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https://www.readbyqxmd.com/read/28727848/the-nuclear-proteome-of-trypanosoma-brucei
#1
Carina Goos, Mario Dejung, Christian J Janzen, Falk Butter, Susanne Kramer
Trypanosoma brucei is a protozoan flagellate that is transmitted by tsetse flies into the mammalian bloodstream. The parasite has a huge impact on human health both directly by causing African sleeping sickness and indirectly, by infecting domestic cattle. The biology of trypanosomes involves some highly unusual, nuclear-localised processes. These include polycistronic transcription without classical promoters initiated from regions defined by histone variants, trans-splicing of all transcripts to the exon of a spliced leader RNA, transcription of some very abundant proteins by RNA polymerase I and antigenic variation, a switch in expression of the cell surface protein variants that allows the parasite to resist the immune system of its mammalian host...
2017: PloS One
https://www.readbyqxmd.com/read/28726862/a-targeted-delivery-strategy-for-the-development-of-potent-trypanocides
#2
Heeren M Gordhan, Jillian E Milanes, Yijian Qiu, Jennifer E Golden, Kenneth A Christensen, James C Morris, Daniel C Whitehead
A new drug delivery strategy was investigated for the development of potent anti-parasitic compounds against Trypanosoma brucei, the causative agent of African sleeping sickness. Thus, potent in vitro hexokinase inhibitors were rendered cytotoxic by appending a tripeptide peroxosomal targeting sequence that facilitated delivery of the molecular cargo to the appropriate organelle in the parasite.
July 20, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28715456/the-trypanosoma-brucei-dihydroxyacetonephosphate-acyltransferase-tbdat-is-dispensable-for-normal-growth-but-important-for-synthesis-of-ether-glycerophospholipids
#3
Rachel Zufferey, Karim Pirani, Melanie Cheung-See-Kit, Sungsu Lee, Tyler A Williams, Daniel G Chen, Md Faruk Hossain
Glycerophospholipids are the most abundant constituents of biological membranes in Trypanosoma brucei, which causes sleeping sickness in humans and nagana in cattle. They are essential cellular components that fulfill various important functions beyond their structural role in biological membranes such as in signal transduction, regulation of membrane trafficking or control of cell cycle progression. Our previous studies have established that the glycerol-3-phosphate acyltransferase TbGAT is dispensable for growth, viability, and ester lipid biosynthesis suggesting the existence of another initial acyltransferase(s)...
2017: PloS One
https://www.readbyqxmd.com/read/28713858/life-stage-specific-cargo-receptors-facilitate-glycosylphosphatidylinositol-anchored-surface-coat-protein-transport-in-trypanosoma-brucei
#4
Emilia K Kruzel, George P Zimmett, James D Bangs
The critical virulence factor of bloodstream-form Trypanosoma brucei is the glycosylphosphatidylinositol (GPI)-anchored variant surface glycoprotein (VSG). Endoplasmic reticulum (ER) exit of VSG is GPI dependent and relies on a discrete subset of COPII machinery (TbSec23.2/TbSec24.1). In other systems, p24 transmembrane adaptor proteins selectively recruit GPI-anchored cargo into nascent COPII vesicles. Trypanosomes have eight putative p24s (TbERP1 to TbERP8) that are constitutively expressed at the mRNA level...
July 2017: MSphere
https://www.readbyqxmd.com/read/28713431/an-unexpected-cause-of-bradycardia-in-a-patient-with-bacterial-meningitis
#5
Petros Ioannou, Magdalini Velegraki, Stella Soundoulounaki, Achilleas Gikas, Diamantis P Kofteridis
Sinus bradycardia which is a sinus rhythm with a resting heart rate of less than 60 bpm is caused by intrinsic cardiac disorders like sick sinus syndrome or inferior myocardial infarction, metabolic and environmental causes (such as hypothyroidism and electrolyte disorders), medications (such as beta-blockers and amiodarone), infection (such as myocarditis), increased intracranial pressure, and toxic exposure, while it can sometimes be a normal phenomenon, especially during sleep, in athletes, and during pregnancy...
2017: Case Reports in Medicine
https://www.readbyqxmd.com/read/28706938/inhibitors-of-glycosomal-protein-import-provide-new-leads-against-trypanosomiasis
#6
COMMENT
Vishal C Kalel, Leonidas Emmanouilidis, Maciej Dawidowski, Wolfgang Schliebs, Michael Sattler, Grzegorz M Popowicz, Ralf Erdmann
Vector-borne trypanosomatid parasite infections in tropical and sub-tropical countries constitute a major threat to humans and livestock. Trypanosoma brucei parasites are transmitted by tsetse fly and lead to African sleeping sickness in humans and Nagana in cattle. In Latin American countries, Trypanosoma cruzi infections spread by triatomine kissing bugs lead to Chagas disease. Various species of Leishmania transmitted to humans by phlebotomine sandflies manifest in a spectrum of diseases termed Leishmaniasis...
