.readbyqxmd.com/read/28541535/genome-wide-snp-analysis-reveals-distinct-origins-of-trypanosoma-evansi-and-trypanosoma-equiperdum
#18
Bart Cuypers, Frederik Van den Broeck, Nick Van Reet, Conor J Meehan, Julien Cauchard, Jonathan M Wilkes, Filip Claes, Bruno Goddeeris, Hadush Birhanu, Jean-Claude Dujardin, Kris Laukens, Philippe Büscher, Stijn Deborggraeve
Trypanosomes cause a variety of diseases in man and domestic animals in Africa, Latin America and Asia. In the Trypanozoon subgenus, Trypanosoma brucei gambiense and T. b. rhodesiense cause human African trypanosomiasis, while T. b. brucei, T. evansi and T. equiperdum are responsible for nagana, surra and dourine in domestic animals, respectively. The genetic relationships between T. evansi and T. equiperdum and other Trypanozoon species remain unclear because the majority of phylogenetic analyses have been based on only a few genes...
May 25, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28537557/apol1-renal-risk-variants-have-contrasting-resistance-and-susceptibility-associations-with-african-trypanosomiasis-renal-risk-variants-have-contrasting-resistance-and-susceptibility-associations-with-african-trypanosomiasis
#19
Anneli Cooper, Hamidou Ilboudo, V Pius Alibu, Sophie Ravel, John Enyaru, William Weir, Harry Noyes, Paul Capewell, Mamadou Camara, Jacqueline Milet, Vincent Jamonneau, Oumou Camara, Enock Matovu, Bruno Bucheton, Annette MacLeod
Reduced susceptibility to infectious disease can increase the frequency of otherwise deleterious alleles. In populations of African ancestry, two apolipoprotein-L1 (APOL1) variants with a recessive kidney disease risk, named G1 and G2, occur at high frequency. APOL1 is a trypanolytic protein that confers innate resistance to most African trypanosomes, but not Trypanosoma brucei rhodesiense or T.b. gambiense, which cause human African trypanosomiasis. In this case-control study we test the prevailing hypothesis that these APOL1 variants reduce trypanosomiasis susceptibility, resulting in their positive selection in sub-Saharan Africa...
May 24, 2017: ELife
https://www.readbyqxmd.com/read/28535252/trypanosome-rna-editing-mediator-complex-proteins-have-distinct-functions-in-grna-utilization
#20
Rachel M Simpson, Andrew E Bruno, Runpu Chen, Kaylen Lott, Brianna L Tylec, Jonathan E Bard, Yijun Sun, Michael J Buck, Laurie K Read
Uridine insertion/deletion RNA editing is an essential process in kinetoplastid parasites whereby mitochondrial mRNAs are modified through the specific insertion and deletion of uridines to generate functional open reading frames, many of which encode components of the mitochondrial respiratory chain. The roles of numerous non-enzymatic editing factors have remained opaque given the limitations of conventional methods to interrogate the order and mechanism by which editing progresses and thus roles of individual proteins...
May 23, 2017: Nucleic Acids Research
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