July 3, 2017: Microbial Cell
https://www.readbyqxmd.com/read/28684718/steroid-alkaloids-from-holarrhena-africana-with-strong-activity-against-trypanosoma-brucei-rhodesiense
#7
Charles Okeke Nnadi, Ngozi Justina Nwodo, Marcel Kaiser, Reto Brun, Thomas J Schmidt
In our continued search for natural compounds with activity against Trypanosoma brucei, causative agent of human African trypanosomiasis (HAT, "sleeping sickness"), we have investigated extracts from the leaves and bark of the West African Holarrhenaafricana (syn. Holarrhena floribunda; Apocynaceae). The extracts and their alkaloid-enriched fractions displayed promising in vitro activity against bloodstream forms of T. brucei rhodesiense (Tbr; East African HAT). Bioactivity-guided chromatographic fractionation of the alkaloid-rich fractions resulted in the isolation of 17 steroid alkaloids, one nitrogen-free steroid and one alkaloid-like non-steroid...
July 6, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28673422/human-african-trypanosomiasis
#8
REVIEW
Philippe Büscher, Giuliano Cecchi, Vincent Jamonneau, Gerardo Priotto
Human African trypanosomiasis (sleeping sickness) is a parasitic infection that almost invariably progresses to death unless treated. Human African trypanosomiasis caused devastating epidemics during the 20th century. Thanks to sustained and coordinated efforts over the past 15 years, the number of reported cases has fallen to an historically low level. Fewer than 3000 cases were reported in 2015, and the disease is targeted for elimination by WHO. Despite these recent successes, the disease is still endemic in parts of sub-Saharan Africa, where it is a considerable burden on rural communities, most notably in central Africa...
June 30, 2017: Lancet
https://www.readbyqxmd.com/read/28673370/preface-glasgow-encounters-with-tropical-diseases
#9
Francis E G Cox
The period 1875-1925 was remarkable in the history of parasitology mainly for the elucidation of the life cycles of parasites causing important parasitic diseases and the incrimination of vectors in their transmission. These discoveries were made by a small number of scientists working in the tropics a number of whom were Scots. Sir Patrick Manson, the discoverer of the mosquito transmission of filarial worms, was instrumental in directly or indirectly encouraging other Scots including Douglas Argyll-Robertson, David Blacklock, David Bruce, David Cunningham, Robert Leiper, William Leishman, George Low, Muriel Robertson and Ronald Ross, who all made significant discoveries across a wide spectrum of tropical diseases...
July 4, 2017: Parasitology
https://www.readbyqxmd.com/read/28671870/the-double-edged-sword-of-evolution
#10
Etty Kruzel-Davila, Karl Skorecki
Two gene variants provide different levels of protection against sleeping sickness, but this comes with an increased risk of developing chronic kidney disease.
July 3, 2017: ELife
https://www.readbyqxmd.com/read/28668681/targeting-the-active-sites-of-malarial-proteases-for-antimalarial-drug-discovery-approaches-progress-and-challenges
#11
REVIEW
Kuldeep K Roy
Malaria is an infectious disease causing huge mortality and morbidity worldwide. Although antimalarial drugs are effective in several parts of the world, there is a serious threat to malaria control that malaria parasites are continuously developing widespread resistance against currently available antimalarial drugs, including artemisinin. Such widespread antimalarial drug resistance certifies the need of improving the efficacy of existing or new drugs, and developing alternative treatments through the identification of novel drug targets and development of candidate drugs...
June 28, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28642005/expression-purification-and-crystallization-of-type-1-isocitrate-dehydrogenase-from-trypanosoma-brucei-brucei
#12
Xinying Wang, Daniel Ken Inaoka, Tomoo Shiba, Emmanuel Oluwadare Balogun, Stefan Allmann, Yoh-Ichi Watanabe, Michael Boshart, Kiyoshi Kita, Shigeharu Harada
Isocitrate dehydrogenases (IDHs) are metabolic enzymes that catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate. Depending on the electron acceptor and subcellular localization, these enzymes are classified as NADP(+)-dependent IDH1 in the cytosol or peroxisomes, NADP(+)-dependent IDH2 and NAD(+)-dependent IDH3 in mitochondria. Trypanosoma brucei is a protozoan parasite that causes African sleeping sickness in humans and Nagana disease in animals. Here, for the first time, a putative glycosomal T...
June 20, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28637278/functional-and-structural-analysis-of-at-specific-minor-groove-binders-that-disrupt-dna-protein-interactions-and-cause-disintegration-of-the-trypanosoma-brucei-kinetoplast
#13
Cinthia R Millan, Francisco J Acosta-Reyes, Laura Lagartera, Godwin U Ebiloma, Leandro Lemgruber, J Jonathan Nué Martínez, Núria Saperas, Christophe Dardonville, Harry P de Koning, J Lourdes Campos
Trypanosoma brucei, the causative agent of sleeping sickness (Human African Trypanosomiasis, HAT), contains a kinetoplast with the mitochondrial DNA (kDNA), comprising of >70% AT base pairs. This has prompted studies of drugs interacting with AT-rich DNA, such as the N-phenylbenzamide bis(2-aminoimidazoline) derivatives 1 [4-((4,5-dihydro-1H-imidazol-2-yl)amino)-N-(4-((4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)benzamide dihydrochloride] and 2 [N-(3-chloro-4-((4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)-4-((4,5-dihydro-1H-imidazol-2-yl)amino)benzamide] as potential drugs for HAT...
June 16, 2017: Nucleic Acids Research
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
#14
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/28635658/asperentin-b-a-new-inhibitor-of-the-protein-tyrosine-phosphatase-1b
#15
Jutta Wiese, Hülya Aldemir, Rolf Schmaljohann, Tobias A M Gulder, Johannes F Imhoff
In the frame of studies on secondary metabolites produced by fungi from deep-sea environments we have investigated inhibitors of enzymes playing key roles in signaling cascades of biochemical pathways relevant for the treatment of diseases. Here we report on a new inhibitor of the human protein tyrosine phosphatase 1B (PTP1B), a target in the signaling pathway of insulin. A new asperentin analog is produced by an Aspergillussydowii strain isolated from the sediment of the deep Mediterranean Sea. Asperentin B (1) contains an additional phenolic hydroxy function at C-6 and exhibits an IC50 value against PTP1B of 2 μM in vitro, which is six times stronger than the positive control, suramin...
June 21, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28623292/structural-and-biochemical-characterization-of-poly-adp-ribose-polymerase-from-trypanosoma-brucei
#16
Teemu Haikarainen, Mariana Schlesinger, Ezeogo Obaji, Silvia H Fernández Villamil, Lari Lehtiö
Trypanosoma brucei is a unicellular parasite responsible for African trypanosomiasis or sleeping sickness. It contains a single PARP enzyme opposed to many higher eukaryotes, which have numerous PARPs. PARPs are responsible for a post-translational modification, ADP-ribosylation, regulating a multitude of cellular events. T. brucei PARP, like human PARPs-1-3, is activated by DNA binding and it potentially functions in DNA repair processes. Here we characterized activation requirements, structure and subcellular localization of T...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28620452/metabolic-reprogramming-during-the-trypanosoma-brucei-life-cycle
#17
REVIEW
Terry K Smith, Frédéric Bringaud, Derek P Nolan, Luisa M Figueiredo
Cellular metabolic activity is a highly complex, dynamic, regulated process that is influenced by numerous factors, including extracellular environmental signals, nutrient availability and the physiological and developmental status of the cell. The causative agent of sleeping sickness, Trypanosoma brucei, is an exclusively extracellular protozoan parasite that encounters very different extracellular environments during its life cycle within the mammalian host and tsetse fly insect vector. In order to meet these challenges, there are significant alterations in the major energetic and metabolic pathways of these highly adaptable parasites...
2017: F1000Research
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
#18
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 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28605986/perceived-stress-disturbed-sleep-and-cognitive-impairments-in-patients-with-work-related-stress-complaints-a-longitudinal-study
#19
Anita Eskildsen, Hanne Nørr Fentz, Lars Peter Andersen, Anders Degn Pedersen, Simon Bang Kristensen, Johan Hviid Andersen
Patients on sick leave due to work-related stress often present with cognitive impairments as well as sleep disturbances. The aim of this longitudinal study was to examine the role of perceived stress and sleep disturbances in the longitudinal development in cognitive impairments in a group of patients with prolonged work-related stress (N = 60) during a period of 12 months following initial professional care-seeking. Objective cognitive impairments (neuropsychological tests) were measured on two occasions - at initial professional care-seeking and at 12-month follow-up...
June 29, 2017: Stress: the International Journal on the Biology of Stress
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
#20
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
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